AAPM Annual Meeting Abstracts

PAIN MEDICINEVolume 6 • Number 2 • 2005

© American Academy of Pain Medicine 1526-2375/05/$15.00/165 165–197

Blackwell Science, LtdOxford, UKPMEPain Medicine1526-2375American Academy of Pain MedicineMarch/April 200562165197Miscellaneous

March/April 200562MiscellaneousAbstractAbstract

ABSTRACTS

AAPM Annual Meeting Abstracts

100Clinical

“Painless” Complex Regional Pain Syndrome, Type I: A Case Report

Brandon Goff, DO, Walter Reed Army Medical Center, Washington, DCLeslie Jackson, MD, Walter Reed Army Medical Center, Washington, DCIntroduction and Statement of the Problem: ComplexRegional Pain Syndrome, Type I (CRPS-I) is a clinicaldiagnosis usually associated with burning pain, hyper-pathia, and allodynia, and often related to trauma ortissue insult that can be distant or seemingly unrelatedto the symptomatic area. It is unusual for a patient topresent with the signs and symptoms of CRPS-I exceptfor pain.Materials and Methods: A patient was referred for thecondition of painless swollen left wrist, hand, andfingers of 6 months’ duration. Chief complaints wereswelling of the fingers and skin tightness of her lefthand. She reported rapid left fingernail growth, and theskin of her left hand was shiny and often changed colorswithin the course of a day (photos 1, 2). Onset of symp-toms closely followed two falls onto her left arm andshoulder. Initial laboratory and radiographic evaluationwas negative (radiograph 1). Subsequent radiographsafter 3 months revealed significant generalizedosteoporosis, a lacey trabecular pattern of the proximalphalanges, and resorption of the medial aspects of thedistal ends of both the proximal and middle phalanges(radiograph 2). Three-phase bone scanning revealedincreased asymmetric flow and increased periarticularuptake in the wrist and hand (scan 1).Results: The clinical picture was consistent withCRPS-I [1]. A comprehensive, multidisciplinary treat-ment plan was prescribed and her symptoms wereresolved [2].Conclusions: The lack of pain as a presenting symptommade this case an interesting diagnostic and therapeuticchallenge [3]. Very few cases of painless CRPS-I havebeen reported, and the incidence and prevalence isunknown. It is not uncommon for patients with CRPS-I to have prolonged and refractory courses, incurringchronic disabilities related to pain. We remind clini-

cians to remain vigilant for painless CRPS-I because thesame constellation of symptoms and signs may alsopresent without pain.

References

1 Stanton-Hicks M. Complex regional pain syndrome.Anesthesiol Clin North America 2003;21(4):733–44.

2 Ribbers GM. Pharmacologic treatment of complexregional pain syndrome I: A conceptual framework.Arch Phys Med Rehabil 2003;84(1):141–6.

3 Eisenberg E, Melamed E. Can complex regional painsyndrome be painless? Pain 2003;106(3):263–7.


101Clinical

Memantine, a Treatment for Migraine: A Prospective Open-Label Trial

Raymond Sorensen, DO, PETC Research Group, Inc., Tulsa, OKMichael Jenson, MS, PETC Research Group, Inc., Tulsa, OKWe evaluated the use of a new N-methyl-d-aspartate(NMDA) antagonist, Memantine (Namenda®), in 18consecutive patients (4 males, 14 females) with migraine(age 36–67). All were refractory to beta-blockers,calcium channel blockers, opiates, ergot alkaloids,naratriptan, gabapentin, and zolmitriptan, and two hadbeen refractory to tiagabine and carbamazepine. A cen-tral sensitization has been advocated to explain chronicdaily congenital dislocation of the hip (CDH) due tosustained peripheral sensitization of allogenic structuresresponsible for sustained trigeminovascular systemactivation. They involve NMDA receptor activationand nitric oxide production and hypersensitivity andincreased and maintained production of sensory neu-ropeptides. Memantine is FDA approved and has beendemonstrated to be safe and effective in the symptom-atic treatment of Alzheimer’s disease. NMDA receptorsappear to be a key target of memantine at therapeuticconcentrations. Memantine is an uncompetitive (chan-nel blocking) NMDA receptor antagonist [1]. Patientswere started on 5 mg of memantine daily for 1 week,

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then 5 mg bid for 1 week, then 10 mg in the am and5 mg in the pm for 1 week then 10 mg bid. Patientinterview, examination, and the McGill short-form painquestionnaire was used to grade responses. Responseswere characterized as follows: excellent (greater than70% reduction in headache), good (50–70% improve-ment), fair (20–50% improvement), and poor (less than20% improvement). The following results wereobtained: 11 excellent, 4 good, 2 fair, and 1 poor. Twopatients had a moderate adverse event (one had dizzi-ness, and the second had mild depression), though theyhad an excellent response. Treatment for only onepatient was discontinued before the 10 mg bid dose wasattained. Memantine is a most promising medication inthe treatment of migraine. The 18 cases reflect a needfor further investigation of memantine in the form ofdouble-blind placebo-controlled studies.

Reference

1 Rogawski MA, Wenk GL. The neuropharmacologi-cal basis for the use of memantine in the treatmentof Alzheimer’s disease. CNS Drug Rev 2003;9(3):275–308.


102Clinical

An Open-Label Trial of Tiagabine in Patients with Primary Fibromyalgia Syndrome

Raymond Sorensen, DO, PETC Research Group, Inc., Tulsa, OKIntroduction: We evaluated the use of Tiagabine(Gabitril®), an anticonvulsant, in patients with PrimaryFibomyalgia Syndrome (PFS). PFS is a chronic paincondition characterized by a diffuse pain pattern overthe entire body. Tiagabine (TGB) increases synapticgamma-aminobutyric acid (GABA) availability by bind-ing reversibly and saturably to recognition sites associ-ated with GABA transporter protein in neuronal andglial membranes [1].Methods: Consecutive patients with PFS who werenonresponders to opiates, nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepres-sants, and gabapentin were enrolled. TGB therapy wasinitiated at 4 mg qhs as add-on therapy to the patient’scurrent medication regimen. TGB was increased every3–5 days by 4 mg to 8 mg qhs to a maximum of 12 mg/day. The following outcome measures were evaluated:McGill Short-Form Pain Questionnaire, numeric painscore, patient and physician subjective global response,examination for degree of tenderness. Patients were fol-lowed monthly. Adverse events were noted.

Results: A total of 11 patients (10 women, 1 man) withPFS were given TGB. Mean age was 46 years (range:31–59). At final outcome measurement, 64% of thepatients had received TGB for 12 months (range: 1–12 months) and mean Numeric Pain score decreasedfrom 8.3 (range: 7–10) to 3.7 (range: 0–10) and meanMcGill decreased from 38.4 (range: 32–44) to 17.3(range: 0–30). Patient responses were as follows:excellent = 6 (55%); good = 1 (9 %); fair = 3 (27%); andpoor = 1 (9 %). Adverse events were reported by onepatient (nausea and sedation). Two patients discon-tinued treatment; one patient for poor response andone patient due to adverse events.Conclusions: Overall, TGB was well-tolerated anddemonstrated an effective response to this very-difficult-to-treat condition. The eleven cases reflect aneed for further investigation of TGB in the form ofdouble-blind placebo-controlled studies.

Reference

1 Suzdak PD, Jansen JA. A review of the preclinicalpharmacology of tiagabine: A potent and selectiveanticonvulsant GABA uptake inhibitor. Epilepsia1995;36:612–26.


103Clinical

Weaning Off High Doses of Opioids for Analgesia without Side Effects with Short-Term Neuraxial Anesthesia and Opioid Rotation to Methadone

Nalini Vadivelu, MD, Yale University, New Haven, CTJessica Feinleib, MD, Yale University, New Haven, CTErin Kong, MD, Yale University, New Haven, CTKatherine Marschall, MD, Yale University, New Haven, CTIntroduction: Weaning of a patient being treated forpain from opioids and the detoxification of a patientbeing treated for drug addiction are considered distinctactivities under the Controlled Substances Act (CSA) of1970 and its implementing regulations. We present aninteresting case where we were able to successfully weana patient off greater than 10,000 oral morphine equiv-alents per day given for analgesia to fewer than 200 mgof oral morphine equivalents per day.Methods: A 48-year-old female with a history of met-astatic leiomyosarcoms to the lumbosacral spine wasadmitted for removal of the tumor. Her medications forintractable pain upon transfer were morphine 85 mg/hour, hydromorphone 10 mg/hour, vioxx 25 mg perday, ellaville 150 mg per day and fentanyl 300 mg perhour patches. Intraoperatively a tunneled epidural wasplaced and intravenous sufentanil was used. Postopera-

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tively the patient was given an epidural infusion of 50 mgof hydromorphone per milliliter and bupivacaine0.031% at 5 mL per hour for 2 days and hydromor-phone intravenously at 15 mg per hour with availableprn doses and methadone elixir hydromorphone wastitrated down. The patient was discharged on the sixthpostoperative day with methadone elixir 40 mg po tidand actiq lozenges 200 mg prn, vioxx 25 mg per day andelavil 40 mg q hs with good pain control and no with-drawal symptoms throughout.Discussion: There is little information on the weaningprocess for patients prescribed very high doses of opi-oids >1,000 mg of oral morphine equivalents for anal-gesia. There are no previous reports of weaningprocesses for patients prescribed >10,000 mg of mor-phine equivalents for analgesia.

Reference

1 Portenoy RK. Opioid therapy for chronic non-malignant pain: A review of the critical issues. J PainSymptom Manage 1996;11(4):203–17.


104Clinical

Efficacy of Topical Lidocaine 5% Patch in Musculoskeletal and Neurological Pain—A Retrospective Case Series

Laura Hobart, BS, BA, The Pain Management Institute, Overland Park, KSSrinivas Nalamachu, MD, The Pain Management Institute, Overland Park, KSThe Lidoderm patch, which consists of 5% topicallidocaine, is FDA approved for and has been used withsuccess in patients with neuropathic pain associatedwith postherpetic neuralgia. The patch is formulated todeliver lidocaine to the peripheral sites of applicationwith minimal systemic levels, making it ideal for local-ized pain, while reducing risk of systemic adverse eventsor drug–drug interactions. Randomized controlled clin-ical trials have shown that patients with postherpeticneuralgia report a significant decrease in pain intensityand allodynia when using the lidocaine patch.

Because of its demonstrated efficacy with intensepostherpetic neuralgia pain, we have used it for multiplemusculoskeletal and neurological conditions as symp-tomatic treatment for localized pain relief. In our prac-tice, we have found the patch to be useful for back andneck pain, tendonitis and bursitis, as well as entrapmentneuropathies, such as carpal tunnel syndrome, cubitaltunnel syndrome, and meralgia paresthetica. As thepatch can be cut to any size, it is remarkably versatile

and may be applied to virtually any area of the body,provided the skin is intact.

We conducted a retrospective, single-center study of14 patients with pain secondary to entrapment neurop-athy, tendonitis, or bursitis. Of the 14 patients, 12 werefemale, and the average age was 46 with ages rangingfrom 25 to 81 years. Eighty-two percent of patientsreported significant improvement over baseline symp-toms, the average improvement being 44%. Even thosepatients who were previously on opioid analgesics suchas Oxycodone and Propoxyphene reported a significantimprovement in their symptoms after the addition ofthe Lidoderm patch, 65% on average. These resultssuggest that Lidoderm is an effective treatment of thepain associated with entrapment neuropathies, tendoni-tis, and bursitis. It potentially decreases the need fororal medications and injections. Further studies arewarranted.

References

1 Katz NP. Lidocaine patch 5% reduces pain intensityand interference with quality of life in patients withpostherpetic neuralgia: An effectiveness trial. PainMed 2002;3(4):324–32.

2 Galer BS. The lidocaine patch 5% effectively treatsall neuropathic pain qualities: Results of a random-ized, double-blind, vehicle-controlled, 3-week effi-cacy study with use of the neuropathic pain scale.Clin J Pain 2002;18(5):297–301.


105Clinical

Peripheral Nerve Stimulation for Postsurgical Facial Neuralgias

Salim Hayek, MD, PhD, Cleveland Clinic Foundation, Cleveland, OHJaimie Henderson, MD, Stanford University School of Medicine, Palo Alto, CANicholas Boulis, MD, Cleveland Clinic Foundation, Cleveland, OHLeonardo Kapural, MD, PhD, Cleveland Clinic Foundation, Cleveland, OHMichael Stanton-Hicks, MD, Cleveland Clinic Foundation, Cleveland, OHMekhail Nagy, MD, PhD, Cleveland Clinic Foundation, Cleveland, OHWe report three cases of refractory chronic postsurgicaltrigeminal neuropathic pain that were successfullytreated with peripheral nerve stimulation using percu-taneous leads. One patient had supraorbital neuralgiaand two patients had infraorbital neuralgia. Two of thepatients developed the pain following multiple sinus

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surgeries and one following extensive facial reconstruc-tion secondary to basal cell carcinoma. All patientsresponded with short-term pain relief to blocks of therespective peripheral branches of the trigeminal nerve(supraorbital and infraorbital nerve blocks). However,they failed other interventions including conservativemedical management, acupuncture, and radiofrequencyablation. All patients had successful extended peripheralnerve stimulation trials and subsequently underwentpermanent implantation with percutaneous leads placedin proximity of the supraorbital or infraorbital nerve.Follow-up over 2 months after implantation revealedsignificant decreases in visual analog scale pain scoresand drastic improvement in functional capacity in allthree patients. In this report, we describe the techniqueand its advantages.

References

1 Burchiel KJ. A new classification for facial pain.Neurosurgery 2003;53(5):1164–6.

2 Dunteman E. Peripheral nerve stimulation for unre-mitting ophthalmic postherpetic neuralgia. Neuro-modulation 2002;51:32–7.

3 Pollard CA. Preliminary validity study of the paindisability index. Percept Motor Skills 1984;59:974.


106Clinical

ISPR: A Web-Based Implantable Systems Performance Registry

Lisa Stearns, MD, Valley Pain Treatment Center, Scottsdale, AZLiesl Hargens, Medtronic Neurological, Minneapolis, MNValerie Stoker, MPH, Medtronic Neurological, Minneapolis, MNTodd Weaver, PhD, MPH, Medtronic Neurological, Minneapolis, MNIntroduction: The Implantable Systems PerformanceRegistry (ISPR) is an ongoing, prospective, multicenterpostmarket surveillance registry developed as a follow-up to a fax-based registry, the National OutcomesRegistry for Low Back Pain [1,2]. ISPR is designed tomonitor U.S. Medtronic infusion and neurostimulationsystems. The objectives of ISPR include ongoing prod-uct evaluation with the goal of improving quality andreliability; longitudinal analyses evaluating implant andpractice techniques; and patient and device outcomestracking. The publication and reporting strategy forISPR is overseen by a multispecialty advisory board.Methods: ISPR centers follow standard clinical practiceand a common registry protocol. ISPR collects registry

data through a secure Web-based system, which enableselectronic data capture (EDC) from each center. Infor-mation registered with the FDA-required Device Reg-istration System (DRS) is automatically loaded intoISPR and electronic action items are generated. Thesealerts prompt the center to submit electronic data undervarious categories including enrolling a patient, enroll-ing a device, and providing a patient status update at 6-month intervals. The center reports events such as thoserequiring surgical intervention, patient death, and lost tofollow-up. FDA-required Medical Device Reporting(MDR) is completed through an automatic notificationprocess for qualifying events. The prepopulation ofISPR with previously entered information and automaticnotification processes are key design advantages.Results: Within the first 8 months of operation, tencenters actively contributed data for 509 enrolledpatients with implantable systems. The intent of thispresentation is to describe the methodology and presentpreliminary results.Conclusions: This prospective clinical registry collectscomprehensive information and long-term outcomesrelated to system performance. We will utilize data toimprove products and guide development toward thegoal of better patient outcomes. This registry will serveas a foundation and electronic platform for future out-come registry projects.

References

1 Deer T, Chapple I, Classen A, et al. Intrathecal drugdelivery for treatment of chronic low back pain:Report from the national outcomes registry for lowback pain. Pain Med 2004;5(1):6–13.

2 Gallagher RM. Intrathecal drug delivery for chronicback pain: Better science for clinical innovation. PainMed 2004;5(1):1–3.

Funding: Medtronic, Inc.March/April 200562MiscellaneousAbstractAbstract

107Clinical

Treatment of Refractory Low Back Pain with Botulinum Toxin A: A Prospective 14-Month Study

Bahman Jabbari, MD, Yale University School of Medicine, New Haven, CTMarc Difazio, MD, Walter Reed Medical Center, Washington, DCJohn Ney, MD, Walter Reed Medical Center, Washington, DCA previous short-term, randomized, double-blind studysuggested efficacy of botulinum toxin A (BoNT-A) inchronic low back pain [1]. We have prospectively inves-

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tigated the effect of BoNT-A on chronic, refractory lowback pain (crLBP) of 75 adults. The cohort’s mean agewas 46 years (range 19–72). The patients receivedBoNT-A (100 u/CC) into paraspinal muscles at baselineand when the pain recurred, usually at 4, 8, and12 months. BoNT-A was administered into three to fiveparaspinal levels on each side (50 units/site), as close aspossible to the tender points. The total dose per sessionvaried from 200 to 450 units (mean 285) depending onthe pain extension and laterality. The pain characteristicsand patient’s functional limitations were recorded viavisual analog scale (VAS), Oswestory Low Back PainQuestionnaire (OPQ) and Pain Impact Questionnaire(PIQ), at baseline, 3 weeks, 2, 4, 6, 8, 10, 12, and14 months. They also had a neurological examinationand recorded inquiry of side effects at these intervals.Patients did not change their physical therapy programor pain medications during the period of the study. Asignificant response to pain and significant functionalimprovement were noted in 56 and 54% of the patientsat 3 weeks and 2 months after first treatment (P < 0.05).There was no difference between responders and non-responders as to age, pain intensity, duration, laterality,and history of previous surgery. Responders continuedto respond (90%) to subsequent treatments. Twopatients had a transient flu reaction and one patientexperienced 60 seconds of acute root pain after injection.Conclusion: A subset of patients with crLBP respondwell to BoNT-A treatment of paraspinal muscles. Initialresponsiveness predicts later responsiveness. Sideeffects are transient and uncommon.

Reference

1 Foster L, Clapp L, Erickson M, Jabbari B. Botulinumtoxin A and chronic low back pain. A randomized,double blind study. Neurology 2001;56:1290–3.

Funding: Allergan Inc.March/April 200562MiscellaneousAbstractAbstract

108Clinical

Effect of Demographic Factors and Outcomes on KADIAN® Once- or Twice-Daily Dosing

Arnold Weil, MD, Non-Surgical Orthopedic & Spine Center, PC, Marietta, GAJohn Sasaki, MD, Casa Colina Rehabilitation Center, Pomona, CABruce Nicholson, MD, Pain Specialist of Greater Lehigh Valley, Allentown, PAEdgar Ross, MD, Brigham and Women’s Hospital, Boston, MAIntroduction: The KADIAN® formulation of sus-tained-release morphine sulfate is indicated for either

once-daily (QD) or twice-daily (BID) dosing forpatients with moderate-to-severe chronic pain. Littleinformation is available regarding factors determiningwhether patients are likely to dose QD versus BID. Thisanalysis was designed to identify demographic factorsor outcomes that may influence the choice of QD versusBID dosing in patients with chronic nonmalignant pain(CNMP).Materials and Methods: The KRONUS-MSP Trial 1randomized patients with moderate-to-severe CNMP(N = 1,428) to QD KADIAN, dosed either am or pm.At week 2, investigators could switch to BID dosing ifindicated. At week 4, changes in pain intensity, sleepquality, global patient satisfaction, and quality of life(SF-36v2 Health Survey2) were evaluated. Data wereanalyzed with respect to demographic factors and treat-ment outcomes.Results: By week 4 (N = 1,072), 55% of patientswere on QD dosing, and 45% were on BID dosing(P = 0.0004). Of the patients >65 years, 71%remained on QD dosing; 56% of those £65 yearsremained on QD dosing. The mean total daily dosewas lower in patients dosing QD versus BID (59 mgvs 127 mg for patients >65 years; 81 mg vs 137 mgfor patients £65 years). Men and women remainedon QD dosing with similar frequency, as did AfricanAmericans and Caucasians. Efficacy outcomes (painintensity, sleep, patient satisfaction, and SF-36v2scores) and tolerability were similar between QD andBID dosing groups.Conclusions: KADIAN, whether dosed QD or BID,was effective and well tolerated in relieving CNMP.Patients >65 years were more often treated QD andwith lower doses when compared with younger patients.Overall, patients requiring higher doses of KADIANwere more likely to dose BID; however, tolerabilityremained similar between the QD and BID dosinggroups.

References

1 Ross E, Sasaki J, Weil A, Nicholson B. KADIAN®(morphine sulfate sustained release capsules)improves quality of life in patients with chronic, non-malignant, moderate/severe pain: Efficacy, tolerabil-ity, and safety results from the KRONUS-MSP trial[poster]. Poster presented at: American Academy ofPain Medicine 20th-Annual Meeting; March 3–7,2004, Orlando, FL.

2 Ware JE, Kosinski M, Dewey JE. How to score ver-sion 2 of the SF-36® health survey. Lincoln, RI:Quality Metric Incorporated; 2000.

Funding: Alpharma U.S. Pharmaceuticals BrandedProducts Division.March/April 200562MiscellaneousAbstractAbstract

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110Clinical

Efficacy of Sciatic Nerve Block in Relieving Pain Following Achilles Tendon Repair: A Case Report

Andrew Barker, DO, LUMC/Hines VA, Chicago, ILRaj Uppal, MD, Hines VA Hospital, Maywood, ILSetting: VA Hospital Pain Clinic.Patient: Fifty-year-old male status post Achilles tendondebridement and repair.Case Description: The patient sustained an Achillestendon partial tear while on active duty. Conservativemeasures to allow the tendon to heal, including physicaltherapy, a cam walker, heel lifts, and nonsteroidal anti-inflammatory drugs (NSAIDs) failed. The patient’s painprogressed over the next year, when he opted for surgi-cal repair. After surgical debridement and repair, thepatient was in a cast for 6 weeks. Aggressive physicaltherapy was prescribed; however, he was unable to fullyparticipate because of pain (VAS 8/10), and made nosignificant progress.Intervention: Using a 4-inch stimuplex needle and anerve stimulator, area of sciatic nerve was identified atthe infragluteal area. A total of 30 mL mepivacaine1.5% and bupivacaine 0.5% with epi 1 : 200,000 wasinjected in incremental doses of 3 mL each after ascer-taining negative aspiration for blood.Assessment/Results: The patient’s pain was signifi-cantly reduced following this procedure (VAS 1/10),and he was able to fully participate in physical therapy.While the therapy was limited initially by paralysis fol-lowing the procedure, his range of motion and func-tional ability improved dramatically.Discussion: The sciatic nerve block was used to reducethe patient’s pain and eliminated the patient’s apprehen-sion regarding the use of his right foot.Conclusion: Sciatic nerve block produced excellent painrelief and allowed this patient to progress through hisphysical therapy with confidence in his surgicallyrepaired tendon. Further studies are warranted to eval-uate the efficacy of sciatic nerve block in aggressiverange of motion therapy to advance the functionalcapacity in patients following Achilles tendon repair.

References

1 Prithvi Raj P. Pain medicine: A comprehensivereview. 2nd edition.

2 Casazza B, et al. Musculoskeletal disorders of thelower limbs.

3 di Benedetto P, Casati A, Bertini L, Fanelli G, ChellyJE. Postoperative analgesia with continuous sciaticnerve block after foot surgery: Prospective, random-ized comparison between popliteal and subglutealapproaches. Anesth Analg 2002;94(4):996–1000.


111Clinical

Intrathecal Ziconotide for Chronic, Severe Pain: A Case Study

Robert Fisher, MD, RC, Goodman Institute for Pain Management, Sparks Ambulatory Surgery Center, Fort Smith, ARKristi Lokey, LPN, CCRC, RC, Goodman Institute for Pain Management, Sparks Ambulatory Surgery Center, Fort Smith, ARIntroduction: Ziconotide is an intrathecally adminis-tered nonopioid analgesic for treating severe, chronicpain. This report describes a patient receivingziconotide for post-traumatic pain.Materials and Methods: This 16-year-old male withreflex sympathetic dystrophy in both lower extremitiesexperienced chronic, burning pain, partial loss of prop-rioception in the feet, photophobia, sensitivity totouch and temperature changes, and antalgic gait. HisVisual Analog Scale of Pain Intensity (VASPI) scoresranged from 70 to 100 mm. He received multipleunsuccessful oral medication trials, physical therapy,and a lumbar sympathetic block procedure. He begana ziconotide trial at 5 mcg/day with a surgicallyimplanted pump.Results: Five days after ziconotide initiation (dosage,6 mcg/day), the pump was stopped due to urinaryretention, which later resolved. Approximately 1 weeklater, ziconotide was reinitiated at 2.5 mcg/day. Atweek 6 (dosage, 5.5 mcg/day), the patient’s walkingability improved. By week 8 (dosage, 6.5 mcg/day), hiscondition improved substantially. Ziconotide wastitrated to 7.5 mcg/day over 1 year. At month 6, hebecame sedentary and depressed and received ven-lafaxine, which improved his emotional state withoutaffecting VASPI scores. Late in month 7, his gait wasnormal, and his activity level increased. His ziconotidedosage was decreased to 4.5 mcg/day by the end ofyear 2. His activity level returned to normal; he grad-uated from high school, worked full time, and partici-pated in sports. By late in year 3, he reportedcomplete pain cessation, enrolled in college, becameengaged, and discontinued all oral medications. Hisdosage was reduced to 1.151 mcg/day. His VASPIscores range from 0 to 10 mm. Because of increasedwork-related activity, he titrated to a dosage of2.8 mcg/day and has sustained high quality of life onziconotide monotherapy.Conclusions: This report describes successfulziconotide monotherapy. The patient experiencedquality-of-life improvements and remains pain free.

Funding: Elan Pharmaceuticals.March/April 200562MiscellaneousAbstractAbstract

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112Clinical

An Iontophoretic Fentanyl HCl Patient-Controlled Transdermal System (PCTS) Versus Intravenous Patient-Controlled Morphine for the Treatment of Acute Postoperative Pain after General Surgery

Shireen Ahmad, MD, Northwestern University Feinberg School of Medicine, Chicago, ILDavid Hewitt, MD, Ortho-McNeil Pharmaceutical, Raritan, NJShu-Chen Wu, PhD, Ortho-McNeill Pharmaceutical, Raritan, NJIntroduction: A noninvasive, preprogrammed, creditcard-sized, iontophoretic, fentanyl HCl patient-controlled transdermal system (PCTS) is in develop-ment for the treatment of acute postoperative pain. Inthis setting, administration of morphine via intravenouspatient-controlled analgesia (IV PCA) devices is com-mon. A large (N = 636), randomized, multicenter study,which included a variety of surgery types, found the twoapproaches to be therapeutically equivalent. This suba-nalysis of that study compared their safety and efficacyin the subset of patients who had undergone generalsurgery.Methods: Adult patients were titrated to comfort withopioids after major surgery and randomized 1 : 1 to thefentanyl PCTS or IV PCA morphine. The subset ofgeneral surgery patients contained 53 patients in thePCTS group and 58 patients in the morphine IV PCAgroup. The fentanyl PCTS delivered 40 mg fentanyl, upto 6 doses/hour. IV PCA delivered 1 mg morphine, upto 10 mg/hour. Pain intensity scores, measured by thevisual analog scale (VAS), were recorded before ran-domization and thereafter for 72 hours. The primaryefficacy end point was the proportion of patients ratingtheir method of pain control as excellent or good (versusfair or poor) during the first 24 hours (patient globalassessment, PGA).Results: PGA was comparable between groups, with44/53 (83.0%) patients receiving the fentanyl PCTSrating their pain control method as excellent or good,compared with 46/58 (79.3%) receiving morphine IVPCA (difference = 3.7%; 95% CI, -10.8%, 18.2%;P = 0.618). Pain intensity scores at 24 hours were 21.5for PCTS and 21.6 for IV PCA (P = 0.994); between-group scores were similar at all measured time points.The most frequent treatment-related adverse events inboth groups were nausea, pruritus, and vomiting.Conclusions: In patients who had undergone generalsurgery, the fentanyl HCl PCTS was comparable inefficacy to a standard regimen of morphine IV PCA forpostoperative pain control.

Reference

1 Viscusi ER, Reynolds L, Chung F, Atkinson LE,Khanna S. Patient-controlled transdermal fentanylhydrochloride vs. intravenous morphine pump forpostoperative pain. JAMA 2004;291:1333–41.

Funding: Johnson & Johnson Pharmaceutical Researchand Development.March/April 200562MiscellaneousAbstractAbstract

114Clinical

Spinal Cord Stimulation May Be an Effective Treatment for Severe Visceral Pelvic Pain

Leonardo Kapural, MD, PhD, Cleveland Clinic Foundation, Cleveland, OHNagy Mekhail, MD, PhD, Cleveland Clinic Foundation, Cleveland, OHRecent studies have demonstrated significant involve-ment of dorsal column pathways in transmission ofvisceral pelvic pain [1]. Spinal cord stimulation (SCS)suppresses visceral response to colon distension in ananimal models [2] and therefore may be an effectivetherapy for chronic pelvic pain of visceral origin. Weare reporting on the effectiveness of neurostimulationfor chronic visceral pelvic pain in five female patientswith the diagnosis of long-standing pelvic pain, historyof endometriosis, multiple surgical explorations, anddyspareunia. They all received repeated hypogastricblocks (in an average of 5.3 blocks) with full pain relieffrom 1 to 4 weeks. Two received neurolytic hypogastricblock with the pain relief of 3 and 8 months, respec-tively. Following psychological evaluation and clearanceby our Committee on Implantable Devices they allunderwent SCS trial from 7 to 14 days. Implanted weretypically two Compact (Medtronic Inc, Minneapolis,MN) leads with the electrode tip most commonly atT12-L1 level and the generator. The average follow-upwas 33.6 months. Median VAS pain score decreasedfrom 8 to 3. All patients had more than 50% of the painrelief. Pain Disability Index (PDI) [3] changed from anaverage of 58 to 19.7. Opioid use decreased from anaverage 26 mg to 5 mg of MSO4 equivalent per day.There were two revisions, both for lead migration, butif calculated per years of SCS use, it came to about onerevision per 7 years of stimulation. It appears that SCSmay have a significant therapeutic potential for thetreatment of visceral pelvic pain.

References

1 Palacek J, Wilis WD. The dorsal column pathwayfacilitates visceromotor responses to colorectaldistention after colon inflammation in rats. Pain2003;104:501–7.

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2 Greenwood-Van Meerveld B, Johnson AC, ForemanRD, Linderoth B. Attenuation by spinal cord stimu-lation of a nonciceptive reflex generated by colorectaldistention in a rat model. Auton Neurosci2003;104:17–24.

3 Pollard CA. Preliminary validity study of the paindisability index. Percept Mot Skills 1984;59:974.


119Clinical

Canadian Pain Study II: Profile of Chronic Noncancer Pain in Canada, 2004

Pamela L. Squire, MD, Lions Gate Hospital, Vancouver, British Columbia, CanadaAlexander J. Clark, MD, Calgary Health Region, Calgary, Alberta, CanadaAline Boulanger, MD, Hotel-Dieu du CHUM, University of Montreal, Montreal, Quebec, CanadaG. L. A. Horbay, PhD, Janssen-Ortho Inc., Toronto, Ontario, CanadaEdward Cui, MBA, Janssen-Ortho Inc., Toronto, Ontario, CanadaIntroduction: In a 2001 survey, Morley-Forster et al.(2003) showed that general practitioners who prescribeanalgesics >20 times per month see an average of 45patients/month (range 4–200) with moderate-to-severechronic pain (38 suffering chronic noncancer pain(CNCP)) [1]. The objective of the current study was tore-evaluate this prevalence in primary care practice, andto compare to the 2001 data.Methods: To assess the current profile of Canadianpatients with CNCP, an in-depth telephone survey wasconducted, interviewing a nationally representative tar-geted sample of 100 family physicians, all writing >20analgesic prescriptions/week for CNCP. Chronic painwas defined as pain of >6 month’s duration.Results: Of all patients seen for chronic pain, the phy-sicians surveyed estimated that 85% had CNCP and15% suffered from cancer pain, versus 83% and 17%,respectively, in 2001. Of CNCP patients, 67% havemoderate-to-severe pain levels; this is unchanged from2001 (65%). Pain causation is attributed primarily toarthritis (31%), lower back/spinal conditions (21%),injury/postoperative state (13%), migraine/headacheand neuropathic/neurological disease (both 11%). In19% of CNCP patients, no etiology is obvious. Patientscomplain to physicians primarily of back pain (95% vs81% in 2001; P = 0.05), knee pain (49% vs 39%;P = 0.17), neck pain (37% vs 43%; P = 0.44), and headpain/headache (36% vs 46%; P = 0.2). On average, phy-sicians surveyed see 58 patients/month for moderate-to-severe CNCP (range 5–300), and write an average of

57 analgesic prescriptions/month; an average of 16% ofthe chronic pain patients were new to the physician’spractice. Patients with moderate-to-severe CNCP visittheir family physician’s office a median of 10 times peryear, primarily because of pain.Conclusions: More than two-thirds of CNCP patientsseen by family physicians have moderate-to-severe pain.Back pain predominates and is increased in frequencyover 2001; pain is responsible for frequent visits to thefamily physician’s office.

Reference

1 Morley-Forster PK, et al. Attitudes toward opiate usefor chronic pain: A Canadian physician survey. PainRes Man 2003;8(4):189–94.

Funding: Janssen-Ortho Inc, Canada.March/April 200562MiscellaneousAbstractAbstract

120Clinical

Efficacy and Safety of Kadian® in the Treatment of Neuropathic Pain

John Sasaki, MD, Casa Colina Rehabilitation Center, Pomona, CABruce Nicholson, MD, Pain Specialist of Greater Lehigh Valley, Allentown, PAArnold Weil, MD, Non-Surgical Orthopedic & Spine Center, PC, Marietta, GAEdgar Ross, MD, Brigham and Women’s Hospital, Boston, MAIntroduction: Pain due to lesions of the peripheral and/or central nervous system is heterogeneous in etiologyand clinical presentation [1]. This study evaluated theeffectiveness of the Kadian formulation of sustained-release morphine sulfate in treating neuropathic painamong patients with inadequate treatment outcome(pain rating of ≥4 on a scale of 0–10) on other painmedications, mostly opioids.Methods: The KRONUS-MSP (Kadian: Response ofNonmalignant, Undertreated Subjects with Moderate/Severe Pain) trial was a prospective study yielding alarge (N = 1,428) database of patients treating chronicnonmalignant pain with Kadian. Based on baseline pri-mary diagnosis, patients were classified into two paingroups—presumptive neuropathic pain (PNP) or allother pain (AOP). Efficacy outcomes included painintensity (0–10 scale), sleep quality (0–10 scale), globalpatient and physician therapy assessments (-4 to +4scale), and quality of life (QoL; SF-36v2(tm) data [2]).Changes from baseline to week 4 were evaluated.Results: Data were available for 1138 intent-to-treatpatients, 498 with PNP. There were no significant dif-

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ferences in demographics or efficacy outcomes betweenPNP and AOP groups. Among patients with PNP, thedecrease from baseline to week 4 in pain scores wasfrom 7.6 to 5.1; sleep scores were reduced from 6.3 to4.3. Patient global assessment increased from -1.3 atbaseline to +1.2 at week 4; physician global assessmentscores increased from -1.4 to +1.4. Improved QoL wasdemonstrated by increases in the Physical CompositeScore (29.0 to 32.3) and Mental Composite Score (33.3to 38.7) on the SF-36v2 (P < 0.001 for all). Adverseevents were reported by 28% (320/1138) of patients inboth groups, most frequently constipation (12%) andnausea (7%). The tolerability profile was similar in bothgroups.Conclusion: Results indicate that Kadian is as effica-cious and well tolerated for treating neuropathic pain asit is for other pain types.

References

1 Dworkin RH, et al. Advances in neuropathic pain:Diagnosis, mechanisms, and treatment recommenda-tions. Arch Neurol 2003;60:1524–34.

2 Ware JE, et al. How to score version 2 of the SF-36(r)health survey. Lincoln, RI: Quality Metric Incorpo-rated; 2000.

Funding: Alpharma US Pharmaceuticals BrandedProducts Division.March/April 200562MiscellaneousAbstractAbstract

121Clinical

Septic Facet Joint Arthritis after a Corticosteroid Facet Injection

Toby Weingarten, MD, Mayo Clinic Foundation, Rochester, MNW. Michael Hooten, MD, Mayo Clinic, Rochester, MNAnne E. Ptaszynski, MD, Mayo Graduate School of Medicine, Rochester, MNIntroduction: Infections following spinal injections areinfrequently reported complications. We report theoccurrence of a septic facet joint after a lumbar corti-costeroid facet injection.Case Report: A 53-year-old female with recurrent uri-nary tract infections (UTI) was referred for a facetinjection. Sixteen days prior, the patient underwent flu-oroscopically guided bilateral L4-L5 facet injections.On the right, an intra-articular injection was performed(triamcinolone 40 mg). On the left, the intra-articularspace could not be entered and a periarticular injectionwas performed (triamcinolone 50 mg). The patient had3 days of reduced pain but then developed left-sided lowback pain (LBP). She had two medical evaluations and

was referred to our pain clinic for repeat facet injec-tions. Upon presentation, she reported chills, diaphore-sis, and severe left-sided LBP. On examination, she wasafebrile, the left lumbar region was tender, and therewere no neurological deficits. A magnetic resonanceimage (MRI) demonstrated an 8-mm left L2–L3 facetjoint abscess with extension to the left paraspinous mus-culature and epidural space. The patient was hospital-ized and a urine culture grew Escherichia coli. Bloodcultures were negative. The patient underwent a left L2hemilaminectomy, resection of the left L2–L3 facetjoint, and drainage of the abscess. Pathological exami-nation revealed an acute abscess but culture of abscessmaterial remains negative to date. She is receivingbroad spectrum antibiotics and further follow-up isunderway.Discussion: This is the fifth reported infectious compli-cation after a facet injection. The risk factor for thispatient included recurrent UTIs. In the previous cases[1–4], worsening LBP was the presenting symptom.The time from injection to symptom onset ranged from2 to 35 days but the diagnosis was established an averageof 14 days after symptoms developed. Following facetinjections, an infectious complication should remainparamount in the differential diagnosis of worseningback pain.

References

1 Cook NJ, Hanrahan P, Song S. Paraspinal abscessfollowing facet joint injection. Clin Rheumatol1999;18:52–3.

2 Magee M, Kannangara S, Dennien B, et al. Paraspi-nal abscess complicating facet joint injection. ClinNucl Med 2000;25:71–3.

3 Alcock E, Regaard A, Browne J. Facet joint injection:A rare form cause of epidural abscess formation. Pain2003;103:209–10.

4 Orpen NM, Birch NC. Delayed presentation of sep-tic arthritis of a lumbar facet joint after diagnosticfacet joint injection. J Spinal Disord Tech 2003;16:285–7.


122Clinical

Efficacy of Comprehensive Pain Management Approach to Treating Chronic Knee Pain

Mark-Friedrich Hurdle, MD, Mayo Clinic, Rochester, MNThere is minimal research on the characteristics ofpatients with chronic knee pain or on the efficacy ofcomprehensive rehabilitative interventions for treatingthis population. These patients have often failed con-

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ventional therapies including medications, physicaltherapies, corticosteroid injections, and surgical proce-dures. The present study examined 15 patients withchronic knee pain treated at the Mayo Clinic PainRehabilitation Center between 1998 and 2003. Themean patient age was 50 (SD = 17, range 18–76). Thir-teen patients were female and two were male. Theyaveraged 14 years of education (SD = 2.9) and 2.5 yearsof pain (SD = 0.3). All 15 patients completed the entire3-week course. Diagnoses related to the developmentof chronic knee pain include knee arthroplasty, arthritis,trauma, and infections. All patients completed pre- andpost-treatment assessments including the Health StatusQuestionnaire (HSQ), Multidimensional Pain Inven-tory (MPI), Center for Epidemiological Studies-Depression (CES-D), and the Coping StrategiesQuestionnaire (CSQ) [1–3]. Pretreatment question-naire results were significant for major depression in53% (N = 8) of patients with a CES-D ≥ 27. After com-pleting rehabilitation, paired t-tests revealed significantdecreases in pain severity/suffering (P < 0.05), depres-sion (P < 0.05), catastrophizing (P < 0.01), andimproved physical functioning (P < 0.05). This patientpopulation, which has not often been described in themedical literature, has a significant level of depressionand debilitation warranting future research. Further-more, these findings suggest that patients with severe,chronic knee pain can significantly improve physicaland emotional functioning in a pain rehabilitationprogram that incorporates multimodality therapies.

References

1 Radloff LS. The CES-D Scale: A self-report depres-sion scale for research in the general population. ApplPsychol Meas 1977;1(3):385–401.

2 Kerns RD, Turk DC, Rudy TE. The West Haven–Yale Multidimensional Pain Inventory (WHYMPI).Pain 1985;23(4):345–56.

3 Rosenstiel AK, Keefe FJ. The use of coping strategiesin chronic low back pain patients: Relationship topatient characteristics and current adjustment. Pain1983;17(1):33–44.


123Clinical

Interscalene Brachial Plexus Block in a Patient with Adhesive Capsulitis Following Shoulder Hemiarthroplasty: A Case Report

Wendi Lundquist, DO, Loyola University, Maywood, ILRaj Uppal, MD, Hines VA Hospital, Maywood, ILDave Shashank, DO, Loyola University and Hines VA Hospital, Maywood, IL

Setting: Outpatient Veteran’s Administration painclinic.Patient: Fifty-five-year-old right-handed male thatunderwent left shoulder hemiarthroplasty secondary toproximal humeral head fracture.Case Description: This patient presented to the painclinic with persistent left shoulder pain and limitedrange of motion (ROM) following shoulder hemiar-throplasty 6 months prior to visit. At that time patientdeferred surgical intervention and opted to maximizeconservative care. Interscalene brachial plexus block wasperformed on two occasions. Both blockades precededaggressive physical therapy that included glenohumeralmobilizations, prolonged passive stretching, and scapu-lar mobilizations. Increased passive ROM was demon-strated following first blockade in forward flexion (107/70) and abduction (107/70) and this 107 degrees wasmaintained following the second block. Patient didreport more pain with movement after second blockcompared with the first.Assessment/Results: Adhesive capsulitis and pain fol-lowing shoulder hemiarthroplasty are known complica-tions that can result in functional impairment. Previousstudies have demonstrated that patients with adhesivecapsulitis have benefited from interscalene brachialplexus blockade with immediate aggressive physicaltherapy to increase ROM. This is the first report knownto the authors of the use of interscalene brachial plexusblockade prior to physical therapy to increase ROM forpatients that have developed adhesive capsulitis follow-ing shoulder hemiarthroplasty.Discussion: In this patient, significant improvement inROM was reported after blockade. This may be aneffective method to increase ROM in patients withadhesive capsulitis following shoulder hemiarthroplasty.Further studies are indicated to confirm its efficacy inthese patients.

References

1 Lierz P, et al. Interscalene plexus block for mobiliz-ing chronic shoulder stiffness. Wien Klin Wochen-schr 1998;110(21):766–9.

2 Roubal PJ, et al. Glenohumeral gliding manipulationfollowing interscalene brachial plexus block inpatients with adhesive capsulitis. J Orthop SportsPhys Ther 1996;24(2):66–77.


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124Clinical

Hospitalizations, Undesirable Behavior, and Outcomes in Persons on Narcotics

Donna Bloodworth, MD, Baylor College of Medicine, Houston, TXIntroduction: Opioid trials to treat benign chronic painare controversial, but the incidence and correlation ofhospitalizations and abnormal behaviors is not defined.Purpose: This retrospective chart review catalogueshospital contacts and abnormal behaviors during opioidtreatment.Methods and Materials: The charts of 105 adults (63females, 43 males; 57 white, 43 black, 7 Latin; averageage 50.8 years, duration of pain 7.1 years, initial VNS7.38), referred to treat chronic pain at an urban countyhospital between May 2002 and August 2003, werereviewed for specific behaviors.Results: Forty-one patients were followed long term,14 were discharged, 4 died, and 50 did not follow up.Twenty-six patients had 54 emergency room visits (22)or hospitalizations (32: 16 surgeries, 11 medical, and 5psych admissions). Thirteen patients had multipleencounters. Aberrant behaviors included 11 positiveurine tox screens, 8 patients’ obtaining medication fromother sources, and 12 patients’ escalating doses. Twopatients attempted unsuccessful suicide, four patientsdied, and eight MVAs occurred. Only eight (rash, painmeds, anxiety and pain, nausea, withdrawal, belly pain,constipation, and diverticulitis) of 53 hospital encoun-ters are related to narcotics (P = 0.0001, z-test). Elevenof 13 multiple-hospital-visit patients demonstrated oneor more aberrant behaviors, MVA, death or suicidalbehavior; only 4 of 14 single-encounter patients dem-onstrated aberrancy (P = 0.011). The 15 patients whohad aberrant behaviors (11 multiple hospital visits and4 single visits) had 38 hospital encounters, only 6 ofwhich could be related to narcotics (P = 0.0001). Aber-rant behavior also did occur in patients who never wentto the hospital.Conclusions: Chronic pain patients seem to utilize hos-pital resources frequently; however, most hospitalencounters, even in patients with aberrant medicationuse and undesirable outcomes, are related to coexistingmedical, surgical, and psychiatric disease. More severebaseline disease or nontraditional use of healthcareresources is suggested.March/April 200562MiscellaneousAbstractAbstract

125Education

Hospital Pain Improvement Program Changes Pain-Related Myths Held by Hospital Providers

Ike Eriator, MD, MPH, University of Mississippi Medical Center, Jackson, MSShamas Moheyuddin, MD, University of Mississippi Medical Center, Jackson, MSShirley Gibson-MacDonald, RN, BSN, G V Sonny Veterans Administration Medical Center, Jackson, MSIntroduction: Pain management in the hospital settingis a high-volume, high-risk and problem-prone areathat cuts across several areas of patient care, includingpatient rights, assessment, education, provision of care,and staff education. Despite the significant strides madein improving pain control in the past few decades, theundertreatment of pain remains a significant nationaland international problem. Following the implementa-tion of a pain management performance improvementplan how much does the attitude and opinion of nursesand physicians on common pain management mythschange?Materials and Methods: To measure changes in theattitude and practice pattern of the providers, itemswere adapted from previously published studiesaddressing similar issues. Randomly selected chartswere reviewed monthly to monitor progress in docu-mentation. After obtaining baseline data, an interdisci-plinary team was formed and a multiprong approach toimproving hospital-wide pain management was imple-mented. Facets included staff and patient education,screening of pain as fifth vital sign, regular chart review,inclusion of information on pain in new employee ori-entation, training pain resource providers, organizinginformational pain fair, and organizing regular townhall discussions with hospital staffs on pain topics bypain specialist.Results: The questionnaire was administered to about50 randomly selected providers in 1999 and repeatedannually. The results showed that the proportion whobelieved that addiction to pain medication was uncom-mon rose from 50% in 1999 to 68% in 2003. Theappropriate attitude of encouraging patients to talkabout their pain continues to be maintained at a highlevel (76% in 1999 to 89% in 2003).Conclusion: The data suggest that hospital-wide painimprovement programs when carried out using a mul-tidisciplinary, multifaceted approach can lead toimproved pain conceptions among hospital providersand this can be sustained over time.

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References

1 Fife BL, Irick N, Painter J. A comparative study ofthe attitudes of physicians and nurses towards themanagement of cancer pain. J Pain Symptom Manage1993;132:132–9.

2 Levin ML, Berry JI, Leiter J. Management of pain interminally ill patients: Physician report of knowledge,attitudes, and behavior. J Pain Symptom Manage1998;15–40.

3 Dalton JA, Blau W, Lindley C, et al. Changing acutepain management to improve patient outcomes: Aneducational approach. J Pain Symptom Manage1999;17–287.


126Research

Pilot Study of Cervical Disc Decompression for Cervical Radicular Pain Using Coblation Technology

Curtis Slipman, MD, University of Pennsylvania, Philadelphia, PAPhil Tasca, MD, Penn Spine Center, University of Pennsylvania, Philadelphia, PAAmit Bhargava, MD, University of Maryland, Baltimore, MDCynthia Wilson Garvan, MD, University of Florida, Gainsville, FLKinglsey Chin, MD, University of Pennsylvania, Philadelphia, PAMichael dePalma, MD, University of Pennsylvania, Philadelphia, PABackground: The tiered treatment of cervical radicularpain, due to a focal protrusion, which has failed toimprove with noninvasive rehabilitation measures, fre-quently incorporates an epidural/selective nerve rootinjection. Some have investigated the use of percutane-ous discectomy as an additional option to avoid an opensurgical procedure. The reported results of glucocorti-coid injection have been mixed, ranging from 50% to75% success. There are only limited published reportsof percutaneous discectomy. All of them have used lasertechnology, and the methodology of these publicationsobviate the formulation of any judgment concerningtheir success.Purpose: To report the effectiveness and side effectsfollowing percutaneous disc decompression using cob-lation technology combined with a selective nerve rootinjection (SNRI) to treat cervical radiculopathy.Methods: Consecutive patients were prospectivelyenrolled. Inclusion criteria were arm greater than neckpain; corroborative focal protrusion on magnetic reso-nance image (MRI); a minimum of a corroborativemyotomal deficit, positive electrodiagnostic study or

positive diagnostic root block; failure of oral anti-inflammatory medication, physical therapy and/orimminent surgery. Patients were excluded with a focalprotrusion over 5 mm. Side effects were assessed at sixpredetermined postoperative intervals through 2 weeks.Outcomes were assessed using a visual analog scale(VAS) preoperatively and at 2 weeks, 1, 2, 3, and6 months postoperatively. Each subject was reviewed bya spine surgeon to determine if they were a potentialoperable candidate. Data collection was performed byan independent reviewer. Statistical analyses wereaccomplished using McNemar’s and the Wilcoxonsigned rank test.Results: Each of the 21 patients, ranging in age from28 to 54, with an average symptom duration of36 weeks, was considered a potential surgical candidateby a fellowship trained spine surgeon. Mean preopera-tive VAS was 6.9 (range 4–9). Mean serial follow-upinterval VAS rating was: 2.9 (range 0–7.7; 3 with nopain) in 21 patients at 2 weeks; 2.1 (range 0–6.7; 11 withno pain) in 21 patients at 4 weeks; 1.7 (range 0–6.8: 12with no pain) in 21 patients at 8 weeks; 1.2 (range 0–6;8 with no pain) in 21 patients at 3 months; and 1.3(range 0–8; 7 with no pain; 5 with VAS of 1; 3 with VASof 2) in 19 patients at 6 months. There was a statisticallysignificant reduction in the VAS rating at each follow-up (P < 0.0001). As well, there were clinically significantreductions in the VAS rating; mean percentage reduc-tion of 58, 70, 75, 83, and 81 at the respective serialfollow-ups for the entire population (failures and suc-cesses). There were no significant early term sideeffects. One patient underwent successful surgerybetween 8 and 12 weeks post procedure. One patientunderwent repeat disc decompression and snri between3 and 6 months post procedure.Conclusions: This novel approach for the treatment ofcervical radiculopathy merits further scientific investi-gation as 91–95 % (19 or 20 of 21) of patients weresuccessfully treated without any significant side effects.The outcome rate, rapid slope of symptom resolution,stability of response, and high frequency of completearm pain resolution are superior to selective nerve rootblock alone and approximate open surgery.March/April 200562MiscellaneousAbstractAbstract

127Research

Interindividual Differences in Opioid Analgesic Usage in Chronic Pain Patients in Relationship to A118G Mu-Opioid Receptor Polymorphism

Piotr Janicki, MD, PhD, PennState Hershey Medical Center, Hershey, PA

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Vitaly Gordin, MD, Penn State Hershey Medical Center, Hershey, PAGregg Schuler, MSci, Hershey Medical Center, Hershey, PADavid Francis, MSII, Penn State Hershey Medical Center, Hershey, PABackground: Effective analgesic requirements inchronic pain patients during treatment are difficult topredict because these patients show large interindivid-ual variability in nociception and pain response afteradministration of opioid analgesics. Some portion ofthis population are carriers at least one allele for themutated mu-opioid receptor gene (OPRM1). Thismutation (A118G Single Nucleotide Polymorphism orSNP) may be responsible for the expression of analtered mu-opioid receptor (MOR) protein, and pre-sumably altered analgesic response to opioid analgesics,when compared with the carriers of the wild-type MORgene. The objective of this study was to determineallelic frequency and the effect of the A118G SNP ofOPRM1 carrier-status on the interindividual variabilityof nociception and opioid analgesic requirements in thispopulation.Methods: The DNA of 127 chronic pain patientsreceiving long-term treatment with opioid analgesics inthe Pain Clinic of a tertiary, academic medical centerwas analyzed for the A118G SNP. Relationship betweenthe genotype and pain score (measured as numericalrating scale for current, least and worst pain) and opioidanalgesic requirements (expressed in morphine equiva-lents/day) were investigated.Results: A total of 108 patients were homozygous forthe major allele (AA), 18 patients were heterozygous(AG) and 1 patient was homozygous (GG) for the minorallele. This distribution was in Hardy-Weinberg equi-librium. The OPRM1 genotype distribution did notdiffer in subgroups of patients administered opioids bythe oral, systemic (fentanyl patch), or intrathecal routes(chi-square = 1.754, P = 0.723). No significant differ-ences (P > 0.05) in pain scores (5.8 ± 2.2 vs 5.7 ± 1.8)or opioid analgesic requirements (308 ± 773 vs182 ± 160 mg) were found between carriers of majorand minor allele, respectively.Conclusion: No relationship between the OPRM1 SNPpolymorphism and interindividual variability in painscores or opioid analgesic requirements was detected inchronic pain patients.

Reference

1 Yu L. Pharmacogenetics: The OPRM (Mu-Opioid-Receptor) gene. In: Mogil JS, ed. The Genetics ofPain, Vol. 28. Seattle, WA: IASP Press; 2004:239–54.


128Research

Neurological Infarctions Following Cervical Transforaminal Epidural Steroid Injections

Graham Scanlon, School of Medicine, University of California—San Diego, La Jolla, CAShawn Romanowsky, Department of Cell Biology, Scripps Research Institute, La Jolla, CAGery Schulteis, PhD, Department of Anesthesiology, University of California—San Diego, La Jolla, CAMark Wallace, MD, Center for Pain and Palliative Medicine, Department of Anesthesiology, University of California—San Diego, La Jolla, CAIntroduction: Cervical transforaminal injections of cor-ticosteroids/local anesthetics are commonly performedin patients with cervical radiculopathy. One of theinvestigators (M.S.W.) has reviewed a number of med-icolegal cases involving brainstem infarction after thisprocedure. In addition, there are published case reportsof spinal cord infarctions. To better characterize theseserious adverse events (SAEs), all U.S. physician mem-bers of the American Pain Society were surveyed(N = 1,404).Methods: Anonymous surveys were sent asking aboutknown neurological SAEs following a cervical transfo-raminal injection of local anesthetic, corticosteroid, orboth. Additional variables were year of occurrence, set-ting where the procedure was performed, specialty ofthe treating physician, use of fluoroscopy/contrast/localanesthetic/corticosteroid, doses administered, and CT/magnetic resonance image (MRI)/autopsy findings.Undeliverable letters were excluded (N = 64).Results: In all, 286 of 1,340 surveys (21.3%) werereturned. Of these, 61 responses detailed 78 severe neu-rological complications associated with cervical transfo-raminal injections. Outcomes included brainstem/cerebellar/cerebral infarcts (N = 13), spinal cordinfarcts (N = 11), concurrent brain/spinal cord infarcts(N = 2), other neurological sequelae (N = 23), orunspecified (N = 29). Twelve cases resulted in a fataloutcome, six of which were associated with braininfarction. Seventy-seven percent were performed byanesthesiologists and 17% by physiatrists. Medicationsincluded corticosteroid plus local anesthetic (92%), cor-ticosteroid alone (6.2%), and air embolus (1.5%). Allfour cases with steroid alone involved methylpredniso-lone, resulting in cerebellar infarct (N = 3) or posteriorcerebral territory infarct (N = 1). Three of these werefatal outcomes, and two autopsies revealed no vertebralartery trauma.Conclusions: This study demonstrates a significant riskof serious neurological injury after cervical transforam-

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inal epidural steroid injections. The exact mechanism isyet to be determined; however, the results of this studysuggest a strong correlation with the use of methylpred-nisolone. Other possible mechanisms include vertebralartery injury with thrombus formation or an inflamma-tory response to the methylprednisolone at the level ofthe central nervous system end arteries.

References

1 Baker R, Dreyfuss P, Mercer S, Bogduk N. Cervicaltransforaminal injection of corticosteroids into aradicular artery: A possible mechanism for spinalcord injury. Pain 2003;103:211–5.

2 Fitzgibbon DR, Posner KL, Domino KB, et al.Chronic pain management: American Society ofAnesthesiologists Closed Claims Project. Anesthesi-ology 2004;100:98–105.

3 Tiso RL, Cutler T, Catania JA, Whalen K. Adversecentral nervous system sequelae after selective trans-foraminal block: The role of corticosteroids. Spine J2004;4:468–74.

Funding: Department of Family and Preventive Medi-cine, University of California, San Diego.March/April 200562MiscellaneousAbstractAbstract

129Research

Comprehensive Pain Rehabilitation for Men with Fibromyalgia

W. Michael Hooten, MD, Mayo Clinic, Rochester, MNToby Weingarten, MD, Mayo Clinic Foundation, Rochester, MNCynthia Townsend, PhD, Mayo Clinic Pain Rehabilitation Center, Rochester, MNChristopher Sletten, PhD, Mayo Clinic Pain Rehabilitation Center, Rochester, MNBarbara Bruce, PhD, Mayo Clinic Pain Rehabilitation Center, Rochester, MNJeffrey Rome, MD, Mayo Clinic Pain Rehabilitation Center, Rochester, MNIntroduction: The clinical outcomes of comprehensivepain rehabilitation for men with fibromyalgia (FM) havenot been previously reported. This study of men withFM was conducted to test the hypothesis that measuresof depression, pain perception, and psychosocialimpairment are similar to women and that these mea-sures improve during a 3-week outpatient cognitive-behavioral pain rehabilitation program.Methods: This retrospective cohort study included 36consecutive men and 219 consecutive women with FMtreated between January 1998 and May 2004. At bothadmission and dismissal, patients completed the Multi-

dimensional Pain Inventory (MPI) [1], SF-36 HealthStatus Questionnaire (SF-36) [2], Center for Epidemi-ologic Studies-Depression (CES-D) [3], and the Cop-ing Strategies Questionnaire catastrophizing subscale(CSQ-C) [4]. A two-way repeated measures of analysisof variance was conducted to compare men and womenwith FM at the time of admission and dismissal. Addi-tionally, the difference in mean admission and dismissalscores was analyzed using paired t-tests (two-tailed).Results: The mean (SD) age and duration of illness formen was 45 years (12) and 11.8 years (13.5) while themean (SD) age and duration of illness for women was46 years (13) and 9.8 years (9.0), respectively. No statis-tically significant (P > 0.05) gender effect was identified.However, the difference in mean admission and dis-missal scores from six subscales of the MPI and SF-36demonstrated significant improvement (P < 0.001).Similarly, scores from the CES-D and CSQ-C alsoshowed significant improvement (P < 0.001). In gen-eral, pain severity, depression, and catastrophizingdeclined while perceived control, health perception,and physical/social functioning improved.Discussion: These results support the hypothesis thatmen and women with FM have similar measures ofpsychosocial function, health attributes, negative pain-related emotions and depression and that these mea-sures improve markedly following comprehensive painrehabilitation.

References

1 Kerns RD, Turk DC, Rudy TE. The West Haven—Yale Multidimensional Pain Inventory (WHYMPI).Pain 1985;23:345–56.

2 Stewart AL, Hays RD, Ware JE. The MOS short-form general health survey. Med Care 1988;26:724–35.

3 Radloff L. The CES-D Scale: A self-report depres-sion scale for research in the general population. ApplPsychol Meas 1977;1:385–401.

4 Rosenstiel AK, Keefe FJ. The use of coping strategiesin chronic low back pain patients: Relationship topatient characteristics and current adjustment. Pain1983;17:33–44.


130Research

The Influence of Body Weight on Postoperative Acute Pain Management

Corey Scher, MD, Tulane University School of Medicine, New Orleans, LAMariam El-Baghdadi, Tulane University School of Medicine, New Orleans, LA

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Kristen Jones, Tulane University School of Medicine, New Orleans, LAMelvin C. Gitlin, MD, FACPM, Tulane University School of Medicine, New Orleans, LAIntroduction: The ongoing obesity epidemic has cre-ated formidable challenges for physicians engaged inthe postoperative care of these patients. Postoperativepain management of the obese may be challenged byconsiderations of altered airway management, cardiop-ulmonary physiology, drug dosing calculations, andnegative associations by healthcare workers towardthese patients [1]. We compared the satisfaction of post-operative pain management of obese and nonobesepatients.Methods: Twenty patients with a body mass index(BMI) greater than 27 (25% greater than ideal weight)and 20 patients with BMI less than 27 were treated inthe Post-Anesthesia Care Unit (PACU) after jointreplacement surgery utilizing a pain management pro-tocol whereby morphine sulfate was administered basedon body weight and numerical rating scale. Data con-cerning patient satisfaction with pain management,milligrams of morphine administered, and pain scoreswere collected.Results: Seventy-five percent of patients with a BMIless than 27 were satisfied with their pain managementin the PACU, while only 25% of patients with a BMIgreater than 27 were satisfied. Eighty percent ofpatients with BMI greater than 27 received less totalmorphine sulfate, and reported numeric pain scores sig-nificantly higher than patients with BMI less than 27.Conclusion: Obese patients may be at significant riskfor undertreatment of acute postoperative pain. Thismay reflect unwarranted bias against this patient popu-lation [2].

References

1 Teachman BA, Brownell KD. Implicit anti-fat biasamong health care professionals: Is anyone immune?Int J Obes Metab Disord 2001;25(10):1525–31.

2 Wee CC, Phillips RS, et al. Influence of body weighton patient’s satisfaction with ambulatory care. J GenIntern Med 2002;17(2):155–9.


131Research

Duloxetine at Doses of 60 mg QD and 60 mg BID Is Effective in Treatment of Diabetic Neuropathic Pain (DNP)

Joachim Wernicke, PhD, MD, Eli Lilly and Company, Indianapolis, INYili Lu, PhD, Eli Lilly and Company, Indianapolis, IN

Michael Robinson, MD, Eli Lilly and Company, Indianapolis, INDeborah D’Souza, Eli Lilly and Company, Indianapolis, INAmy Waninger, Eli Lilly and Company, Indianapolis, INPierre Tran, Eli Lilly and Company, Indianapolis, INObjective: Serotonin (5-HT) and norepinephrine (NE)are involved in pain modulation via descending inhibi-tory pathways in the brain and spinal cord. This studyassessed the efficacy of duloxetine, a potent, selective,and balanced inhibitor of 5-HT and NE reuptake, onthe reduction of pain severity, in patients with neuro-pathic pain (DNP).Methods: Patients with DNP and without comorbiddepression were randomized to treatment with dulox-etine 60 mg QD, 60 mg BID, or placebo for 12 weeks.The primary outcome measure was the weekly meanscore of 24-hour average pain severity on the 11-pointLikert scale. Secondary measures included night and24-hour worst pain severity, Brief Pain Inventory (BPI),Clinical Global Impression of Severity (CGI-Severity),Patient Global Impression of Improvement (PGI-Improvement), Short-Form McGill Pain Question-naire, Dynamic Allodynia, and Average Daily Intake ofAcetaminophen.Results: Duloxetine 60 mg QD and 60 mg BID dem-onstrated significant improvement in the treatment ofDNP and showed rapid onset of action, with separationfrom placebo occurring at week 1 on the 24-hour aver-age pain severity score. For all secondary measures forpain (except allodynia), mean changes showed superior-ity of duloxetine over placebo, with no significant dif-ference between 60 mg QD and 60 mg BID. Reductionin 24-hour average pain severity was caused by directtreatment effect. CGI and PGI evaluation also demon-strated greater improvement on duloxetine- versusplacebo-treated patients. Duloxetine showed no notableinterference on diabetic control, and both doses weresafely administered and well tolerated.Conclusion: This study confirms previous findings thatduloxetine at 60 mg QD and 60 mg BID is safe andeffective in treating DNP.

References

1 Iyengar S, Detke M, Ahmad LJ, Simmons RMA.Efficacy of the selective serotonin and norepineph-rine reuptake inhibitor, duloxetine, in the formalinmodel of persistent pain. Eur Neuropsychopharma-col 2002;12(suppl 2):S43.

2 Max MB, Lynch SA, Muir J, et al. Effects ofdesipramine, amitriptyline, and fluoxetine on pain indiabetic neuropathy. N Engl J Med 1992;326:1250–6.

Funding: Eli Lilly and Company.March/April 200562MiscellaneousAbstractAbstract

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132Research

Duloxetine for Patients with Diabetic Neuropathic Pain: A Six-Month Open-Label Safety Study

Joel Raskin, Eli Lilly Canada, Scarborough, CAFujun Wang, Eli Lilly and Company, Indianapolis, INMichael Robinson, MD, Eli Lilly and Company, Indianapolis, INJeffrey W. Clemens, PhD, Eli Lilly and Company, Indianapolis, INChad Stroud, Eli Lilly and Company, Indianapolis, INIntroduction: Duloxetine is a balanced and potentreuptake inhibitor of both serotonin (5-HT) and nore-pinephrine (NE). As 5-HT and NE inhibit pain viadescending spinal cord pathways, duloxetine’s dualreuptake inhibition activity may make it an effectiveagent for the treatment of diabetic neuropathic pain.Study Design: In a 28-week, multicenter, open-labelstudy, 449 patients diagnosed with diabetic neuropathicpain (DN) were randomized 3 : 1 to either duloxetine60 mg BID or duloxetine 120 mg QD treatmentgroups. The primary study objective was to assessduloxetine’s tolerability and safety in DN patients. Stan-dard clinical tests, labs, and electrocardiograms wereperformed for all patients. Secondary efficacy measuresincluded the Brief Pain Inventory (BPI) and ClinicalGlobal Impression of Severity (CGI-S) scales.Results: Protocol completion rates were 63.8% and62.6% for the duloxetine 60 mg BID (N = 213) andduloxetine 120 mg QD (N = 72) patient groups, respec-tively. Both treatment groups showed improvementfrom baseline to end point on all subscales of the BPIand the CGI-S (P < 0.005). Adverse events were themost frequent cause of discontinuation for both treat-ment groups. Statistically significant but clinicallyunremarkable changes occurred in some cardiovascularparameters from baseline to end point. In both dulox-etine treatment groups, heart rate increased slightly(P < 0.05) and systolic blood pressure (BP) was unaf-fected while diastolic BP decreased slightly in duloxet-ine 120 mg QD patients (P < 0.05). A sustained (threeconsecutive visits) BP elevation was reported for 18(5.5%) and 6 (5.4%) of patients receiving duloxetine60 mg BID and duloxetine 120 mg QD, respectively.Conclusions: For patients with DN, duloxetine is tol-erable as demonstrated by its high percentage ofpatients completing the study, can be safely adminis-tered, and was efficacious in improving the painfulsymptoms associated with diabetic neuropathy.

References

1 Iyengar S, Detke M, Ahmad LJ, Simmons RMA.Efficacy of the selective serotonin and norepineph-rine reuptake inhibitor, duloxetine, in the formalinmodel of persistent pain. Eur Neuropsychopharma-col 2002;12(suppl 2):S43.

2 Max MB, Lynch SA, Muir J, et al. Effects ofdesipramine, amitriptyline, and fluoxetine on pain indiabetic neuropathy. N Engl J Med 1992;326:1250–6.


133Research

Remoxy®, A Novel Drug Candidate, Deters Oxycodone Abuse in Humans

Nadav Friedmann, PhD, MD, Pain Therapeutics, Inc., South San Francisco, CAAnnelies de Kater, PhD, Pain Therapeutics, Inc., South San Francisco, CAP.G. Butera, Pain Therapeutics, Inc., South San Francisco, CAL.R. Webster, Lifetree Clinical Research, Salt Lake City, UTS. Ratcliffe, St. Bartholomew’s Hospital, London, UKP.A. van Raders, St. Bartholomew’s Hospital, London, UKR.M. Langford, St. Bartholomew’s Hospital, London, UKAim: Abuse and diversion of controlled-release (CR)oxycodone is of great concern to health officials. Abus-ers can easily extract the full dose of oxycodone fromCR preparations, resulting in an immediate, large spikein oxycodone blood levels and a powerful morphine-likehigh. Recreational use of oxycodone can lead to respi-ratory depression, death, or opiate addiction. In theU.S., oxycodone abuse resulted in over 20,000 emer-gency room visits and hundreds of deaths in 2002.Remoxy is a novel oxycodone formulation designed todeter abuse. Remoxy’s gel-cap formulation provides along-acting dose of oxycodone, yet cannot be abused bycrushing, freezing, heating, or dissolving in water, alco-hol, or other common beverages. The pharmacokineticsof Remoxy versus commercially available CR oxyc-odone are compared after swallowing whole and follow-ing abuse by crushing.Methods: Remoxy 10 mg and a commercially availablesustained-release oxycodone 10 mg were first swallowedwhole by healthy male volunteers. In tests designed tomimic common methods of abuse, each drug wascrushed and stirred in water or alcohol before ingestion.After each dosing, plasma oxycodone levels were

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monitored for 48 hours and also compared with thoseproduced by an immediate-release (IR) commercialoxycodone formulation.Results: Remoxy and the commercial CR formulationproduced similar plasma oxycodone levels when eachwas swallowed whole. After crushing and ingesting withwater or alcohol, the commercial CR formulationresulted in even higher oxycodone plasma concentra-tions than those produced by the IR oxycodone tablet.In contrast, oxycodone plasma concentrations aftercrushing Remoxy were markedly lower at early timepoints compared with both the commercial IR andcrushed CR formulations and only slightly above levelsproduced by swallowing Remoxy whole.Conclusions: These results demonstrate Remoxy is asafer alternative to commercially available CR oxyc-odone. The expected benefits of Remoxy includeless illicit use, less oxycodone diversion, and feweroxycodone-related fatalities.

Funding: Pain Therapeutics, Inc.March/April 200562MiscellaneousAbstractAbstract

134Research

Labor Market, Financial, Insurance, and Disability Outcomes among Near Elderly Americans with Depression and Pain: A National Study

Tian Haijun, PhD, RAND, Santa Monica, CARoland Sturm, PhD, RAND, Santa Monica, CARebecca Robinson, MS, Eli Lilly and Company, Indianapolis, INBackground: Symptoms of depression and pain com-monly coexist and contribute to worsening health statusand higher healthcare costs. We analyzed the relation-ship between depression and pain on labor market,financial, insurance, and disability outcomes amongAmericans aged 55–65.Methods: Cross-sectional data from Wave 3 of theHealth and Retirement Survey, a nationally representa-tive sample of individuals aged 55–65 surveyed in 1996were used. Multivariate regression analyses, controllingfor sociodemographics and chronic health conditions,estimated the association between depression and painon economic outcomes. Outcomes included: work andretirement status, household income and wealth,healthcare costs, government health insurance, socialsecurity, health limitations and activities of daily living(ADLs) affecting work. Primary explanatory variablesincluded the presence or absence of depression with orwithout self-reported pain.Results: Individuals with depression and pain versusthose with conditions singly were less likely to work for

pay, had higher total medical expenditures, and weremore likely to report limitations in ADLs and healthlimitations on work (all P < 0.01). Depression with painstrongly predicted work status, retirement, householdincome, total wealth, total medical expenditures, gov-ernment insurance, social security earnings, limitationsin ADLs, and health limitations affecting work (bothP < 0.01).Discussion: Depression with pain was associated withpoor labor market, financial, insurance, and disabilityoutcomes in a nationally representative sample of nearelderly adults. These cross-sectional analyses cannotidentify causal effects of depression with pain. However,individuals with depression plus pain were at increasedodds of receiving government supports and may haveworse access to care because of leaving employmentearly. Depressed individuals with pain may benefit fromtreatment that addresses the duality of these conditions.Further understanding is needed of the medical profes-sional’s ability to diagnosis and treat these patients andthe perceived barriers individuals face in seeking,accessing, and adhering to treatment.

References

1 Bair MJ, Robinson RL, Katon W, Kroenke K.Depression and pain comorbidity. Arch Intern Med2003;163:2433–45.

2 Benjamin S, Morris S, McBeth J, Macfarlane GJ,Silman AJ. The association between chronic wide-spread pain and mental disorder: A population-basedstudy. Arthritis Rheum 2000;43:561–7.


135Research

Effects of Age, Gender, Body Weight, Race, and Renal Function on the Pharmacokinetics (PK) of Hydromorphone HCl Extended Release (HHER) q24h Capsules in Patients with Persistent Pain

Vijay Vashi, PhD, Purdue Pharma L.P., Stamford, CTStephen Harris, MD, Purdue Pharma L.P., Stamford, CTAlessandra Cipriano, BS, Purdue Pharma L.P., Stamford, CTAhmed El-Tahtawy, PhD, Purdue Pharma L.P., Stamford, CTDanlin Wu, PhD, Purdue Pharma L.P., Stamford, CTIntroduction: To compare the pharmacokinetics (PK)of a once-daily hydromorphone HCl extended release(HHER) (Palladone in the U.S., Palladone XL in the

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UK; Hydal Uno Retard in Austria) capsules in patientswith stable moderate-to-severe pain, mainly associatedwith cancer, for differences based on age, gender, bodyweight, race, and renal function.Methods: Patients were administered HHER capsulesto a stable daily dose of 12–84 mg. After their finalHHER dose, patients provided blood samples for PKover 6 hours. A total of 135 patients were evaluated fortheir steady-state dose-normalized PK metrics, totalexposure (AUC), and trough levels (Cmin).Results: For age (young: 32–64 years (N = 89), elderly:65–75 years (N = 31), very elderly: >75 years (N = 15)),AUC and Cmin increased approximately 31% and 22%,for elderly versus young, and approximately 52% and63%, respectively, for the very elderly versus young;there was significant overlap among and variabilitywithin the groups. Comparing gender (64 males vs 71females) resulted in AUC and Cmin values 20–21%higher for females. There was no correlation betweenbody weight and dose-adjusted exposure or dosage ofHHER. There were no apparent differences in PKobserved based on race/ethnicity (white, black, His-panic), although the small percentage, 12.5%, of non-whites precluded statistical comparisons. PK metricsincreased with decreasing renal function-creatinineclearance (Clcr > 80 mL/minute = normal (N = 54),50–80 = mild (N = 61), 30–49 = moderate (N = 15),<30 = severe (N = 5)): 41% in AUC and 33% in Cminfrom normal to mild impairment, with increases up to64% and 78%, respectively, in patients with severeimpairment.Conclusions: Based on these data, dose adjustment ofHHER in patients does not appear to be necessary fordifferences in age, gender, body weight, race, or normalrenal function.

Reference

1 Cipriano A, El-Tahtawy A, Vashi V, Harris S, Wu D.Effects of age, gender, race, and renal function on thepharmacokinetics of hydromorphone hydrochlorideextended-release capsules in patients with persistentpain. J Pain 2004;5(3 suppl):S66. Presented at theAmerican Pain Society Annual Meeting, Vancouver,Canada, May 2004.


136Research

The Relationship and Outcomes of Depression and Painful Complaints: A 23-Year Follow-up

Rebecca Robinson, MS, Eli Lilly and Company, Indianapolis, INR. Cronkite, Stanford University Medical Center, Palo Alto, CA

J. Robson, Stanford University Medical Center, Palo Alto, CAG. Booster, Stanford University Medical Center, Palo Alto, CAD. Roybal, Stanford University Medical Center, Palo Alto, CAE. Ingudomnukul, Stanford University Medical Center, Palo Alto, CAI. Mabel, Stanford University Medical Center, Palo Alto, CAA. Yiu, Stanford University Medical Center, Palo Alto, CAR. Swindle, Eli Lilly and Company, Indianapolis, INR. Moos, Stanford University Medical Center, Palo Alto, CA

Pain commonly occurs with depression and may beassociated with persistence of depression over time.Therefore, we evaluated the association of pain on 23-year outcomes across depression and matched commu-nity control cohorts. Beginning in 1980, 424 patientstreated for major depression (MDD) and 424 controlscompleted mailed surveys. Twenty-three-year wave par-ticipants included 72.9% and 74.6% of surviving base-line patients and controls, respectively. Analysis ofcovariance was conducted across outcomes adjusting forage, gender, education, and medical conditions.

Compared with controls at the 23-year follow-up,the patient cohort experienced increased painful symp-toms (2.99 vs 2.14 as measured by Patient Health Ques-tionnaire-PHQ) and overall disability from pain (30.16v. 18.12—Graded Chronic Pain Scale) after covariateadjustment (both P < 0.001). Compared with controls,patients who experienced pain were more likely to havecurrent MDD as measured by the PHQ (15.9% vs6.3%, P < 0.013). Among participants with pain (con-trolling for sociodemographics and medical conditions),the depressed patient cohort reported more medica-tions used (3.59 vs 1.81, P < 0.001) and days cut downon usual activities (5.38 vs 3.39; P < 0.015). In theabsence of pain, patients differed from controls only onthe number of medications ever used (2.38 vs 0.933,P < 0.001).

This study illustrates how depression and pain mea-sured 23 years after initiating depression treatmentaffects their long-term functional and workplace out-comes relative to a matched community control cohort.Pain was more prevalent 23 years post index in thedepressed patient cohort compared with the communitycontrol cohort. Among individuals with pain, depressedpatients showed poorer functioning and used moremedications than did controls. Among individuals with-out pain, depressed patients differed from controls only

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in that they used more medications. At 23 years afterthe index depression treatment, patients with currentpain have more severe depression than did patientswithout pain.

Reference

1 Cronkite RC, Moos RH, Twohey J, Cohen C,Swindle R Jr. Life circumstances and personalresources as predictors of the ten-year course ofdepression. Am J Community Psychol 1998;26:255–80.


137Research

Automated vs. Manual Spinal Cord Stimulator Adjustment: A Sensitivity Analysis of Lifetime Cost Data from a Randomized, Controlled Trial

Alexander Khalessi, MS, MD, Johns Hopkins University, Baltimore, MDRod Taylor, PhD, University of Birmingham, Birmingham, MDDavid Brigham, Stimsoft, Inc., Columbia, MDRichard North, MD, Johns Hopkins University School of Medicine, Baltimore, MDObjective: This study tested the lifetime cost savingsachieved with automated, computerized adjustmentversus manual adjustment of spinal cord stimulatorparameters, as impacted by usage time/day, inflationrate, discount rate, and years of use, in patients with“totally implanted” power generators with primarycells, which require surgical replacement whendepleted.Methods: We conducted cost sensitivity analyses usinga standard spreadsheet method with a suitably adjustedstandard equation and data from a previously reportedrandomized controlled trial that compared results withthe two methods of stimulator adjustment.Results: When cost is calculated to consider varioushours/day of use, inflation rates, discount rates, andyears of use, spinal cord stimulation (SCS) treatmentremains significantly less expensive when a patient usesthe automated system to adjust the stimulating param-eters, by comparison with the cost of operating thesystem when the parameters are adjusted manually. Thiscost savings is attributable to increased battery life.Conclusion: Computerized, patient-directed parameteradjustment significantly improves the cost-effectivenessof SCS as a therapy for chronic pain. The economicmodel we developed is robust across a representativerange of study parameters, as determined by sensitivityanalyses.

References

1 North RB, Fowler KR, Nigrin DA, Szymanski RE,Piantadosi S. Automated “pain drawing” analysis bycomputer-controlled, patient-interactive neurologi-cal stimulation system. Pain 1992;50:51–8.

2 North RB, Calkins S-K, Campbell DS, et al. Auto-mated, patient-interactive, spinal cord stimulatoradjustment: A randomized controlled trial. Neuro-surgery 2003;52:572–9.

3 North RB, Brigham DD, Khalessi A, et al. Spinalcord stimulator adjustment to maximize implantedbattery longevity: A randomized, controlled trialusing a computerized, patient-interactive program-mer. Neuromodulation 2004;7:13–25.


138Research

A Randomized Double-Blinded Prospective Study Comparing the Efficacy of Continuous Radiofrequency Lesioning to Pulsed Radiofrequency Lesioning in the Treatment of Lumbar Facet Syndrome

David Kim, MD, Henry Ford Hospital, Detroit, MIMorris Brown, MD, Henry Ford Hospital, Detroit, MIMonish Gariwala, MD, Henry Ford Hospital, Detroit, MISteadman Sankey, PhD, Henry Ford Hospital, Detroit, MIHenry Kroll, MD, Henry Ford Hospital, Detroit, MIIntroduction: Lumbar facet joint denervation of themedial branch of the dorsal ramus by continuous radio-frequency lesioning (RF) has been used for over25 years and has been shown to result in significant painrelief and improved function [1]. Pulsed radiofrequency(PRF) is a new technique introduced in an attempt toreduce postprocedure discomfort and neuritis. This isthe first study to compare efficacy between the twotechniques.Methods: Fifty patients were randomized to receiveeither RF or PRF treatment. Inclusion criteria includedback pain without radiation below the knee of at least1-month duration, reproducible pain, no focal neuro-logical deficits, and a negative magnetic resonanceimage (MRI)/CT scan for disc herniation or stenosis.Two separate diagnostic median branch blocks withlocal anesthetic must have resulted in at least a 50%short-term reduction in pain. The RF group receivedcontinuous energy delivered at 80∞C for 75 seconds,while the PRF group had energy delivered at 42∞C witha pulse duration of 20 millisecond at 460.8 kHz andfrequency of 2 Hz for 120 seconds. Visual AnalogueScale Pain Assessment (VAS) and Modified OswestryLow Back Pain and Disability Questionnaire (OWS)

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were administered at baseline and 3 months post treat-ment. Additional questionnaires were completed docu-menting changes in work status, medication usage,confounding treatments, and complications. Compari-sons between groups were assessed using relative per-centage improvement. Comparisons between groupsand within groups were made of the VAS and OSWusing Student’s t-test and paired t-tests.Results: Of the 50 patients studied, 26 completed thefollow-up evaluation; half received RF and half PRF. Inthe RF group, the VAS improved at 3 months by anaverage of 24.7% (SD 50.1), whereas the PRF groupimproved by 10.6% (SD 45.0). The OWS in the RFgroup improved by an average of 18.3% (SD 30.7), andthe PRF group by 4.1% (SD 44.3). There were nosignificant differences in the relative improvementsbetween groups in either the VAS (P = 0.46) or theOWS (P = 0.35). Within the PRF group, comparisonsof the relative change at 3 months for both VAS(P = 0.21) and OSW scores (P = 0.61) were not signifi-cant. However, within the RF group, the VAS (P = 0.02)and OSW scores (P = 0.03) improved significantly at3 months.Discussion: This study suggests that there was no sig-nificant difference in long-term outcome in the treat-ment of lumbar facet syndrome between the RF andPRF groups. However, in patients who received RFthere was significant improvement in both VAS andOSW at 3 months post treatment, findings not seenwith PRF.

Reference

1 J Neurosurg 1975;43:448–51.March/April 200562MiscellaneousAbstractAbstract

139Research

Anesthesiologists Use Different Patient Selection Criteria Than Neurosurgeons to Predict Success of Spinal Cord Stimulation Therapy

Henry Kroll, MD, Henry Ford Hospital, Detroit, MISteadman Sankey, PhD, Henry Ford Hospital, Detroit, MIMorris Brown, MD, Henry Ford Hospital, Detroit, MIIntroduction: Spinal cord stimulation (SCS) therapyhas been shown to be an effective modality to controlpain [1]. In addition to anesthesiologists, specialists inneurosurgery, neurology, orthopedic surgery, and phys-ical medicine and rehabilitation utilize SCS as part ofthe treatment regimen for chronic pain. Failures withthis treatment have been attributed to implant tech-nique, physiologic adaptation, changing disease state,

increased activity level, and hardware or mechanicalfailures. However, patient selection criteria, particularlypsychosocial factors, were recently identified as the pri-mary reason to explain the inability of patients toachieve sustained long-term pain relief with SCS ther-apy [2]. As part of a national survey, we asked physiciansfrom different specialties to identify patient selectioncriteria felt important to predict success with SCStherapy.Methods: A 38-question survey was mailed to 1,000SCS implanters across the United States in April 2003.Physician specialists surveyed represented anesthesiol-ogy, neurosurgery, neurology, orthopedic surgery, andphysical medicine and rehabilitation. Practitioners wereasked to identify important criteria used in the patientselection process for SCS therapy. Areas surveyed were:1) priority of criteria used for patient selection; 2) per-centage of patients who require psychological evalua-tion prior to trial; and 3) elements of a psychologicalevaluation that eliminate a patient as a candidate for atrial. Physician responses were compared by specialty todetermine practice pattern variances. Statistical signifi-cance between specialties regarding categorical andordinal outcomes was assessed using chi-square tests ofassociation or Fishers exact test. Wilcoxon rank-sumtests were used for percentage outcomes.Results: A total of 165 surveys were completed andanalyzed. As 91% of the respondents were anesthesiol-ogists or neurosurgeons, only these two groups wereincluded for comparative analysis. Compared with anes-thesiologists, neurosurgeons considered a clear etiologyof pain to be a very important factor in the selection ofappropriate candidates for SCS therapy (P < 0.05).However, anesthesiologists identified patients with acurrent substance abuse history as very poor candidatesfor success of this therapy more often than neurosur-geons (P < 0.005). Physicians from both specialtiesrequired psychological evaluation of patients prior toSCS trial in 75–100% of cases (P = 0.2). Borderlinepersonality and bipolar disorder were identified byanesthesiologists more commonly as exclusion criteriafor SCS trial (P < 0.05).Conclusions: SCS therapy is an integral part of themanagement of chronic pain states utilized by physi-cians of different specialties. This survey highlightssignificant differences in selection criteria used by anes-thesiologists and neurosurgeons to identify candidateslikely to be successful with this mode of therapy. Thesedata should serve as an impetus for the development ofwell-controlled prospective studies to assess if these dif-ferences in practice patterns affect patient outcomes.Summary: Significant differences exist between anes-thesiologists and neurosurgeons in the selection criteriaused for SCS therapy, including the identification of a

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clear etiology of the painful condition, presence ofactive substance abuse, and diagnoses of borderlinepersonality or bipolar disorder.

References

1 North RB, Kidd DH, Zahurak M, et al. Spinal cordstimulation for chronic, intractable pain: Experienceover two decades. Neurosurgery 1993;32:384–94.

2 Doleys DM. Psychologic evaluation for patientsundergoing neuroaugmentative procedures. Neuro-surg Clin N Am 2003;14:409–17.

Funding: Medtronic Inc.March/April 200562MiscellaneousAbstractAbstract

140Research

Impact of Depression on Functional Status, Health-Related Quality of Life (HRQoL), and Pain Outcomes in Chronic Low Back Pain Patients Treated with Fentanyl Transdermal System

Mark Kosinski, MA, Quality Metric, Lincoln, RISusan Vallow, RPh, MBA, MA, Janssen Pharmaceutica, Inc, Titusville, NJJeffery Schein, PH, MPH, Janssen Pharmaceutica, Inc, Titusville, NJSteven Ascher, PhD, Janssen Medical Affairs, L.L.C., Titusville, NJClare Harte, MS, MBA, Janssen Medical Affairs, L.L.C., Titusville, NJRichard Shikiar, PhD, MEDTAP International, Bethesda, MDLori Frank, PhD, MEDTAP International, Bethesda, MDMary Kay Margolis, MHP, MHA, MEDTAP International, Bethesda, MDGary Vorsanger, MD, PhD, Janssen Medical Affairs, L.L.C., Titusville, NJIntroduction: This study investigates the impact ofcomorbid depression on functional status and pain out-comes in chronic low back pain (CLBP) patients treatedwith transdermal fentanyl.Methods: Data come from an observational study con-ducted at 17 clinical centers in the U.S. eligible patients(N = 131) who had CLBP for >3 months and werereceiving short-acting opioids when transdermal fenta-nyl was added. Patients completed the Treatment Out-comes in Pain Survey (TOPS), the SF-36 HealthSurvey, the Oswestry Disability Index (ODI), and a 10-point numerical rating scale (NRS) of pain severity atbaseline and after >9 weeks of transdermal fentanyltreatment. Comorbid depression was defined as a score

<42 on the SF-36 mental health scale at baseline andfinal visits. Nondepressed patients scored >42 on theSF-36 mental health scale at baseline and final visits.Changes in TOPS, SF-36, ODI and NRS scores frombaseline to final visits were compared betweendepressed and nondepressed CLBP patients usingStudent’s t-tests.Results: Nearly one-half of CLBP patients had comor-bid depression (N = 62). Nondepressed CLBP patientsshowed significantly larger improvement thandepressed CLBP patients in SF-36 physical functioning(5.4 vs 1.6 points, P < 0.01), role physical (5.2 vs 2.1points, P < 0.05), and physical summary (6.3 vs 2.5points, P < 0.05) scales, the TOPS lower body function-ing (11.3 vs -4.9 points, P < 0.05) and total painexperience (-9.8 vs -5.9 points, P < 0.05) scales, theODI (-11.9 vs -3.5 points, P < 0.01), and the NRS(-1.9 vs -1.1 points, P < 0.05). Changes in other SF-36and TOPS scales were generally greater among non-depressed CLBP patients, although the differences werenot statistically significant.Conclusion: Although depressed CLBP patients real-ized HRQoL improvements with transdermal fentanyl,this improvement was generally more favorable in non-depressed patients. Effective management of pain andHRQoL outcomes in CLBP patients requires an assess-ment of comorbid depression.

Funding: Janssen Medical Affairs, L.L.C.March/April 200562MiscellaneousAbstractAbstract

141Research

Analgesic Effects of Preoperative Versus Postoperative Femoral Nerve Block in Patients Undergoing Total Knee Replacement Surgery

Lynn Johnson, MD, MS, Pain Management Center, Pitt County Memorial Hospital, Greenville, NCLayne Johnson, Pitt County Memorial Hospital, Greenville, NCMaura McAuliffe, CRNA, PhD, FAAN, East Carolina University School of Nursing, Greenville, NCLisa Nocera, MD, Pain Management Center, Pitt County Memorial Hospital, Greenville, NCMelanie Furimsky, DO, Pain Management Center, Pitt County Memorial Hospital, Greenville, NCIntroduction: Femoral nerve block (FNB) is commonlyused to alleviate pain after total knee replacement(TKR). Although the efficacy of this block is estab-lished, the effects of preoperative versus postoperativeFNB have not been studied. The aim of this study wasto compare the effects of preoperative versus postoper-ative FNB in patients undergoing TKR.

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Material and Methods: Thirty patients were enrolledin the study. Patients were randomly assigned into twogroups with both groups receiving general anesthesia.Group A received FNB preoperatively and group Breceived FNB postoperatively. FNB consisted of asingle injection technique of 30–40 mL of ropivicaine0.5% with epinephrine. A nerve stimulator was usednerve identification. Pain scores were assessed with avisual analog pain scale (VAS) at hourly intervals in therecovery room (RR), the morning after surgery and atthe completion of the study. Narcotic requirements inthe operating room, RR, and ward were collected foreach patient.Results: Twenty-nine patients completed the study.Group A had 14 patients and group B had 15 patients.The two groups were similar with respect to age andsex (P > 0.05 NS). No differences were observedbetween groups in pain scores collected in the RR(P = 0.71 NS) or the morning after surgery (P = 0.44NS). Group B had lower pain scores at the completionof the study (P = 0.01). Intraoperative and RR narcoticadministration was similar between groups (P = 0.48NS and P = 0.86 NS, respectively). No differences wereobserved between the groups in postoperative narcoticutilization (P = 0.158 NS).Conclusion: The decision to perform FNB preopera-tively or postoperatively is driven by several factors,including time considerations, patient preference, andreimbursement issues. This study found little evidencethat the timing of the procedure conferred any partic-ular benefit to either patient group.

References

1 Hardman JG, Limbird LE, Goodman Gilman A,editors. The pharmacological basis of therapeutics.10th edition. New York, NY: McGraw-Hill MedicalPublishing Division; 2001.

2 Ferrante FM, VandeBoncouer TR, editors. Postop-erative pain management. New York, NY: ChurchillLivingstone; 1993.


142Research

How Useful Is Level of Satisfaction as an Outcome Measure for Pain Management in Cancer Patients?

Ike Eriator, MD, MPH, University of Mississippi Medical Center, Jackson, MSStephen Tafor, MD, University of Mississippi Medical Center, Jackson, MSIntroduction and Study Aim: Multiple epidemiologicsurveys have documented the high prevalence of painin cancer patients. Many cancer patients would consider

suicide if their pain was not well controlled. One ofthe problems inherent in assessing and managing painis the absence of objective outcome measures for pain.The numeric pain scale and patient satisfaction areoften used as pain outcome measures. The aim of thisstudy was to determine if cancer patients who reportless pain on the numeric rating scale have higher satis-faction compared with those with higher pain levels.Materials, Method, and Results: We surveyed 56oncology patients in the outpatient (39) and inpatient(17) settings, using an adaptation of the American PainSociety quality improvement pain questionnaire. Cur-rent pain scores ranged from 0 to 10 with a medianscore of 3. Sixty-three percent had mild pain (0–3).Sixteen percent had moderate pain (4–6), while 21%reported severe pain (7–10). Forty-seven percent of thepatients surveyed reported that they were very satisfiedwith the way the physicians had managed their paincare, 47% were satisfied, while 5% were dissatisfied.Using chi-square analysis, there was no statistically sig-nificant relationship between the average pain score (inthe last 30 days) and level of satisfaction or the degreeof pain relief obtained with treatment and level of sat-isfaction at P = 0.1 or less.Conclusion: Our results suggest that although level ofpatient satisfaction is commonly used as an outcomemeasure of pain care, there was no statistically signifi-cant relationship between the average pain level ordegree of relief obtained from pain treatment anddegree of patient satisfaction. This needs to be con-firmed with larger studies. Clinicians and researchersshould understand that there are several nonpain-related factors that influence the level of satisfaction ofpatients with their pain care.

References

1 American Pain Society Quality of Care Committee.(Consensus statement): Quality improvement guide-lines for the treatment of acute pain and cancer pain.JAMA 1995;274:1874–80.

2 Gallagher RM. Measurement in clinical disorder:From symptom onset to longitudinal outcome. ClinJ Pain 1999;15:75–6.


143Research

Monitoring Compliance with OxyContin Rx in 14,712 Patients Treated in 127 Outpatient Pain Centers

Michael Kell, MD, PhD, MS, ChE, Labyrinth Institute, Smyrna, GAIntroduction: OxyContin® is one of the most utilizedopioid medications for the treatment of severe, chronic

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pain syndromes. As the popularity of this medicationhas increased, so have reports of drug diversion andOxyContin-associated deaths. This study was con-ducted so to provide quantitative information con-cerning compliance with OxyContin prescriptions inchronic pain patients. Data were also collected for othercommon opioids and illegal drugs (not discussed here).Materials and Methods: Random, urine samples werecollected from 14,712 patients prescribed opioids forchronic pain syndromes by the staff of 127 outpatientpain clinics. Urine samples were analyzed by two, quan-titative, commercial Methods: 1) Abbott FPIA; and 2)GCMS using commercial protocols available from UDTesting, Inc., Marco Island, FL. These protocols adjustraw urine drug concentrations so to compensate forurine dilution, urine pH, body weight, and renal func-tion. Data were collected for commonly prescribedopioids (oxycodone/oxymorphone, hydrocodone/hydromorphone, codeine/morphine, 6MAM), benzodi-azepines, and drugs of abuse by a certified, independentlaboratory.Results: Evaluation of the urine demonstrated that, ofurines collected from patients prescribed OxyContinand analyzed by GCMS and FPIA: 1) 20.1% were neg-ative for opioids; 2) 53.6% failed to be within expectedranges for urine concentration-dose curves; and 3)33.5% were within expected ranges for urine concen-tration-dose curves. Also, 13.7% of patients prescribedmedications other than OxyContin or oxycodone IRwere positive for oxycodone by GCMS and FPIA. Oxy-codone dose-urine concentration curves were generatedusing data from compliant patients (normalized tostandard conditions) for both FPIA and GCMS:(*) FPIA = 40.6*(total daily dose)**0.44(*) GCMS = 142*(total daily dose)Conclusion: The quantitative urine opioid, monitoringprotocol commercialized by UD Testing, Inc., usingeither FPIA or GCMS, is a viable tool for monitoringcompliance with OxyContin and other opioids prescrip-tions. Such monitoring has demonstrated that manypatients prescribed OxyContin are not compliant withtheir prescriptions. Compliance can be improved byintervention.

Funding: UD Testing, Inc.March/April 200562MiscellaneousAbstractAbstract

144Research

Effective Titration with Oxymorphone Extended Release in Opioid-Naive Patients with Low Back Pain

Errol Gould, Endo Pharmaceuticals, Inc., Chadds Ford, PA

Gabriela Photivihok, CCRA, Endo Pharmaceuticals, Inc., Chadds Ford, PAHarry Ahdieh, PhD, Endo Pharmaceuticals, Inc., Chadds Ford, PABarbara Nagle, PhD, Endo Pharmaceuticals, Inc., Chadds Ford, PAIntroduction: Opioid-related adverse events (AEs) canlimit tolerability in opioid-naive patients. Cautioustitration from a low dose may improve tolerability. Thisstudy evaluated the tolerability of oxymorphoneextended-release (ER) in opioid-naive patients experi-encing chronic, moderate-to-severe low back pain(LBP) by carefully titrating from a low starting dose(5 mg) to an effective stable dose.Materials and Methods: An open-label study was per-formed in outpatients 18 years of age or older with abaseline pain intensity score of 40 or more on a 100-mm visual analog scale and a pain rating of moderate orsevere on a categorical scale. Patients received oxymor-phone ER 5 mg q12h for 2 days and were then titratedfor 31 days or less to an effective stable daily dose. Theprimary outcome assessment was the tolerability of oxy-morphone ER during dose titration.Results: Forty-eight patients with LBP were enrolled.The mean average pain at baseline was 6.3 on a 0–10scale of increasing pain. Thirty-nine patients (81.3%)were successfully titrated to an effective stable dose thatreduced pain to less than or equal to 4/10 for 3 of 5consecutive days; most stabilized patients (28/39, 72%)were titrated within 14 days. Six (12.5%) patients dis-continued because of AEs and one (2%) each for pro-tocol violation, withdrawing consent, or failure to meettitration criteria. Mean daily dose of oxymorphone ERwas 32.7 mg (range, 10–100 mg). The most commonAEs were those typically associated with opioid treat-ment, including constipation (37.5%), somnolence(25%), and nausea (25%); however, the rate of vomitingwas low (6.3%).Conclusions: Oxymorphone ER was well tolerated bymost opioid-naive patients with chronic, moderate-to-severe LBP when therapy was initiated at a low dose(5 mg q12h), followed by titration to a stable dose thatprovided effective pain relief.

References

1 Petrone D, et al. J Clin Pharm Ther 1999;24:115–23.2 Ruoff G. Pharmacotherapy 1999;19:88–93.

Funding: Endo Pharmaceuticals, Inc., and PenwestPharmaceuticals Co.March/April 200562MiscellaneousAbstractAbstract

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145Research

Duloxetine for the Management of Diabetic Peripheral Neuropathic Pain: Safety and Tolerability in Patients with Baseline Comorbid Conditions

Michael Robinson, MD, Eli Lilly and Company, Indianapolis, INThomas Hardy, MD, Eli Lilly and Company, Indianapolis, INApurva Prakash, Eli Lilly and Company, Indianapolis, INAmy Rosen, MS, Eli Lilly and Company, Indianapolis, INShuyi Shen, Eli Lilly and Company, Indianapolis, INJoachim Wernicke, PhD, MD, Eli Lilly and Company, Indianapolis, INBackground: Duloxetine has been shown to be safe andeffective in the management of diabetic peripheral neu-ropathic pain (DPNP). Diabetic patients are pre-disposed to hypertension and other chronic medicalconditions. Here we assess safety and tolerability datafor duloxetine in patients with DPNP who also hadcomorbid conditions at study entry.Methods: Data were pooled from two double-blind,placebo-controlled studies in which patients(age ≥ 18 years) with a diagnosis of DPNP were ran-domized to receive duloxetine (20 mg QD, 60 mg QD,or 60 mg BID; N = 568), or placebo (N = 223) for 12–13 weeks. Safety assessments included discontinuationrates, spontaneously reported treatment-emergentadverse events, and changes in vital signs.Results: At study entry, mean age across all patients was60.4 years (SD = 10.8), mean duration of diabetes was10.8 years (SD = 9.6), and mean duration of diabeticneuropathy was 3.8 years (SD = 4.1). The most com-monly utilized concomitant medications included anal-gesics (aspirin, acetaminophen), oral antidiabetics(metformin, glibenclamide, glipizide), cholesterol-lowering agents (atorvastatin, simvastatin), and antihy-pertensives (lisinopril, atenolol). The most commoncomorbid conditions among all patients at baseline(other than diabetes mellitus) were hypertension,hyperlipidemia/hypercholesterolemia, gastroesoph-ageal reflux disease, and erectile dysfunction. The rateof discontinuation because of adverse events in dulox-etine-treated patients with baseline hypertensivedisorders was similar to that in patients without hyper-tensive disorders (13.5% vs 14.5%, respectively). Theincidence of treatment-emergent adverse events inpatients with baseline comorbid conditions was similarto that observed in patients who did not have the con-dition at baseline. Mean baseline-to-end point changes

in sitting systolic and diastolic blood pressure (BP) inpatients with baseline elevated BP did not differ signif-icantly from those observed in patients without elevatedBP at baseline (e.g., for sitting systolic BP, elevated:duloxetine -9.3 mm Hg vs placebo -8.4 mm Hg,P = 0.639; normal: duloxetine 3.6 mm Hg vs placebo2.0 mm Hg, P = 0.255).Conclusions: In this study, the safety and tolerability ofduloxetine in the management of DPNP were not sig-nificantly affected by the presence of baseline comorbidconditions

Reference

1 Sowers JR, Epstein M, Frohlich ED. Diabetes,hypertension, and cardiovascular disease: An update.Hypertension 2001;37:1053–9.


146Research

Reduced Addictive Potential of Oxytrex(tm) vs. Oxycodone in Rats

Francesco Leri, PhD, University of Guelph, Guelph, Ontario, CanadaMary C. Olmstead, PhD, Queen’s University, Kingston, Ontario, CanadaLindsay Burns, PhD, Pain Therapeutics, Inc., South San Francisco, CAAim: Oxytrex(tm), a novel drug candidate for moderate-to-severe pain, combines oxycodone and ultra-low-dosenaltrexone, an opioid antagonist. A clinical trial inosteoarthritis showed significantly greater pain relieffrom Oxytrex than from oxycodone. Ultra-low-doseopioid antagonists have also been shown to alleviateopioid tolerance and dependence in rodents. Thepresent work assessed the potential for abuse and addic-tion of Oxytrex versus oxycodone in rat models of drugreward, drug-taking, and drug-seeking.Methods: The acute rewarding or “euphoric” effects ofOxytrex versus oxycodone were assessed in the condi-tioned place preference paradigm. Time spent in anenvironment previously paired with Oxytrex or withoxycodone indicated the rewarding potency of each.Next, the abuse potential of each drug was assessed bymeasuring active drug-taking and subsequent drug-seeking displayed during abstinence. Rats pressed alever for IV infusions of oxycodone or Oxytrex undera schedule of increasing lever-pressing requirements.After three extinction sessions in which drug wasunavailable, lever-pressing was measured again after ratsreceived a “free” injection of oxycodone or were sub-

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mitted to foot-shock stress, mimicking triggers ofrelapse in human addicts.Results: Rats showed a conditioned place preference tooxycodone but not to Oxytrex, suggesting a lack ofrewarding effect of an analgesic dose of Oxytrex. In theself-administration experiment, rats self-administeringOxytrex took more infusions than rats self-administer-ing oxycodone, suggesting a lower rewarding potencyof Oxytrex compared with oxycodone. Rats self-administering Oxytex also showed significantly reduceddrug-seeking precipitated by the triggers of relapse.Conclusion: While providing greater analgesia, Oxytrexmay have a reduced potential for abuse and addictioncompared with oxycodone. The ultra-low-dose naltrex-one component of Oxytrex may suppress the rewardingproperties of oxycodone and the vulnerability torelapse, possibly by reducing opioid-induced neuroad-aptive changes that contribute to addiction.

References

1 Chindalore VL, Butera PG, Yu KP, Burns LH,Friedmann N. Adding ultra-low-dose naltrexone tooxycodone enhances and prolongs analgesia. 2004(submitted).

2 Crain SM, Shen K-F. Ultra-low concentrations ofnaloxone selectively antagonize excitatory effects ofmorphine on sensory neurons, thereby increasing itsantinociceptive potency and attenuating tolerance/dependence during chronic cotreatment. Proc NatlAcad Sci USA 1995;92:10540–4.

3 Wang H-Y, Friedman E, Burns LH. Ultra-low-dosenaloxone suppresses tolerance-associated alterationsin Mu opioid receptor signaling and conformation.Soc Neurosci 2004;Abstract #805.17.

Funding: Pain Therapeutics, Inc.March/April 200562MiscellaneousAbstractAbstract

147Research

Gender Difference in Abuse History Among Black and White Persons with Chronic Pain

Meredith Miller, MD, University of Michigan, Ann Arbor, MITamera Hart-Johnson, MS, University of Michigan, Ann Arbor, MIS. Khady Ndao-Brumblay, PharmD, MS, University of Michigan, Ann Arbor, MIMary Goshon-Blakely, University of Michigan, Ann Arbor, MICarmen R. Green, MD, University of Michigan, Department of Anesthesiology, Ann Arbor, MIPhysical or sexual abuse history is associated withchronic pain (CP); however, most research has focused

only on the prevalence and incidence of abuse inwomen. Gender variations in abuse patterns havereceived little attention. We hypothesized that althoughthe prevalence of abuse is higher in women with CP,men with CP may also suffer from abuse with a differentpattern based on gender and age. A prospective cohortstudy of chronic pain patients 18–50 years at a tertiarycare pain center was conducted. At baseline the Dross-man Abuse Questionnaire (DAQ), the McGill PainQuestionnaire, SF-36, Pain Disability Index, and Post-Traumatic Chronic Pain Test were used. Participantscompleting the DAQ were included in analyses(N = 165; 91% response): women (64%), educated(68% >high school), in a long-term relationship (51%),employed (59%), and Caucasian (50%). Bivariate cor-relations and factor analysis identified six 3-item abusefactors (a = 0.77 - 0.91): sexual molestation (shown sex-ual organs, touched and forced to touch), sexual pene-tration or rape (threat of rape, attempted rape, andactual rape), and physical abuse (threat of hitting orkicking, actual hitting or kicking, and threat of harm)in both childhood and adulthood. The majority ofwomen (50%) and men (61%) reported abuse in child-hood and adulthood (53% and 59%). Women reportedhigher molestation (P = 0.06) and lower physical abusescores (P = 0.01) in childhood than men, and higherpenetration (P = 0.02) in adulthood. In conclusion, ourstudy supports previous findings that men have higherrates of childhood physical abuse. We also found a highprevalence of both rape (18%) and molestation (20%)in childhood among men with CP. These results stressthat questions regarding abuse need to be routinelyasked to both men and women with CP. Furtherresearch is needed to investigate the long-termrepercussions of an abuse history in this understudiedpopulation.

References

1 Green CR, et al. The unequal burden of pain: Con-fronting racial and ethnic disparities in pain. PainMed 2003;4:277–94.

2 Green CR, et al. Do physical and sexual abuse differ-entially affect chronic pain states in women? J PainSymptom Manage 1999;18:420–6.

Funding: AETNA Quality Care Research Fund.March/April 200562MiscellaneousAbstractAbstract

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148Research

Prevalence, Comorbidities, and Utilization of Services of Opioid Abusers in a Managed Care Plan

Vanja Sikirica, PharmD, Janssen Pharmaceutica, Inc., Titusville, NJSusan Vallow, RPh, MBA, MA, Janssen Pharmaceutica, Inc., Titusville, NJJeffery Schein, PH, MPH, Janssen Pharmaceutica, Inc., Titusville, NJDilesh Doshi, PharmD, Janssen Pharmaceutica, Inc., San Diego, CANathaniel Katz, MD, MS, Inflexxion, Inc., Newton, MAAlan White, PhD, Analysis Group, Boston, MAPaul Stang, PhD, Galt Associates, Inc., Blue Bell, PAObjective: To compare the prevalence, comorbidities,and utilization of an “opioid abuse” cohort of managedcare patients with matched controls.Methods: Patients with an opioid abuse diagnosis(ICD-9 codes 304.0¥, 304.7¥, 305.5¥, 965.00, 965.02,965.09) aged 12–64 years were identified in a largemanaged care population July 2000–April 2003. Con-trols without abuse diagnoses were matched 4 : 1 withopioid abusers on age, gender, and zip code. Prevalencerates using annual covered lives as the denominatorwere calculated. Comorbidities and medical service uti-lization were analyzed using descriptive statistics andprevalence ratios (PR) of any utilization. Subset analysisexcluded poisoning diagnoses (965.00, 965.02, 965.09).Results: A total of 1,393 opioid abusers and 5,476 con-trols were identified. Prevalence of opioid abuse was4.7, 5.4, and 6.7 per 10,000 members for 2000, 2001,and 2002, respectively. Opioid abuse was commonly asecondary diagnosis (28.4%). Opioid abusers were seenin outpatient (93.5%) or emergency departments(61.1%). Sixty-three percent of opioid abusers had atleast one claim for an opioid prescription versus 16.3%of controls. Opioid abusers had significantly highercomorbidity prevalence rates of other substance abuse(PR = 21.6), hepatitis B/C (PR = 15.1), cirrhosis/otherliver disease (PR = 11.1), psychiatric diagnoses (PR =8.5), back disorders (PR = 7.7), skin infections(PR = 5.2), arthritis (PR = 4.4), and injury/trauma(PR = 3.2). Annual increases in prevalence, pharmacyutilization differences, and comorbidities persisted insubset analyses.Conclusions: Although prevalence of opioid abuse rosefrom 2000 to 2002, opioid abuse is likely underesti-mated because only diagnosed patients were reviewed.Opioid abusers present with higher prevalence of opioidprescriptions and comorbidities compared with con-trols. To the extent that prescription opioids have a

different abuse potential, payers and providers shouldbalance adequate pain management with these drugs’relative abuse potential. Future research should discernbetween prescription opioid and illicit opioid abusers,while also controlling for comorbidities.

Funding: Janssen Medical Affairs, L.L.C.March/April 200562MiscellaneousAbstractAbstract

149Research

Psychiatric Disorders in Disabled Chronic Low Back Pain Workers’ Compensation Claimants: Utility of the Personality Assessment Inventory

Alex Ambroz, MD, VA Medical Center, Martinsburg, WVChronic low back pain is often associated with psychi-atric problems. It has been estimated that up to 90%of these patients may have psychological problems.Patients will complain of pain because this is moresocially acceptable than having a mental disorder. Thecontinuing pain complaint often results in excessive andunnecessary diagnostic and therapeutic interventions.

In this study we looked at 30 claimants with low backpain who were getting Workers’ Compensation benefitsand had been off work for at least 1 year. We comparedthese with 30 outpatients who had psychological prob-lems and who were being treated with psychotropics. Inorder to assess for possible psychopathology the Per-sonality Assessment Inventory (PAI) was used. The PAIis a self-used objective inventory of adult personalitydesigned to provide information on clinical variables. Itcontains 344 items, which comprise 22 nonoverlappingclinical scales, 4 validity scales, 11 clinical scales, 5 treat-ment scales, and 2 interpersonal scales.

We found that 81% of the Workers’ Compensationclaimants had problems suggestive of major depressivedisorder compared with 46% of outpatients. For som-atization disorder it was 68% compared with 36%. Forborderline personality disorder it was 54% comparedwith 23%. Generalized anxiety disorder was found in45% of claimants and 23% of outpatients. Post-traumatic stress disorder 50% claimants, 20% outpa-tients. Polysubstance abuse was equal in prevalence.Symptoms suggestive of schizophrenia were found in27% of disabled workers and 6% of outpatients.Somatoform pain disorder was in 18% of claimants and6% of outpatients. All of these results were statisticallysignificant. The PAI is suggested as a useful test forevaluation of psychological problems in Workers’ Com-pensation claimants.March/April 200562MiscellaneousAbstractAbstract

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150Research

VAS Score Correlates with Static Surface EMG Signal Intensity in Chronic Spine Pain

Alex Ambroz, MD, VA Medical Center, Martinsburg, WVClara Ambroz, MD, MPH, Disability Evaluation Services, Martinsburg, WVRobert Zucker, MD, MPH, VA Medical Center, Martinsburg, WVEugene Benjamin, MD, VA Medical Center, Martinsburg, WVMarianne Caruso, RN, VA Medical Center, Martinsburg, WVThere is currently no established objective measure-ment for pain intensity. Commonly used methods,including the visual analog scale (VAS), Numerical Rat-ing Scale, Faces Scale, and Brief Pain Inventory, aresubjective pain assessments. The search for an objectivecorrelate for perceived pain intensity is imperative. Arecent meta-analysis of surface-EMG (SEMG) researchpapers found that this procedure can demonstrate cor-relation of pain intensities in patients with low back paincompared with healthy persons, with sensitivities andspecificities between 80% and 90%.

We analyzed 60 noncompensation-seeking patientswho were diagnosed with chronic lumbar or cervicalsprain/strain. VAS scores and static SEMG signals wereobtained before and after a 2-month pain treatmentprogram in a multidisciplinary pain practice. SEMGmeasurements were carried out using a Myovision 8,000unit. Thirty (30) patients reported improvement intheir pain symptoms and were classified as Responders.The mean VAS score on presentation was reported as6, and this corresponded to a mean static SEMG signalamplitude of 542 millivolts. Two months post treat-ment, the reported mean VAS score was 1 in this group,and corresponded to a mean static SEMG signal of 180millivolts. The second group of 30 patients were Non-Responders who did not have pain relief post therapy,with the treatment protocol being identical in the twopatient groups. The mean initial VAS score for theNon-Responders was 6.6 with a mean SEMG signal of884 millivolts. Two months post treatment the meanVAS for Non-Responders was 6.8 with a mean SEMGsignal amplitude of 709 millivolts. We conclude thatstatic SEMG signal intensity can serve as an objectivemeasurement of pain.

References

1 Geisser M, Ranavaya M, Ambroz A, et al. A meta-analytic review of surface electromyography among

persons with low back pain and normal, healthy con-trols. In preparation.

2 Ambroz A, Ambroz C, Zucker R, et al. Surface EMGin chronic paraspinal pain: A review of 44 clinicaltrials. Disabil Med 2003;3(3):87–91.


151Research

Effects of a Structured Opioid Therapy Program, Using Treatment Agreements, Urine Drug Screens, and Consultation, on Primary Care Practice

Nancy Wiedemer, RN, CNP, Philadelphia VA Medical Center, Philadelphia, PAPaul Harden, PharmD, Philadelphia VA Medical Center, Philadelphia, PARobin Arndt, PhD, MD, Philadelphia VA Medical Center, University of Pennsylvania, Philadelphia, PARollin Gallagher, MD, MPH, Philadelphia VA Medical Center, University of Pennsylvania, Philadelphia, PAObjective: Primary care practitioners (PCPs) care formost patients with chronic pain but are reluctant toprescribe opioids, fearing diversion, abuse, addiction,and regulatory scrutiny. Cost-effective strategies areneeded to support PCPs’ pain management. Wedescribe the results of a Nurse Practitioner (NP) andPharm.D intervention, the Opioid Renewal Clinic(ORC), which supported PCP pain management in ahigh addiction risk population within an academicurban tertiary care VA hospital.Methods: The program developed in three stages. 1)Information-gathering and design. Over 6 months,focus groups with PCPs identified needs for an effectiveprogram. 2) Program initiation providing: opioid treat-ment agreements (OTAs), random urine screens(RUDSs) (specific for individual opioids and otherregulated meds), frequent visits, telephone contacts,patient education materials, DEA and state-specificguidelines for opioid prescribing, and consultation. Alldata were recorded electronically in the VA medicalrecord. 3) Maintenance and evaluation. The programwas monitored over 21 months by regular team meet-ings to review patients and protocols. We evaluatedpatient adherence, PCP rates of use of opioid treatmentagreements and urine drug testing, and PCP satisfactionby questionnaire.Results: A total of 335 patients were referred to ORC.Of 170 (50.7%) with documented aberrant behaviors,58 (33%) adhered to the OTA, 54 (32%) self-dis-charged, 22 (13%) were referred for addiction treat-ment, 6 (4%) with consistently negative RUDSs wereweaned from opioids, and 30 (18%) new patients con-tinued monitoring. The 165 (49.3%) referred for com-plexity, including history of substance abuse or need for

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opioid rotation or titration, with no documented aber-rant drug-related behaviors, continued to adhere to theOTAs.Providers: From 2001 to 2003, OTA use increased from63 to 217 per year, RUDSs increased from 420 to 2,536per year. PCPs were highly satisfied.Conclusion: A NP/Pharm.D-run clinic can successfullysupport a primary care practice in managing opioids incomplex chronic pain patients.

References

1 Veterans Health Administration, Geriatrics andExtended Care Strategic Healthcare Group,National Pain Management Coordinating Commit-tee. Pain as the 5th vital sign toolkit. 810 VermontAvenue NW, Washington, DC: 2000.

2 Gallagher RM. Pain medicine and primary care: Acommunity solution to pain as a public health prob-lem. Med Clin North Am 1999;83(5):555–85.

3 Portenoy, RK. Current pharmacotherapy of chronicpain. J Pain Symptom Manage 2000;19:S16–25.


152Research

Comparison of Cyclobenzaprine Alone Versus Cyclobenzaprine plus Ibuprofen in Patients with Acute Musculoskeletal Spasm and Pain

Martin Childers, DO, PhD, University of Missouri—Columbia School of Medicine, Columbia, MOMichelle Petri, MD, DPH, Johns Hopkins Hospital Outpatient Center, Baltimore, MDSteven Gershon, MD, Advanced Pain Management, Virginia Beach, VACharles Laudadio, MD, MBA, McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PADiane Harrison, MD, MPH, McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PAIntroduction: There are few published studies compar-ing the efficacy of a muscle relaxant given alone or incombination with nonsteroidal anti-inflammatory drugs(NSAIDs) for the treatment of acute musculoskeletalspasm and pain. This community-based trial tested thehypothesis that therapeutic outcomes obtained withthe muscle relaxant cyclobenzaprine 5 mg tid (Flexeril5 mg; Cyc5) given alone would be comparable to thoseobtained when this medication was given in combina-tion with ibuprofen (Motrin-IB) 400 mg tid (Cyc5/Ibu400) or ibuprofen 800 mg tid (Cyc5/Ibu800) inpatients with acute musculoskeletal spasm and pain.Methods: Prospective, randomized, open-label, multi-center, 7-day study of Cyc5 versus Cyc5/Ibu400 orCyc5/Ibu800 in patients (males and females, 18–

65 years of age) with acute muscle spasm and pain ofthe back and/or neck of <15 days duration. Spasm andpain were assessed using an 11-point (0–10) patient-rated numerical scale collected via an Interactive VoiceRecognition System after 3 and 7 days of therapy.Results: Significant changes from baseline pain andspasm scores were detected after 3 and 7 days of therapyin all three treatment groups (P < 0.001; Cyc5, N = 288;Cyc5/Ibu400, N = 286; Cyc5/Ibu800, N = 293). Spasmscore changes: Cyc5: -35.2% (D3), -56.0% (D7);Cyc5/Ibu400: -35.5% (D3), -53.7% (D7); Cyc5/Ibu800: -33.3%(D3), -53.8% (D7). Pain score changes:Cyc5: -31.6% (D3), -51.3% (D7); Cyc5/Ibu400:-35.2% (D3), -55.0% (D7); Cyc5/Ibu800: -31.7%(D3), -49.7% (D7). Changes from baseline were signif-icantly greater after 7 days than after 3 days of therapyfor all three treatments (P < 0.001). No significant dif-ferences were detected among the three treatmentgroups. Patients seldom called to spontaneously reportadverse events, regardless of treatment.Conclusions: These results support the hypothesisthat cyclobenzaprine 5 mg tid alone is comparableto cyclobenzaprine 5 mg tid plus ibuprofen (400 or800 mg tid) in the treatment of acute muscle spasm andpain.

References

1 Borenstein DG, Korn S. Efficacy of a low-dose reg-imen of cyclobenzaprine hydrochloride in acute skel-etal muscle spasm: Results of two placebo-controlledtrials. Clin Ther 2003;25(4):1056–73.

2 Toth PP, Urtis J. Commonly used muscle relaxanttherapies for acute low back pain: A review of cariso-prodol, cyclobenzaprine hydrochloride, and metaxa-lone. Clin Ther 2004;26(9):1–13.

Funding: McNeil Consumer & Specialty Pharmaceu-ticals.March/April 200562MiscellaneousAbstractAbstract

154Research

Prevalence and Characteristics of Breakthrough Pain in Noncancer Patients with Chronic Neuropathic Pain

Steven Simon, MD, RPh, Pain Management Institute, Overland Park, KSDaniel Bennett, MD, Integrative Treatment Centers, Westminster, CORichard Rauck, MD, Piedmont Anesthesia & Pain Consultants, Winston-Salem, NCDonald Taylor, MD, Comprehensive Pain Care, Marietta, GASteven Shoemaker, MD, Sagemed, Inc., Boulder, CO

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A survey conducted to evaluate the prevalence and char-acteristics of breakthrough pain (BTP) in patients withchronic noncancer pain identified 48 patients (63%women, 38% men) with primary neuropathic pain diag-noses and controlled baseline pain (T moderate inten-sity). Pain diagnoses included: neuropathy (other) in44%, complex regional pain syndrome in 35%, periph-eral neuropathy in 10%, postherpetic neuralgia in 4%,diabetic neuropathy in 2%, and central pain in 2%. Painhad been present for a median of 6 years (range 1 monthto 55 years). Medications being used included: any opi-oid in 94%, sustained-release opioids in 67%, metha-done in 15%, short acting opioids in 79%, nonsteroidalanti-inflammatory agents in 31%, antidepressants in58%, and anticonvulsants in 56%. Each patient’s painwas characterized by a phone interview using a BTPpain assessment algorithm originally designed for can-cer patients [1]. Seventy-nine percent of these patients(38/48) reported temporary flares of severe or excruci-ating pain (i.e., BTP). Forty-five different types of BTPwere described by 38 patients. The median number ofepisodes per day was 1.5 (range < 1 to 12). Median timeto maximum intensity was 10 minutes (range 0.2 to180 minutes) with 49% of the pains reaching maximumintensity within 5 minutes. Median duration of thepains was 60 minutes (range 5 to 720 minutes). Patientscould identify a precipitant for 60% of the pains and89% of the precipitants were activity related. The onsetof BTP could never be predicted for 49% of the painsand could only sometimes be predicted for 27% of thepains. These results suggest that BTP is common innoncancer patients with chronic neuropathic pain, oftenhas a rapid onset (from baseline to peak intensity), hasa relatively short duration, and is frequently difficult topredict, similar to BTP in cancer patients.

Reference

1 Portenoy RK, Hagen NA. Breakthrough pain:Definition, prevalence and characteristics. Pain1990;41:273–82.

Funding: Cephalon, Inc., and Sagemed, Inc.March/April 200562MiscellaneousAbstractAbstract

155Research

Prevalence and Characteristics of Breakthrough Pain in Noncancer Patients with Chronic Back Pain

Daniel Bennett, MD, Integrative Treatment Centers, Westminster, COSteven Simon, MD, RPh, Pain Management Institute, Overland Park, KS

Richard Rauck, MD, Piedmont Anesthesia & Pain Consultants, Winston-Salem, NCDonald Taylor, MD, Comprehensive Pain Care, Marietta, GASteven Shoemaker, MD, Sagemed, Inc., Boulder, COThe prevalence and characteristics of breakthroughpain (BTP) were assessed in 121 back pain patients(59% women, 41% men) identified in a survey ofchronic noncancer pain patients with controlled base-line pain (< T moderate intensity). Pain had beenpresent for a median of 6 years (range 0.5–40 years).The underlying pain pathophysiology was felt to benociceptive in 55%, neuropathic in 5%, and mixedin 40%. Medications being used included: any opioid in82%, sustained-release opioids in 70%, methadone in18%, short acting opioids in 78%, nonsteroidal anti-inflammatory agents in 28%, antidepressants in 49%,and anticonvulsants in 33%. Phone interviews wereused to characterized each patient’s pain using a BTPpain assessment algorithm originally designed for can-cer patients [1]. Seventy-three percent of these patients(88/121) reported temporary flares of severe or excru-ciating pain (i.e., BTP). Ninety-four different types ofBTP were described by 88 patients. The median num-ber of episodes per day was 2 (range < 1 to 12). Mediantime to maximum intensity was 10 minutes (range 1 to120 minutes) with 48% of the pains reaching maximumintensity within 5 minutes. Median duration of thepains was 50 minutes (range 1 to 480 minutes). Patientscould identify a precipitant for 77% of the pains andmost (96%) of the precipitants were activity related.The onset of BTP could never be predicted for 46% ofthe pains and could only sometimes be predicted for24% of the pains. These results suggest that noncancerpatients with chronic back pain commonly experienceBTP, which often has a rapid onset (from baseline topeak intensity), a relatively short duration, and is fre-quently difficult to predict. These findings are similarto what has been reported for BTP in cancer patients.

Reference

1 Portenoy RK, Hagen NA. Breakthrough pain:Definition, prevalence and characteristics. Pain1990;41:273–82.

Funding: Cephalon, Inc., and Sagemed, Inc.March/April 200562MiscellaneousAbstractAbstract

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156Research

Characterization of Long-Term Intrathecal Ziconotide Use for Patients with Severe Chronic Pain Following Initial Fast Titration

Robert Fisher, MD, R.C. Goodman Institute for Pain Management, Sparks Ambulatory Surgery Center, Fort Smith, ARIvan Lieberburg, MD, Elan Pharmaceuticals, San Diego, CAElizabeth Ludington, PhD, Elan Pharmaceuticals, San Diego, CARobert Howard, BS, Elan Pharmaceuticals, San Diego, CALyle Gee, BS, Elan Pharmaceuticals, San Diego, CAIntroduction: Ziconotide (PRIALT®) is a novel nono-pioid analgesic that is administered intrathecally andtitrated to an effective dose for the management ofsevere chronic pain. To assess whether ziconotide-treated patients would reach stable dose periods duringlong-term therapy, we analyzed patients from two dou-ble-blind placebo-controlled trials with open-labelextensions in severe chronic pain who achieved stabledosing for at least 90 days.Materials and Methods: Characterization included thetime necessary to achieve an initial stable dose, dose ofziconotide during the period of stability, and duration ofstable dosing. Additionally, Visual Analog Scale of PainIntensity (VASPI) scores at baseline, end of titration, andfirst recorded VASPI score during time of dose stabilityare reported. A total of 27 patients received ziconotidefor at least 365 days utilizing initial fast titration. Patientswho achieved a stable dose (constant for >90 days) wereincluded in this characterization (N = 24). The mediantime to stable dosing was 196.5 days (range 4–869 days),the median dose was 0.34 mcg/hour (range 0.09–4.58 mcg/hour) and the median duration of stable dosingwas 131.5 days (range 90–704 days).Results: Clinically significant reductions in meanVASPI scores were observed from baseline (81.1, SD13.3) to end of titration (29.6, SD 26.6) and firstrecorded VASPI during the stable dosing period (49.8,SD 29.9). Safety data for the patients in this character-ization are being analyzed.Conclusion: Fast titration schedules led to substantialimprovements in VASPI scores and a period of stabledosing for the majority of patients who received long-term ziconotide therapy for chronic severe pain. It willbe of interest to determine how the reduction in severepain achieved with ziconotide translates to functionalimprovement.


158Research

Characterization of Long-Term Intrathecal Ziconotide Use for Patients with Severe Chronic Pain Following Initial Slow Titration

Robert Fisher, MD, R.C. Goodman Institute for Pain Management, Sparks Ambulatory Surgery Center, Fort Smith, ARIvan Lieberburg, MD, Elan Pharmaceuticals, San Diego, CAElizabeth Ludington, PhD, Elan Pharmaceuticals, San Diego, CARobert Howard, BS, Elan Pharmaceuticals, San Diego, CALyle Gee, BS, Elan Pharmaceuticals, San Diego, CA

Introduction: The novel nonopioid analgesicziconotide is administered intrathecally and titrated toan effective dose for the management of severe chronicpain. To assess whether ziconotide-treated patientswould reach stable dose periods during long-term ther-apy following an initial slow titration period, we evalu-ated patients with severe chronic pain who receivedziconotide in an open-label safety study.Materials and Methods: Characterization included thetime necessary to achieve an initial stable dose, dose ofziconotide during the period of stability, and durationof stable dosing. Additionally, Visual Analog Scale ofPain Intensity (VASPI) scores at baseline, end of titra-tion, and first recorded VASPI score during time of dosestability are reported. A total of 119 patients receivedziconotide for at least 365 days utilizing initial slowtitration. This characterization included patients(N = 91) who achieved a stable dose of ziconotide (con-stant dose for at least 90 days). All 91 patients whoachieved dose stability had a baseline VASPI score.However, only 89/91 and 49/91 had end of titration anddose stability period VASPI scores, respectively. In thisstudy, VASPI scores were only required at baseline andat the end of titration visits.Results: The median time to dosing stability was279 days (range 4–1,290 days), the median dose was0.24 mcg/hour (range 0.01–2.5 mcg/hour), and themedian length of the dose stability was 141 days (range90–916). Clinically significant reductions in meanVASPI scores were observed from baseline (71.9, SD21.3) to end of titration (49.1, SD 29.0) and during dosestability (59.5, SD 27.9).Conclusion: It was possible to utilize slow titration toachieve substantial reductions in VASPI scores. Also, astable dose for at least 90 days was achieved in a major-ity of patients. Further research is needed to examine

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the relationship between relief of severe chronic painwith ziconotide and functional improvement.

Reference

1 Data on file, Elan Pharmaceuticals: 2004.


159Research

Effectiveness of Intrathecal Ziconotide in Multiple Pain Etiologies: A Meta-Analysis of Three Controlled Trials

Ronald Collins, MD, Tennessee Valley Pain Consultants, Huntsville, ALIvan Lieberburg, MD, Elan Pharmaceuticals, San Diego, CAElizabeth Ludington, PhD, Elan Pharmaceuticals, San Diego, CARobert Howard, BS, Elan Pharmaceuticals, San Diego, CALyle Gee, BS, Elan Pharmaceuticals, San Diego, CAIntroduction: Clinical trials have shown that the non-opioid analgesic ziconotide is useful in managing severechronic pain, including nociceptive and neuropathicpain of malignant, and nonmalignant etiologies.Intrathecal (IT) ziconotide is administered by titratingto an effective dose. Here, Visual Analog Scale of PainIntensity (VASPI) data (0 = no pain to 100 = worst pain)from three double-blind, placebo-controlled trials of457 patients are presented.Materials and Methods: Patients in these studies hadsevere chronic pain that was uncontrolled by multipleoral and IT medications. Pain was classified accordingto whether the pain was malignant or nonmalignant andaccording to pain etiology subgroups. The primary effi-cacy variable, mean percent improvement in VASPIfrom baseline to end of titration, was evaluated for allpain categories; for each pain category two-sided, two-sample t-test was used to evaluate statistical differencesbetween ziconotide and placebo. Analyses were carriedout in each combined subgroup with at least 20 subjects.Results: In patients with nonmalignant pain (N = 402),the mean percent improvement in VASPI score was22.9% in patients treated with ziconotide, comparedwith 7.8% in patients receiving placebo (P < 0.0001). Inpatients with malignant pain (N = 51), the mean percentimprovement in VASPI score was 36.5% in patientstreated with ziconotide, versus 8.6% in the placebo-treated group (P = 0.0230). Significant improvements inthe mean percent improvement in VASPI scores were

observed in patients with myelopathic (19.2% vs 0.1%),neuropathic (29.1% vs 8.9%), radiculopathic (43.7% vs4.1%), and spinal pain (21.3% vs 6.8%). A trend towardimprovement in patients treated with ziconotide com-pared with patients treated with placebo was observedin patients with bone pain. Data from various painetiologies will be presented to explore the effect ofziconotide on VASPI scores.Conclusion: These results indicate that ziconotide iseffective in relieving both malignant and nonmalignantpain of multiple etiologies.

Reference

1 Data on file, Elan Pharmaceuticals: 2004.


160Research

Efficacy of Intrathecal Ziconotide for the Treatment of Severe Chronic Pain in Adults

Lynn Webster, MD, Alpine Pain & Addiction Medicine, Salt Lake City, UTIntroduction: Ziconotide is a nonopioid, N-type cal-cium channel blocker that inhibits neuronal calciuminflux, thereby reducing neurotransmitter release atprimary pain afferents. A double-blind, placebo-controlled, multicenter trial was conducted to assess theanalgesic efficacy and safety of intrathecal (IT)ziconotide in patients with refractory, severe, chronicpain.Materials and Methods: After weaning all IT medica-tions and stabilizing on IT saline for 1 week, patientswith a Visual Analog Scale of Pain Intensity (VASPI)score ≥50 mm were randomized to ziconotide or pla-cebo. The blinded drugs were titrated over a 3-weekperiod, with an initial dosage of 0.1 mcg/hour and a0.35-mcg/hour final target dosage. Primary efficacy wasmeasured by mean percent change of VASPI score frombaseline to the end of titration. Satisfaction with treat-ment and pain relief were assessed with Clinical GlobalImpression (CGI) scales. Adverse events (AEs) wererecorded throughout the study to monitor safety.Results: A total of 112 ziconotide and 108 placebopatients were randomized; 92% of patients completedtreatment. Mean VASPI was 80.7 mm at baseline forboth groups. After 3 weeks, a mean 14.7% VASPI scorereduction for ziconotide patients and 7.2% reductionfor placebo patients was observed (P = 0.036). On theCGI scales, a significantly higher percentage ofziconotide (28.4%) than placebo patients (12.1%)

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reported “a lot” or “complete” satisfaction with treat-ment (P = 0.0027) and “very good” or “excellent” paincontrol (11.9% and 0.9%, respectively; P = 0.0004).The majority (84%) of AEs were mild to moderatein severity; discontinuation because of AEs was 5.4%,ziconotide; 4.6%, placebo. The most frequentlyreported ziconotide-related AEs were dizziness(34.8%), nausea (19.6%), and confusion (14.3%).Conclusions: Ziconotide efficacy was demonstratedin treatment-refractory patients showing significantlyimproved pain levels, patient satisfaction, and overallpain control. Ziconotide was well tolerated with prima-rily mild to moderate AEs and relatively low discontin-uation rates.


161Research

Effective Titration with Oxymorphone Extended Release for Opioid-Naive Patients with Moderate to Severe Pain from Osteoarthritis

Shelly Kafka, MD, Altoona Arthritis and Osteoporosis Center, Duncansville, PAGabriela Photivihok, CCRA, Endo Pharmaceuticals, Inc., Chadds Ford, PAHarry Ahdieh, PhD, Endo Pharmaceuticals, Inc., Chadds Ford, PABarbara Nagle, PhD, Endo Pharmaceuticals, Inc., Chadds Ford, PAIntroduction: Elderly patients using opioids for thefirst time are particularly predisposed to opioid-relatedadverse events (AEs). Opioid-related AEs may be ame-liorated by a low starting dose followed by cautioustitration. We evaluated the safety and tolerability ofoxymorphone extended-release (ER) in opioid-naivepatients experiencing chronic, moderate-to-severeosteoarthritis (OA)-related pain by carefully titratingfrom a low starting dose (5 mg) to an effective stabledose.Materials and Methods: This open-label study was per-formed in outpatients 18 years of age or older with abaseline OA-related pain intensity score of 40 or greateron a 100-mm visual analog scale, and a pain rating ofmoderate or severe. Patients received oxymorphone ER5 mg q12h for 2 days followed by titration over a periodof 31 days or less to a stable dose of oxymorphone ERthat reduced pain to 4 or less on a 0–10 scale of increas-ing pain.Results: Sixty-one treated patients with a mean age(plus or minus standard deviation) of 60 (plus or minus10.9) years had a mean average pain at entry of 6.2/10.

Forty-three patients (70.5%) were successfully titratedto an effective stable daily dose (mean pain 4/10 or less,mean daily dose = 24.4 mg (range, 5–70 mg)). Most sta-bilized patients (56%, 24/43) required 2 weeks or lessof titration. Three patients (4.9%) failed to meet titra-tion criteria, 1 (1.6%) withdrew consent, 1 (1.6%) vio-lated protocol, and 13 (21.3%) discontinued from AEs.AEs were those typical of opioid treatment; the mostcommon AE was constipation (30.0% of patients), andthe rate of vomiting was low (3.3%).Conclusions: The majority of opioid-naive patientswith chronic, moderate-to-severe OA-related pain tol-erate oxymorphone ER well when therapy is initiatedat 5 mg q12h for 2 days, followed by gradual dosetitration.

References

1 Petrone D, et al. J Clin Pharm Ther 1999;24:115–23.2 Ruoff G. Pharmacotherapy 1999;19:88–93.

Funding: Endo Pharmaceuticals, Inc., and PenwestPharmaceuticals Co.March/April 200562MiscellaneousAbstractAbstract

162Research

A Comparison of the Pharmacokinetics of Kadian® and Avinza® 30 mg in Healthy Opioid-Naïve Fed Subjects: A Head-to-Head, Single-Dose Trial

Mike Royal, MD, JD, Private Practice, Ft. Lee, NJIntroduction: KADIAN® and AVINZA® are encapsu-lated pellet formulations of sustained-release morphinesulfate indicated for treatment of moderate-to-severechronic pain. KADIAN, indicated for once-daily orq12h dosing, has no immediate-release (IR) component.AVINZA, indicated for once-daily dosing, has 10% ofits pellets in an IR formulation. This study comparedthe pharmacokinetics of morphine and its mainmetabolites in fed patients receiving KADIAN andAVINZA and the adverse event (AE) profiles of bothformulations.Materials and Methods: An independent CRO per-formed clinical and analytical portions of this ran-domized, double-blind, crossover study. Healthy,opioid-naïve subjects (N = 36) and alternates (N = 4)were randomized to receive either KADIAN orAVINZA 30 mg after a standard meal. Plasma sampleswere obtained hourly for the first 12 hours and at 14,16, 20, 24, 30, 36, 48, and 60 hours. AEs weredocumented.Results: Tmax was significantly earlier for AVINZAthan for KADIAN (6.7 vs 12.9 hours); however,KADIAN provided slightly higher mean plasma mor-

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phine levels than AVINZA at each time point 8–60 hours after a single dose. Cmax and AUC were sim-ilar, and demonstrated bioequivalence based on FDAguidelines [1]. Data on (KADIAN, 14.5 hours;+ 1

2AVINZA, 15.6 hours) demonstrated that both productssupport once-daily dosing. Data on four patients whotook AVINZA were replaced with data from the alter-nates due to vomiting episodes 10–13 hours post dose.AE differences between the products were not statisti-cally significant.Conclusions: The data demonstrated that both+ 1

2products support once-daily dosing. While AVINZAdemonstrated an earlier Tmax, KADIAN providedplasma morphine levels statistically indistinguishablefrom AVINZA throughout most of the 60-hour sam-pling period. Additional clinical trials are needed todetermine whether the formulation differences produceclinically relevant differences when used for long-termtreatment of chronic pain.

Reference

1 Available at: http://www.fda.gov/cder/guidance/3616fnl.htm.

Funding: Alpharma U.S. Pharmaceuticals BrandedProducts Division.March/April 200562MiscellaneousAbstractAbstract

163Research

Lidocaine Patch 5% Improves Sleep, Quality of Life, and Pain Intensity in Geriatric Patients with Neuropathic Pain: A Pooled Analysis

Arnold Gammaitoni, PharmD, Endo Pharmaceuticals, Inc., Chadds Ford, PARoland Onawola, Endo Pharmaceuticals, Inc., Chadds Ford, PABradley Galer, MD, Endo Pharmaceuticals, Inc., Chadds Ford, PA

Persistent, debilitating pain can lead to decreased pro-ductivity, social withdrawal, and depression. Inadequatepain relief can impair a patient’s ability to obtain restfulsleep, as well as adversely affect other quality-of-life(QOL) domains. The objective of this post hoc analysiswas to assess the impact of treatment with the lidocainepatch 5% on pain interference with sleep and otherdomains of QOL in an elderly population of neuro-pathic pain (NP) patients. Data were pooled from threeseparate, open-label, nonrandomized, prospective, 2- to3-week clinical trials. Patients ≥65 years of age whoreported average daily pain intensity >4 (on a 0–10scale) prior to study entry were included in the analysis.Outcome measures included treatment effect at 2 or3 weeks on pain interference with sleep, general activity,mood, walking ability, normal work, relations with oth-ers, enjoyment of life, and on pain intensity as measuredby the Brief Pain Inventory (BPI). In 286 geriatricpatients (mean age, 76.9 years) with NP, 2 to 3 weeks oftreatment with lidocaine patch 5% significantly reducedthe degree to which pain interfered with sleep, and allother domains measured by question 9 of the BPI(P < 0.001). Lidocaine patch 5% also significantlyreduced pain intensity and increased pain relief(P < 0.001). More than half (N = 144, 50.3%) experi-enced a ≥30% decrease in average daily pain from base-line. Treatment-related adverse events (AEs) wereobserved in 49 patients (17.1%), and were primarilymild-to-moderate in severity. The most commonlyreported treatment-related AEs were dermal in nature(i.e., rash, N = 13 [4.5%]). In a geriatric population withNP, lidocaine patch 5% significantly reduced pain inter-ference with sleep and other QOL domains; whileproviding a clinically meaningful reduction in painintensity with low risk of systemic toxicity in an at-riskpopulation.

Funding: Endo Pharmaceuticals, Inc.

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