Fibromyalgia/Chronic Pain Syndrome: An Alternative ...

0896-2960/05/$35.00© 2005 by Begell House, Inc.

Critical Reviews™ in Physical and Rehabilitation Medicine, 17(1):000–000 (2005)

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I. INTRODUCTION

“Complementary and Alternative Medicine” re-fers to treatments that are “generally not used orrecommended within the context of mainstreambiomedical community.”1 Over the last few de-cades, there has been an ever-growing demandfor Complementary and Alternative Medicine(“CAM”). A recent report released by the NationalCenter for Complementary and Alternative Medi-cine (National Institute of Health) found that62% of 31,044 adults interviewed had used someform of CAM therapy in the year 2002.2 A ran-dom telephone survey of 2055 adults by Eisenberget al3 revealed that 42.1% of adults in 1997 hadused CAM during the previous year. This is an

Fibromyalgia/Chronic Pain Syndrome:An Alternative Medicine Perspective

Gordon D. Ko, MD, CCFP(EM), FRCPC,1,2 Scott Whitmore, BSc(PT),2Bob Gottfried, PhD,2 Annie Hum, MD, CAFCI,2 Michael Rahman, ND,3George Traitses, DC,2 Sylvia Loong, BSc(PT),2 Karen Steward, RNCP,2David Berbrayer, MD, MCFP, FRCPC,1 & Michael Jokic, BSc(Hon)11Fibromyalgia Treatment Clinic, Department of Rehabilitation Medicine, Sunnybrook & Women’sCollege Health Sciences Centre, University of Toronto, Toronto, Canada; 2Canadian Centrefor Integrative Medicine, Markham, Ontario, Canada; 3Pinewood Natural Health Centre,Toronto, Canada

* Address all correspondence to Dr. Gordon Ko, 12 Main Street North, Markham, Ontario L3P 1X2; E-mail through thewebmaster at www.musclepainrelief.ca. The authors received no support for this review.

ABSTRACT: Purposes: To review the current literature on pain management in fibromyalgia (FMS) includingcomplementary alternative medicine (CAM) use and to report on treatment and rehabilitation strategies. Methods:A literature review of MEDLINE and EMBASE for published randomized controlled trials for FMS paintreatment was carried out. This was critiqued with the Jadad criteria for quality trials in the chronic pain population.Clinical experience in treating and following such patients over the last 20 years is discussed. Results: Most publishedstudies are of low quality. We report case studies of patients who significantly improved with specific CAMtherapies, indicating the need for future research in these areas. Conclusion: Studies suggest that FMS patients maybe effectively managed for pain with Botulinum toxin A injections with an integrative rehabilitation approach. Thisneeds to be confirmed with large randomized controlled trials.

KEY WORDS: fibromyalgia, chronic pain syndrome, myofascial trigger point, low back pain, migraine, botuli-num toxin A, prolotherapy, neurotherapy, naturopathy, alternative medicine

increase from 33.8% of adults in an earlier 1990study.4 Estimated expenditures for such servicesreveal a 45.2% increase to $21.2 billion in 1997.The total out-of-pocket expenditures for CAM,including costs of herbal therapies, megavitamins,diet products, and CAM literature and equipmentwas conservatively estimated to be $27.0 billion.

In the physiatric-managed population, a sur-vey of 401 working-age individuals with physicaldisabilities revealed that 57.1% used at least oneCAM in the last year.5 A lower percentage of29.1% of rehabilitation outpatients reported suchusage during the last year.6

Another survey of 1035 adults in the UnitedStates noted 40% used CAM and identified pre-dictors of CAM use as being greater education,

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poorer health status, an holistic orientation tohealth, and cultural factors. Dissatisfaction withconventional medicine was not predictive of CAMuse.7 Similar findings were noted in a study of1081 elderly Canadians, with 41.2% (of thosewithout cognitive loss) using CAM.8

From these surveys (Astin, Barnes, Eisenberg),2,3,7

it was concluded that women were more likelythan men to use CAM. When prayer specificallyfor health reasons is excluded from the definitionof CAM, the highest use was noted in the middle-aged (baby boomers). The highest CAM use wasby patients with musculoskeletal problems andarthritis. The highest condition-specific rateswere for neck (57.0%) and back (47.6%) problems.These are conditions commonly seen in physia-tric practice.

One group usually seen with neck and backpain (and, predominantly, middle-aged female)are the fibromyalgia patients.

II. FIBROMYALGIA OVERVIEW

By the American College of Rheumatology (ACR)definition, fibromyalgia is a syndrome of wide-spread muscle pain (over 3 months) and stiffness,with 11 or more characteristic tender points onpalpation.9 It affects 2% of the population, pre-dominantly females, with the most common ageat presentation of 40 to 50 years.10 Symptoms inthe fibromyalgia syndrome (FMS) include (1)musculoskeletal complaints: “hurt all over,” stiff-ness, swollen feeling in tissues; (2) nonmusculo-skeletal: fatigue, poor sleep, paresthesia; and (3)associated syndromes such as irritable bowel (IBS)(41.8% of FMS patients),11 dysmenorrhea,12 fe-male urethral syndrome,13 endometriosis,14 non-cardiac chest pain,15 plantar heel pain,16 migraineheadache (45%),17 temporomandibular joint pain,18

sinusitis,19 and Sjogren’s syndrome.20 A higherincidence of carpal tunnel syndrome (14.1%)21

and Raynaud’s syndrome (38%)22 may explainsome of the paresthesia complaints.

Higher anxiety and depression have also beenreported.23 24 Postulated risk factors for the devel-opment of FMS include a family history of thiscondition,25 a family history of depression and/oralcoholism in first degree relatives,26 childhoodphysical and sexual abuse, eating disorders and

drug abuse,27,28 and hypermobile joint syndrome.29

FMS has also been documented after physicaltrauma30,31 and whiplash,32 but the causal rela-tionship has not been established in a consensusreport on FMS and disability.33 Physical traumaperception is associated with greater disabilitycompensation, and emotional trauma is related togreater functional disability ratings and a highernumber of physician visits.34 A review on psycho-social aspects concluded that the view that FMSis caused by stress or abuse is unproven and thatthere is no evidence that communicating such adiagnosis causes iatrogenic consequences.35

It has been postulated that viral infections mayplay an etiologic role.36 Seventy percent of FMSpatients meet the Centers for Disease Control andPrevention criteria for chronic fatigue syndrome(CFS),37 and 70% of CFS patients meet the ACRcriteria for FMS.38 The usual routine laboratorytests, such as basic hematology, ESR, muscle en-zymes, rheumatoid factor, and ANA, are all nor-mal.39 CFS researchers suggest that deregulation ofthe 2.5A synthetase Rnase L antiviral pathway maybe the pathophysiological reason.40

Muscle biopsy41 and MRI spectroscopy 42 stu-dies have proven to be nondiagnostic. More recentelectron microscopy suggests ultrastructural changesincluding increased DNA fragmentation (possiblydue to persistent focal muscle contractions).43 Sleepstudy findings are abnormal44 but also are notnecessarily specific or unique to FMS.45–47 Re-duced growth hormone secretion48 and elevatedCSF substance P,49 homocysteine,50 and nervegrowth factor levels,51 as well as abnormal neuro-endocrine challenge tests,52–54 suggest a centralpain mechanism, but no reliable diagnostic testhas yet to be established. More recent researchdemonstrates abnormalities on functional MRIimaging studies55–58 and MRI spectroscopy ofparavertebral muscles.59

The economic impact of this syndrome issignificant. Chronic musculoskeletal pain is the #1cause of disability in North America, the #2 causefor visits to the primary care physician and the #3cause for hospitalizations, with over 250,000 spi-nal fusions carried out in the United States. It isestimated that the direct medical cost of FMS tothe U.S. economy is in excess of $16 billionannually.60 The net cost in Canada in 1993 wasestimated to exceed $700 million.61 Despite such

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costs, effective long-term treatment remains elu-sive. The most studied medications to date are thetricyclic derivatives, such as amitriptyline andcyclobenzaprine. Randomized trials (RCT) of theseand other treatments as outlined in Table 1 belowonly show short-term improvement in symptoms.Only the most recent or most comprehensiveRCTs are referenced.

FMS patients are high consumers of non-physician and alternative medical interventions.One study comparing those using such servicesfound no differences in level of pain and functionalimpairment.62 Another study of 111 FMS subjectsfound that 98% had used at least one complemen-tary medical strategy in the preceding 6 months andthat such use was correlated with lower age, higherpain, and higher disability.63 Use of complementarytherapies was seen in patients of a higher socioeco-nomic status and a longer duration of fibromyalgia.The most popular therapy was oral supplementa-tion and the most popular source of advice was frommagazines (40%).64

In September, 2003, Researchers at The Uni-versity of Toronto conducted a survey65 of CAM

in a community education session attended by 72FMS participants and found the following:

Most common products tried:

1. Topical rubs–66.7%2. Sleeping pills–66.7%3. TENS unit–66.7%4. Braces, orthotics–58.3%5. Diets–54.2%6. Over-the-counter oral medications–54.2%7. Glucosamine, herbals, megavitamins–50%

Magnets were tried by 37.5%, and opioids wereused by 41.7%.

Most common CAM therapist/practitioner seen:

1. Massage–75%2. Meditation/relaxation–70.8%3. Acupuncture–70.8%4. Chiropractic–58.3%5. Homeopathy/naturopathy–41.7%6. Spiritual healing/prayer–37.5%

TABLE 1Medications Effective for Pain in FMS

Amitriptyline (10–50 mg effective for first 2 months, but not significant compared to placebo at 6 months).200

Effects may be augmented with the addition of Fluoxetine.201

Cyclobenzaprine (10 mg qhs as effective as 10 mg tid but with less side effects).202

Combined with ibuprofen is helpful for morning stiffness203

Dothiepin (tricyclic similar to amitriptyline).204

Human growth hormone205 (9-month study of 50 FMS females with low IGF-1 levels)Ketamine206 (0.3 mg/kg i.v. drip in prescreened responders)Lignocaine207 i.v. dripMilnacipran (norepinephrine serotonin reuptake inhibitor)208

Odansetron (a 5-Hydroxytryptamine type 3 receptor antagonist)209

Paroxetine210; Venlafaxine (uncontrolled study)210a

SER282 (antidiencephalon immune serum)211

Sodium Oxybate (commercial form of gammahydroxybutyrate)212

Somadril (carisoprodol, paracetamol, caffeine)213

Tizanidine (Zanaflex)214

Topical camphor, methyl salicylate, menthol lotion (uncontrolled study for a duration of 20 minutes)215

Topical capsaicin (35% of neck pain group with FMS )216

Tramadol (i.v. drip, single-dose treatment; 12 patients with 20.6% reduction in VAS pain)217

Tropisetron (5-HT3 receptor antagonist)218

Tryptophan (5 hydroxytryptophan 100 mg tid )219,220

Note: One recent review on pharmacological therapies concluded that the best supported medications to date arethe low-dose tricyclic antidepressants, but that the benefits are short-term and have not been shown to besuperior to placebo at 6 months of study.221,222


The next most used therapies were cranio-sacral therapy, osteopathy, reflexology, hypnosis.These findings were similar to the general popu-lation survey by Eisenberg that rated the 5 mostcommon CAM: relaxation, herbals, massage,chiropractic and spiritual healing.3

Further clinical trials are reported in Tables3A–3D.

In our survey of 116 physiatrists (rehabilita-tion medicine specialists) in Ontario, Canada,55% of respondents agreed that FMS is a “realdisabling condition.” When asked what type ofalternative therapy works, 14 different types werementioned, with the top three being acupuncture,biofeedback, and chiropractic.119

TABLE 2Medications: Published Trials Found To BeNot Effective for FMS Pain

Acetaminophen (paracetamol)74

Calcitonin223

Chlormezanone224

Chlorpromazine225

Imipramine226

Lidocaine (4% injected as sphenopalatinenerve block)227

Lidocaine (i.v. 5 mg/kg), morphine (i.v. 0.3mg/kg)228

Moclobemide229

NSAIDs: Ibuprofen230 (Ibuprofen + alprazolamdid reduce tender-point index (TPI) but notdolorimetry)231

Naproxen 500 mg bid232

Tenoxicam + bromazepan233

Prednisone 15 mg per day (most variablesdeteriorated)234

Ritanserin (a 5-HT2 receptor blocker)235

SSRIs: Citalopram236

Fluoxetine (was helpful for sleep and depression butnot pain at 6 weeks)237

Zolpidem238

Zopiclone239

TABLE 3APhysical Therapies Helpful for FMS Pain

Aerobic exercise66–69 (when combined withflexibility and strength training is superior torelaxation70)

Pool exercise71,72

Hydrotherapy73–75

Low-power laser therapy76,77

Strengthening exercise78,79

TENS (uncontrolled study)80

TABLE 3BPhysical Therapies Not Reported Helpful

Laser81

Shape-of-sleep pillow82

Visible electromagnetic fields83

Note: Exposure to cold tends to aggravate pain inFMS.84,85 One published RCT study found clini-cal effectiveness of ceramic-impregnated gar-ments86 for Raynaud’s (which is experienced by1/3 of FMS patients). A similar study has re-cently been completed for FMS patients.

TABLE 3CPsychological Therapies

Cognitive–behavioral therapy87,88

Group therapy,89 including relaxation and cognitive–behavioral training90

Hypnotherapy91

Meditation-based stress reduction program92

In contrast, a survey104 of FMS patients re-ported different levels of effectiveness. They ratedthe CAM therapy effectiveness on a 5-point Likert-type scale:

–2 markedly worse–1 mildly worse0 no change

+1 mildly better+2 markedly better

Most effective CAM treatment used by atleast 20% of surveyees (avg. score from Likert-typescale ratings):

1. Botulinum toxin A (Botox) injections (1.6)2. Osteopathy/craniosacral therapy (1.4)3. Massage (1.3)4. Spiritual healing/intercessory prayer (1.3)5. Meditation/relaxation (1.2)6. Reflexology, herbals (1.1)

In contrast, medications were rated lower: over-the-counter drugs (0.5), topical rubs (0.7), sleepingpills (0.9), opioids (0.9). Common CAM therapiesrated lower included acupuncture (0.5), chiropractic(0.3), glucosamine (0.25), and magnets (0.1).

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TABLE 3DAlternative Medicine Treatments with Positive Clinical Trials

BiochemicalDHEA supplementation93

Dietary indole supplementation (ascorbigen and broccoli powder)94

Dietary supplementation of coenzyme Q10, combined with Ginkgo biloba extract95

Homeopathy96,97

Multimodality approach, including nutrition and hormone replacement98

SAMe i.v.99 p.o. (improved VAS pain, not TPI, during last week of 6-week study)100

Super Malic (malic acid 200 mg and magnesium 50 mg: 6 tablets bid )101

Topical 024 essential oils101a

Vegan diet102

Electromagnetic (autonomic nervous system)Acupuncture 103–105

Copper wire bedsheet106

Cranial electrotherapy stimulation107

Static electromagnetic fields108

Thermoflow ceramic-impregnated garments108a

PsychoemotionalBiofeedback–relaxation (combined with exercise, best across 2 years)109

Biofeedback–EMG110–113 EEG-driven114

Mind–body therapies115

StructuralChiropractic therapy (4 weeks of spinal manipulation, soft tissue therapy, passive stretching)116

Osteopathy117

Prolotherapy (75% pain improvement; unblinded study)118

TABLE 4Trigger Points and Myofascial PainSyndrome Criteria

Major criteriaPain localized to region, usually unilateral, asymmet-ric tendernessTaut band is palpablePain in known referred zoneExquisite spot tendernessRestricted range of motion due to tight muscle

Minor criteriaReproduction of pain/altered sensation by pressure

on TrPLocal twitch response on snapping the taut bandPain alleviated by stretching muscle or by injecting

TrPDiagnosis requires all the major criteria and at least

one minor criteria.120

One proposed theory for such therapies reliev-ing pain is by resolving muscle “trigger points”(TrP). It is important to distinguish trigger pointsfrom FMS “tender points” (TeP). The criteria forTrP are listed in Table 4.

III. OVERVIEW OF BOTULINUM TOXIN-AFOR PAIN

It has been reported that 72% of FMS patientshave myofascial TrPs.121 Tender points do notusually respond to injections of local anesthetic,but trigger points in FMS do.122 Current theoriesas to the pathophysiology of myofascial TrP in-clude the dysfunctional motor endplate whereexcessive acetylcholine is released.123 Botox is ef-fective for muscle pain/spasticity through its pro-longed blockade of acetylcholine.The active moi-ety, a 150-kDa protein, is the most potent of 7neurotoxins produced by the Gram positive anaero-bic rod-shaped bacteria Clostridium botulinum.124

When injected into muscle, Botox is taken up at

the endplate. Its heavy chain attaches it to thepresynaptic membrane. After endocytosis, thedisulphide bond is broken, allowing the lightchain to move to the presynaptic terminal. There


it binds to 25-kDa synaptosome-associated protein(SNAP-25), which inhibits the calcium-activatedrelease of acetylcholine. The onset of muscle relax-ation occurs around 3 days, with a peak effectaround 3 to 4 weeks and an average duration of 3months. A unit of Botox is defined as the LD50 fora 20-gm Swiss-Webster mouse. (Extrapolated tothe 70-kg human, the lethal dose would be about2700 units). The recommended maximum dose atone treatment is 400 units. Doses are spaced outover 3 months to minimize the risk of developingantibodies that would prevent Botox from working.Reported side effects include flu-like illness (rare),which may last a few days to weeks. Muscle sorenessand stiffness may last 1 to 2 weeks. Inadvertentweakness depends on the injection site/dose (eg,eyelid ptosis, swallowing difficulty) and usually lasts2 to 3 weeks. Endplate targeted injections (withEMG guidance) appear to be more effective thananatomical approaches.125 Botox should be storedin the freezer or refrigerator and reconstituted withpreservative-free normal saline. It loses potency(35%) when stored (in saline) after 1 week and 44%after 2 weeks.126

A. Typical Examples of TreatmentProcedures Using Botox

Patient Profile #1

A 33-year-old married, disabled customer serviceworker had widespread pain and right sciatica for5 years. Chronic pain risk factors included child-hood sexual abuse, major depressive disorder, panicdisorder, agoraphobia; abnormal sleep EEG (rest-less legs, alpha-delta intrusion); slip and fall trauma(Oct., 1988); and car accident (Jan., 1998) (witha 2-week hospitalization), subsequent home care,and wheelchair use.

Previous treatments included physiotherapy,chiropractic, massage, laser, Chan-Gunn acupunc-ture, hydrotherapy, podiatry orthotics, psycho-therapy. Medications included oxycontin, cyclo-benzaprine, relafen, gabapentin, rivotril, stadol,imovane. No response to epidural corticosteroids(CT scan: L5S1 bulging disc, but EMG study wasnormal) or facet joint injections/nerve blocks.

Preinjection findings: (15-03/00) 5′10″ 320 lbs—obese

• 18/18 TeP (3+), with Fischer algometry scoresall <2 kg

• Visual analogue scale (VAS) for pain: 10/10• Fibromyalgia impact questionnaire (FIQ):

69.4/90• Revised Oswestry (OSW): 23/50• Short-form McGill pain questionnaire

(SFMcGill): 37/45

Initial procaine injections were into muscle trig-ger points: trapezii, scalene anticus, right T11erector spinae, right piriformis. Postinjection paindiary recorded short-term improvement.

Botox injections (03-04/00): 200 units spreadout over: R piriformis (3½″ 22-gauge needle), Rerector spinae, both upper trapezii. Injections donewith EMG guidance.

Postinjection (30-05/00): Improved with 5/18TeP (1+ 2–4 kg) VAS: 4/10, FIQ: 11.3/90,OSW: 1/50, SFMcGill: 2/45.

• She reported for the first time in years that shewas able to walk several blocks, make bedswithout help, do laundry, dishes, and mostyard work. She joined weight-watchers.

• (08/00): After 2nd series Botox (400 units),she weaned off oxycontin and NSAIDs com-pletely.

• (11/00): After 3rd series, Botox (400 units),she had lost 34 lbs. and began vocationalretraining.

Further injections were carried out in 04/01(300 units), 10/01 (250 units), 02/02 (200 units).She improved to the point where she could exer-cise regularly, lose weight (down to 258 lbs), andwork part-time. After 2 years, she returned in Feb2004 and had 200 units of Botox administered torecurrent trigger points in the left levator scapulaeand pectoralis minor muscles, right gluteal area.She returned on March 28, 2005, to have moreBotox injections, which she continued to rate asextremely helpful.

Patient Profile #2

A 47-year-old female store owner was diagnosedwith migraines, FMS, and CFS after fumigationgas exposure (1989). Past history: hypothyroidism,

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childhood growing pains, and tailbone fracture.Previous treatments included numerous medicalspecialists. Normal MRI and SPECT scans ofhead. Treated with amitriptyline, NSAIDs, SSRIs,and tryptophan. No headache relief with imitrex,sandomigran, opioids. Tried hydrotherapy, psycho-therapy, and alternative medicines (dental amal-gam removal, intravenous heavy metals chelation,“neural therapy injections”).

Preinjection findings (01/00): 5’8" 145 lbs. BP100/70 mmHg. Wore dark sunglasses.

• Severe (3x/month) left-sided classical migrainesand constant daily tension headaches.

• VAS for headache: 7.5/10; FIQ:70.7/90; 18/18TeP (2-3+).

Botox injections (09/00): Silberstein headacheprotocol (25 units) + upper trapezii (37.5 unitseach).

Postinjection (11/00): Reported (first time in 11years) being completely headache-free for 3 weeks.

• VAS:7/10; FIQ:63.5/90: 18/18 TeP.• (02/01) After 2nd Botox (200 units): VAS: 0/10.

FIQ:53/90.

She subsequently moved out-of-town and waslost to further follow-up.

Patient Profile #3

A 46-year-old married church worker and motherof two, church worker with FMS, IBS, and mi-graines. Taking bellergal, codeine, dicetel andginger, echinacea, milk thistle, garlic, vitaminE,coEnzymeQ10. Risk factors: childhood abuse withalcoholic parents; iv drug abuse (hepatitis C diag-nosed in 1995). Car accident (1989) with whip-lash, right frozen shoulder.

Initial examination (06/00): 5′4″,114 lbs. Noanemia or jaundice. BP134/99 mmHg.

• VAS: 5/10, SFMcGill: 25/45, FIQ: 57/100.• Pain Disability Index (PDI): 30/70. 18/18 4+

TeP (1-1.5kg.)• Treated with hydrotherapy, gabapentin (slowly

up to 2400 mg/day). Weaned off codeine,bellergal.

• (09/00): better appetite and weight: 119 lbs.• VAS: 4/10. SFMcGill: 13/45. PDI: 18/70.

18/18 2+ TeP.

Botox injections (12/00): 25 units for headache+ supraorbital nerve blocks. 75 units: upper trapezii+ splenii cervicis

Postinjection (01/01): Described “an excellentresponse.” Headaches resolved.

• VAS:3/10. SFMcGill:7/45. PDI:11/70.FIQ:14/100. 8/18 TeP.

Returned in March for 300 units and hassubsequently had 8 more Botox injections (en-abling her to continue fulltime work).

Patient Profile #4

A 45-year-old right-handed psychiatrist, whilelost hiking (carrying 5-year-old daughter and 15-lbinfant), developed bilateral arm pain and numb-ness. After 1.5 years of unsuccessful physiotherapy,craniosacral osteopathy, acupuncture, NSAIDs,and cortisone injections, he was referred with“medial epicondylitis, thoracic outlet syndrome(TOS), FMS.” Past health included migraine,anxiety, IBS. Family history included alcoholism,thyroid disease, lung cancer and polio (2 siblings).

Initial examination (12/99): 5′10″, 155 lbs.

• BP 110/70 mmHg (both arms).• Tender epicondyles with positive Cozen’s sign.

1-2+ 12/18 TeP. Normal motor, sensory, re-flex testing. Positive left brachial plexus ten-sion, adson’s and allen’s tests (using portabledoppler). No subclavian bruit.

• Jamar grip strength—left: 75 lbs, right: 95 lbs.• VAS pain: 4/10. PDI: 25/70 with limitations

in writing, recreation, gardening.• Normal investigations included (1) nerve con-

ductions of median, ulnar (including F-wave),medial antebrachial cutaneous motor/sensorynerves, and needle EMG of left arm myo-tomes; (2) bloodwork; (3) ultrasound of elbows.(4) MRI C-spine (minimal disc bulge C5-6).

Arm doppler photoplethysmography confirmedvasculogenic TOS: severely decreased amplitudes


bilaterally with 180° hyperabduction and mode-rate with left costoclavicular and Adson’s tests. Nothrombus noted on color duplex imaging.

• Subsequent therapy (spray-and-stretch, EMGbiofeedback, home exercises) alleviated rightarm pain.

• A persistent left scalene medius TrP was theninjected with 1% procaine. His pain diaryrecorded VAS 4/10 down to 1/10 for a fewhours. Pain was back to 4/10 by the morning.(Figs. 1 and 2)

FIGURE 1. Case study #4. Peripheral Doppler studies demonstrated Thoracic outlet compression on the left,implicating scalene/pectoral tightness.

Further injections, combined with therapy,provided 1 to 2 weeks relief only.

EMG guided injection with 35 units of Botox(15-11/00) was done next, followed by electro-muscular stimulation (Childers’ protocol).

One month post-Botox: VAS: 1/10. PDI: 5/70.Left grip: 100 lbs. 1+ 5/18 TeP.

At 3 months, he described his left arm asbeing 90% improved with Botox. A secondinjection (24-03/01) with 50 units Botox re-sulted in 95% improvement. A year later, hereturned for trigger point lidocaine injections

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FIGURE 2. Pain diary reveals good short-term physiological response to lidocaine injection and predicted positiveresponse to Botox.


into the trapezii. He returned on 23-04/04 forconsultation on a right rotator cuff tendonitisand reported no ongoing TOS symptoms withdaily stretching.

Patient Profile #5

46-year-old single mother of one and registerednurse had a pituitary brain tumor excised in 1988.She was placed on hormone replacement thera-pies, gained 176 lbs in one year and developedwidespread tenderpoints. She underwent her firstBotox treatment in January, 2002, and her sev-enth in April, 2004. She reported that with Botoxshe can work full-time, walk upstairs, sleep better,and is more able to garden and do housework. Shenoted less fatigue, irritability (with her teenageson), depression, and social withdrawal (Fig. 3 andstatistics below [Table 6]).

Patient Profile #6

A 53-year-old woman had post-traumatic head/upper facial pain after a car accident in 1989. CT/

MRI scans were normal. Over the subsequent 10years, she had 12 surgical procedures, including openC2 ganglionectomy, cervical facet rhizolyses—3 times,C2 neurotomy (dorsal ramus medial branch), righttemporal artery excision, bilateral supraorbital nerveresections, and percutaneous microballoon compres-sion of the gasserian ganglion.

Despite palliative nerve blocks from the refer-ring anesthesiologist, she still complained of dailybifrontal headaches radiating to the upper shoul-ders and dorsal neck. Topamax was added tomedications which included Paxil, Oxycontin,Stemetil, Amitriptyline, Ibuprofen, Losec.

Physical examination revealed hypoesthesiain the forehead and C2 distribution. Tendernesswas most noted on the upper trapezii, frontalis andparacervical muscles. She had 18/18 tender pointsand fit the ACR criteria for FMS.

Botox injections administered to the peri-cranial (frontalis, corrugator, procerus, temporalis)and trapezii muscles showed good response, sup-ported by outcome measures and surface EMGrecordings (see Table 5).

Her FIQ score before Botox was 51.4/90.One month after her 10th injection set (Jan.,2004), the FIQ was down to 14.8/90. With

FIGURE 3. Case study #5. Botox injection for low back pain.

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TABLE 5One month

Outcome measure Preinjection post-3rd injection

Visual analogue scale pain 7/10 4/10Headache Disability Index 92/100 84/100Headache Impact Test 68/78 58/78Vernon-Mior Questionnaire 33/50 28/50

Surface EMG RMS Left Right Left Right amplitudes (uV):

FrontalisSitting at rest 2.24 3.99 1.44 0.96Cervical lateral flex 6.97 4.54 1.51 0.98Cervical rotation 6.84 6.73 1.90 1.34

TrapeziusStanding at rest 15.07 5.47 5.20 2.24Cervical rotation 5.36 4.12 2.44 3.10

FIGURE 4. Case study #6. Botox injection for headache or neck pain.

Botox, she reported that she can go shopping andcarry 10 lbs (milk, potatoes), do laundry, dishwash,and stand one hour to cook. Her husband ob-served that she can do ironing without complain-ing of pain. Further injections have been carriedout every 3 months for 11 sessions to date with-out any significant complications. She estimatesit alleviates pain by 75% and is able to reduce herOxycontin (Fig. 4).

Table 6 is a case series of recent fibromyalgiapatients who had repeat Botox injections. Prior tothese injections, all patients had gone throughextensive courses of traditional medications andphysiotherapy and had tried numerous CAMtherapies. Those with failed surgery syndromes(for pain) are marked “�”, and those with painafter motor vehicle accidents are marked “mva.”Further information on these patients is posted at


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http://www.musclepainrelief.ca/ and is the subjectof a forthcoming paper.

B. Discussion of Botox Treatment

One previously published study on Botox forFMS found it not to be effective.127 This was asmall study of 10 patients who underwent alter-nate injections of lidocaine or Botox only intothe upper trapezii. Only one patient reportedrelief of pain for 2 weeks, and that was withlidocaine. On the other hand, several earlierstudies have demonstrated clinical effectivenessfor myofascial pain,128–131 including more re-cently published, randomized double-blindedplacebo-controlled trials (RCT).132,133

Injections into the trapezius may exacerbatepain in FMS patients, particularly in the presenceof a head-forward posture with depressed scapulaeand thoracic outlet syndrome symptoms (painfulparesthesias in the arms and hands). Weakeningthis scapula elevator will aggravate the tension onthe brachial plexus. Instead, injections into thetight pectorals and levator scapulae muscles, com-bined with scapular stabilization exercises(strengthening the trapezius, rhomboids), resultsin a much better clinical response.

Botox has also been demonstrated to be effec-tive in treating headaches (migraine, tension, andcervicogenic types),134–137 FMS patients who alsosuffer from migraine,138 and low back pain.139 Apublished RCT found paraspinal injections of Botoxto be effective for chronic mechanical low backpain.140 Laboratory research provides an explana-tion for Botox in pain control. This includes inhi-bition of calcium mediated release of Substance Pin dorsal root ganglion neurons,141 as well as in thebrain and trigeminal nerve endings.142,143 Botoxalso inhibits other pain neurotransmitters, such asvasoactive intestinal polypeptide144 and calcitoningene-related peptide,145 and by elevation of enke-phalins at the dorsal horn of the spinal cord.146 Ina rat formalin model, Botox was found to havedose-dependent anti-inflammatory effects,147 withthe mediator likely to be glutamate.148,149

Fos expression in the dorsal horn was alsoinhibited.150 On the basis of this finding, we havefound that effectiveness in neuropathic pain con-trol with intradermal injections of Botox is to be

expected.151 152 Clinical experience also suggeststhat the duration of pain relief outlasts the muscle-relaxation effect.153 The literature validates theclinical effectiveness for Botox in appropriatelyprescreened patients.

IV. TYPICAL APPROACHES TO THEFIBROMYALGIA/CHRONIC PAIN PATIENT

A. Thorough Internal Medicine Work-up

It is necessary to rule out other similar and/orconcomitant disorders (hypothyroidism, polymyalgiarheumatica,154 lupus,155 multiple sclerosis, polio,156

cancer, etc.). Prolonged morning stiffness and lim-ited lumbar spine motion in more than one planeis more indicative of other rheumatologic diag-noses.157 A workup should include a detailed neu-rological exam to assess for signs of upper motorneuron dysfunction (hyperreflexia, babinski sign,clonus, abnormal coordination, and gait).158,159

Case A (Fig. 5)

One 38-year-old male patient previously treatedwith numerous therapies, including cortisone injec-tions and paravertebral nerve blocks, was found tohave marked denervation in the thoracic paraspinalmuscles on needle EMG. Subsequent MRI scanrevealed an intradural extramedullary schwanomawith compression of the spinal cord. Surgical exci-sion resolved all his “FMS” symptoms (see patientpointing to surgical scar in Fig. 5).

Other successful neurosurgical cases (with reso-lution of “FMS symptoms”) include those for anintracranial ophthalmic artery aneurysm, colloidcyst, and pituitary adenoma. A comprehensivemedical work-up should always be done to rule outmore serious diseases.160

B. Patients Should Have AlreadyCompleted a Full Trial of MoreConservative Treatments

Conservative treatments include amitriptyline,cyclobenzaprine, NSAIDs, physiotherapy (osteopa-thy, aerobic exercise, aquatherapy), and psycho-therapy (cognitive–behavioural). In our menopausal


patients, hormone replacement therapy may re-solve symptoms all together.161 Some patients alsoexhibit autonomic dysfunction162 and may respondto biofeedback retraining.

C. Patients Should Be Followed andSupported If They Elect to TryAlternative Therapies

Our approach (following Dr. Dietrich Klinghardt’sparadigm) categorizes CAM into four areas:

Neurological

Structural Biochemical

Psychoemotional

1. Structural CAM

Researchers have found success with structuralCAM therapies such as prolotherapy. This in-volves injections into the bone–ligament interface(which stimulate further fibroblast activity), colla-gen deposition, and ligament healing. A recentRCT demonstrated significant improvement inboth the saline and the dextrose injection groups.163

This has led to the recommendation by NikolaiBogduk that such injections be considered in thefirst-line management of chronic low back pain.164

Case B

A 45-year-old, married computer worker (see Fig. 6)with diffuse pain worse in the low back was seenin November, 2000. Clinical exam revealed oldpolio (atrophic small flail right arm and shorter,thinner left leg), 18/18 TePs and marked tender-ness in the left sacroiliac (SI) region. 2+ laxity wasnoted with the shear test for SI instability. Nerve

FIGURE 5. Case example A.


root tension tests were negative, and EMG re-vealed only chronic neurogenic changes. Bloodworkand bone scan were negative for active sacroilitis.

and lidocaine were administered to the SI liga-ments on a monthly basis.

The patient returned 2 years later for a tenniselbow complaint and was pleased to report contin-ued back pain relief.

2. Psychoemotional CAM

Neurotherapy uses an EEG recording system, alongwith training software, to enhance brain waveactivity that is instrumental for improving concen-tration. Much of the research has been focused onchildren with attention deficit disorders.165

Case C

A 48-year-old, married dog breeder (see Fig. 7)developed FMS, with chronic pain, cognitive dif-ficulties, severe depression, and generalized anxi-ety, after an MVA in 1999. After numeroustherapies and medications, she was told that shehad reached maximum recovery. She started neuro-therapy/biofeedback (20 sessions from March toSept., 2003).

After 10 sessions, she estimated 75% improve-ment. She noted that “I can laugh. I am awakeagain and feel as if I am reborn.” After 20 sessions,she was 95% improved and noted that whateverwas left in terms of her concentration deficits wasjust what “people normally face at this age of life.”She could socialize more and engage in variousactivities with her son and husband.

Outcome measures Pre-Rx Post-Rx

VAS pain 7/10 2/10Beck anxiety score 11/63 2/63Beck depression 26/63 8/63Perceived deficits scale 69/80 22/80Fatigue severity scale 42/63 13/63Fibromyalgia Impact 65/90 19/90

Questionnaire

3. Biochemical CAM

Improvements have been reported in some patientsthrough nutritional/ naturopathic interventions.Those with irritable bowel syndrome can be helped

FIGURE 6. Fibromyalgia polio patient improved withprolotherapy.

Pre-Rx Post-6th Rx (06/01)

VAS pain 8/10 4/10Short-form McGill Q. 24/45 19/45Pain Disability Index 44/70 24/70Oswestry LBP score 37/50 15/50Algometry FMS 2.13 kg 3.0 kg

average pain

After trials of physiotherapy, chiropractic, andorthotics (for leg-length correction), prolotherapyinjections with P2G (phenol-glycerine-glucose)


with elimination diets. A young patient was 90%improved by eliminating tartrazine (in red dyes tocolor meats) from her diet. Recent reports alsosuggest a link between FMS and type 2diabetes,166,166a, 166b thus supporting the recom-mendation of a hypoglycemic diet (ie, low intake ofprocessed, refined carbohydrates and sugar). Defi-ciencies have been shown in omega 3 fatty acids167

and in vitamin D.168,168a There are also reports ofheavy metal toxicity, treatment with amalgamremoval and neural therapy.169,170 There is a reportof a dozen patients who have done extremely wellwith the Dr. St. Amand’s protocol. (Paul St.Amand is an endocrinologist and assistant clinicalprofessor of medicine at UCLA).171 This requiresoral guaifenesin that is titrated to promote renalexcretion of inorganic phosphate. Strict dietarychanges, including avoidance of salicylates (in-cluding most brands of toothpaste), is required forthis to work. However, a good randomized con-trolled trial has yet to be done.172

Case D

A 54-year-old, married, retired, left-handed IBMconsultant had FMS for 15 years. Risk factors

included childhood growing pains and hyper-mobility, left elbow fracture, and right kneearthroscopy for osteoarthritis. Her mother hadCharcot-Marie-Tooth disease (the patient, her-self, was self-tested negative). She had extensivedental work and rows of amalgams and root ca-nals. She also had hypertension for 2 years. Herbest exercise tolerance was going on a treadmill1.9 mph for only a few minutes.

Pretreatment: (January, 2002)18/18 TePs. VAS: 9/10 FIQ: 71.7/90

She could not write and could only climb stairs onestep at a time. She could not drive because herneck was stiff and she often felt dizzy. She hadchronic constipation and severe migraines 2 to 3times per month.

Initial treatment included naturopathic evalu-ation and general detoxification (homotoxico-logy approach). After a month of this, shestarted guaifenesin capsules 300 mg per day.This was titrated up to 900 mg BID.July, 2002: 18/18 TePs. VAS: 2-8/10 FIQ:48.4/90.

FIGURE 7. Fibromyalgia patient with “brain fog” improves with neurotherapy/biofeedback.


Overall, she felt 35% improved and was able, forthe first time in years, to play 5 rounds of 9-holegolf. She continued on oral guaifenesin and sali-cylate avoidance.

Jan., 2003: 13/18 TePs. VAS: 1-7/10

She could carry heavy laundry upstairs and exer-cise on a treadmill 3.2 mph for 30 minutes, 3times a week. She was able to do bicep curls with7.5 lbs barbells.

Sept. 9, 2003: 13/18 TePs. VAS: 1-6/ 10 FIQ:12/90

She played 35 rounds of 18-hole golf in the pastsummer. She regularly did heavy gardening andcould sweep her driveway with a heavy broom. Sheonly had light headaches, 1 to 2 times per month.A phone call check on April 21, 2004, revealedcontinued significant symptom reduction and highlevel of function [Fig. 8 ].

The use of CAM must be monitored foradverse effects and potential interactions withmedications. As a general rule of thumb, all herbalproducts should be stopped (blood thinning effect)prior to any surgery or extensive and/or deep soft-tissue injections.

4. Beck Depression Inventory ScoreShould Be Less Than 21/63 Prior toUndergoing CAM Pain Treatments

Higher scores indicated major depression, whichshould be treated first.173 Studies suggest that

patients with FMS or CFS differ from those withmajor depression.174 Axis one psychiatric disor-ders, including “hysteria-conversion disorders,”should also be excluded. Patients involved in stress-ful disability claim appeals and litigation ideallyshould have such issues resolved prior to initiatingtreatment. More detailed evaluation should firstbe completed.175

D. Pain Control Is an Important First-LineGoal in FMS Patients

Patients with mild pain (<4/10) are usually able toparticipate in CAM therapies (including nutrition,exercise, mind-body programs). Those with moresevere pain (>7/10) are often unable to do so andmay require stronger pharmaceutical approachesfirst. This includes long-acting opioids and adju-vants, such as alpha-2 receptor agonists (tizanidine),anticonvulsants (pregabulin, gabapentin), canna-binoids (nabilone). Recent cardiac concerns aboutCox-2 inhibitors have limited use of NSAIDs forchronic pain. As discussed, Botox in patients able toundergo injections may be a safer, well-toleratedapproach to control severe pain.

1. Preinjection (Botox) Screening

Relative contraindications to injection treatmentsinclude

Needle phobiaLack of motivation; unwilling to complyCoagulopathy or use of blood thinnersPregnancyUnstable medical or psychiatric condition

With Botox, injections should not be adminis-tered to patients with flu symptoms, or to thosewho are on aminoglycosides or have neuromuscu-lar junction disorders (Myasthenia Gravis, Eaton-Lambert syndrome, myopathies). It is also recom-mended to not inject into atrophic, flaccid muscles.

If all the above are satisfied, then a furtheroptional screening step is a test TrP injection(s)with preservative-free hydroxide-buffered 1%procaine or lidocaine (see patient profile #4 above).This has the advantage (over regular anesthetics) of

FIGURE 8. Naturopath using electrodermal acupunc-ture technology to assist in this patient’s detoxification.


a much lower likelihood of postinjection soreness /allergic reaction. Patients return after one weekwith a completed pain diary. If there is increasedpain or no pain reduction, then further Botoxinjection should not be administered in the samesites. If there is a significant reduction in pain (VASdecreases over 2 points or by 30%),176 Botox wouldbe indicated. Informed consent and follow-up withvalidated outcome measures are necessary.177

2. Botox Injection Tips

In some patients with dermatographism, a courseof antihistamines prior to and after injections willhelp to prevent flare-ups.178 Recent research sug-gests that higher levels of cytokines in the skin arethe explanation for the skin allodynia found in 27to 38% of patients.179 Vitamin C (500 mg per day)has also been recommended for bruising.180 Anti-coagulants should be discontinued prior to exten-sive needling or injections. Temporary flu-likeillness, lasting a week, is possible. Some patientsnote increased pain, probably from overzealousinjection of numerous TrPs.

For the first-time FMS patient, it is best to go“low and slow.” Only two sites at most should beinfiltrated initially (usually the levator scapulae orpectorals), and, then, further TrP gradually in-jected later. If there is marked skin hyperalgesia,injections should be done quickly (no needling orfanning-out technique) with a smaller gauge needle(27 gauge). Postinjection physiotherapy shouldalso be done.

Patients with marked hypersensitivity, that is,grade 4 tenderness (the grading system recom-mended is: 0= no pain, 1 = complaint of painwithout grimace, 2 = pain with grimace or flinch,3 = pain plus marked flinch or withdrawal, 4 =“untouchable”181) and/or all algometric pain thresh-olds below 2 kg., should first try intradermalinjections. Such patients may actually have gener-alized complex regional pain disorder and aremore likely to flare up if injected too aggressively.Overzealous injections in the painful areas, as wellas unnecessary surgery, cast immobilization of anextremity, and repeated sympathetic blocks (inlate stages) only aggravate this condition.182

Gabapentin slowly titrated up to 2400–3600 mgper day may be more helpful.

3. Inject with Anatomical/BiomechanicalReasoning240,242

• Head: Avoid area above lateral eyebrow (diffu-sion to levator palpabrae and subsequent ptosis)

• Posterior Neck: Avoid suboccipital midline (fora-men magnum) and deep rectus capitis muscles(proprioception disturbed)

• Anterior Neck: Avoid anterior triangle (diffu-sion to swallowing muscles, neurovascular struc-tures). Scalene injections with EMG guidanceonly.

• Shoulders: Avoid scapular stabilizers (rhom-boids, middle and lower trapezius) and su-praspinatus (results in loss of arm abductionability). Minimize upper trapezius injectionsin dropped scapula (upper edge well below T2)(Fig. 9).

• Thoracic: Avoid iliocostalis and longissimusthoracis in kyphotic patients.

• Low back: Avoid lumbar paraspinals inhyperlordosis.

• Spine: Avoid midline (inadvertent intrathecalentry).

• Limbs: Watch dosage. Too high a dose willaffect function, for example, quadriceps andgait, forearm extensors and finger/wrist exten-sion, grasp.

Other precautions with Botox injections:Scalenes and other accessory respiratory

muscles: asthma, chronic obstructive pulmonarydisease, sleep apnea (note that 44% of males withFMS have underlying sleep apnea).240

Pectorals: breast implants, pacemakersHypermobility: Inject only the pericranial

muscles initially(avoid destabilizing the spine)(27% of FMS females have hypermobile jointsyndrome).241

Avoid open wounds, shunts, deep injectionsnear viscera, pleura.

E. Long-Term Managementof Fibromyalgia

There is no universal “magic bullet” for the treat-ment of FMS. It is a syndrome and not a specificpathological disease entity. Diagnosis is made by


exclusion (the usual lab tests are all negative).Symptoms may last an average of 15 years.183

Review papers suggest that positive outcomes oc-cur not only with age184 but also with an adequatephysical activity level185 and coping skills.186 Ex-cess major negative life events and permanentdisability pensions are associated with a negativeoutcome.187 Younger age of onset and less sleepdisturbance are associated with a more favorableoutcome. 188 Effective management is best withan interdisciplinary approach 189–191 emphasizinglifestyle improvement (“TENSQ”: Toxin elimi-nation, Exercise, Nutrition, Sleep hygiene, Quiet“de-stress” time) and pain control (ETPS“TENS”192 and other home modalities). FMSsmokers have also been found to have more pain,numbness, global severity, and functional difficul-ties than nonsmokers. 193

Other studies also indicate that 67% of pa-tients experienced migraine prior to the onset oftheir FMS,194 and that 25% of chronic low backpain patients will evolve into FMS.195,196 PerhapsBotox, shown to be effective in these conditionscould also be used to prevent the development ofFMS. After all: “prevention is better than cure.”

V. CONCLUSION

This review has not only summarized publishedpeer-review literature on pain management in thearea of fibromyalgia but has also presented 20years of clinical experience in managing suchpatients. Most studies of CAM effectiveness are ofpoor quality (few are of high quality according tothe Jadad criteria). One recent extensive FMSreview paper listed 433 references.197 Out of this,only 10 references applied to CAM trials. How-ever, it must be realized that CAM (non-drug)clinical trials are often difficult to implement in atrue blinded fashion.198 Research is needed all themore , noting that CAM use is among the highestin this difficult-to-treat group of patients.

As noted in the typical case studies, effectiveCAM therapies include naturopathic medicine,guaifenesin, neurotherapy, and prolotherapy. Per-haps the most promising treatment to date forpain control is the use of Botox. Integrating thistreatment with other CAM approaches may alsobe useful.199 From an evidence-based perspective,there is obviously a need to do a randomizedcontrolled double-blinded study using Botox in

FIGURE 9. Physiotherapist demonstrating dropped left scapula in patient #17 (Botox case series listed above) whosepost-traumatic “FMS” symptoms resolved after 3 injection series combined with appropriate exercise therapy.


FMS. It is hoped that this review will stimulatefurther research in FMS management. Ultimately,“Doing everything for everyone is neither tenablenor desirable; what is done should ideally beinspired by compassion and guided by science, andnot merely reflect what the market will bear.”(from Grimes DA. Primary prevention of ovariancancer (editorial). JAMA, 1993;270:2855).

ACKNOWLEDGMENTS

Dr. Ko would like to thank the following for theirhelp with this review: Michael Jokic (4th-yearUniversity of Toronto student) for his assistance indata collection and in the CAM survey of FMSparticipants and Pablo Diatel BSc(Kin) (Biofeed-back kinesiologist with Global Managed Health-care) for his contribution in assessing patientsbefore and after Botox injections. Further infor-mation and resources are also available on Dr. Ko’seducation website at www.MusclePainRelief.ca.

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APPENDIX

Jadad Criteria for Clinical Trials on Pain Treatment(Adapted from Ezzo J. Pain 2000;86:217–225.)

Evidence for a clinical trial on pain treatment is weighted as follows:

Score 1 for each:

A. Was the study described as randomized?B. Was the randomization scheme described and appropriate (e.g., table of random numbers or

computer-generated randomization not appropriate for alternating allocation, date of birth random-ization)?

C. Was the study described as double blind?D. Was the method of double blinding appropriate?

1. Were patients reported as blinded?2. Was the outcomes assessor reported as blinded?

E. Was there a description of dropouts and withdrawals?

Scoring: A + B + C + D + E = ___/5. A high-quality trial is 3 to 5.

Additional criteria:F. Were co-interventions avoided or controlled for?G. Was compliance satisfactory? (e.g., with home treatments)H. Was the study population adequately homogenous? (conditions of similar etiologies/natural

histories)I. Was the therapeutic time equivalent between groups (similar number and duration of Rx)?

In our review of the literature, high-quality treatment trials were noted for the following references: 67,71, 86, 91, 99–101, 101a, 103, 108, 108a, 132–6, 140, 200–2, 204–5, 213, 217, 220, 223–4, 228–39.

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