European Journal of Pain 15 (2011) 691.e1–691.e8

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European Journal of Pain

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The menacing phantom: What pulls the trigger?

Melita J. Giummarra a,⇑, Nellie Georgiou-Karistianis a, Michael E.R. Nicholls b, Stephen J. Gibson c,d,Michael Chou d, John L. Bradshaw a

a Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australiab School of Psychology, Flinders University, Bedford Park, South Australia, Australiac National Ageing Research Institute, Parkville, Victoria, Australiad Caulfield General Medical Centre, Caulfield, Victoria, Australia

a r t i c l e i n f o

Article history:Received 7 October 2010Received in revised form 23 December 2010Accepted 15 January 2011Available online 11 February 2011

Keywords:Phantom painTriggersEnvironmentWeatherEmotional distressCoping behavior

1090-3801/$36.00 � 2011 European Federation of Intdoi:10.1016/j.ejpain.2011.01.005

⇑ Corresponding author. Address: Experimental NeuSchool of Psychology and Psychiatry, Monash UniversiVIC 3800, Australia. Tel.: +61 3 9905 3958; fax: +61 3

E-mail address: melita.giummarra@monash.edu (M

a b s t r a c t

Phantom phenomena are frequent following amputation, but how this often painful experience ismodified or triggered by spontaneous events or sensations often puzzles amputees and cliniciansalike. We explored triggers of phantom phenomena in a heterogeneous sample of 264 upper andlower limb adult amputees with phantom sensations. Participants completed a structured question-naire to determine the prevalence and nature of the triggers of phantom phenomena. The four cate-gories of triggers identified include: (a) a quarter of participants experiencing psychological, emotionalor autonomic triggers; (b) half experiencing behavioral triggers, ‘‘forgetting’’ the limb’s absence andattempting to use the phantom; (c) one-fifth experiencing weather-induced triggers; and (d) one-thirdexperiencing sensations referred from parts of the body. Upper limb amputees; and were more likelyto experience weather-induced phantom phenomena than lower limb amputees; and upper and lowerlimb amputees were equally likely to experience referred sensations from the genitals, contradictingthe homuncular remapping hypothesis. Traumatic amputees were more likely to report emotionaltriggers. Further, while those with emotional triggers exhibited poorer acceptance of the limitationsof amputation, they were more likely to employ adaptive coping mechanisms. Finally, habitual ‘‘for-getting’’ behaviors were most common soon after amputation, whereas other more adaptive schemata(e.g., self-defense) were equally likely to be performed at any time following amputation. Variouslikely inter-related mechanisms are discussed in relation to phantom triggers. Ultimately, optimizingstump and neuroma management, as well as restoring function of central networks for pain, limbmovement, and amputation-related memories, should help manage spontaneously triggered phantomphenomena.

� 2011 European Federation of International Association for the Study of Pain Chapters. Published byElsevier Ltd. All rights reserved.

1. Introduction

Many amputees continue to feel a limb following amputation asa phantom, either constantly, or occurring randomly (Giummarraet al., 2010). The phantom is often, but not always (Lacoux et al.,2002), perceived to be painful (Kern et al., 2009; Wartan et al.,1997). Episodes of phantom pain can be triggered or modified byexternal or internal sensory experiences. While many mechanismsassociated with triggering phantom phenomena have been identi-fied, systematic investigation into the prevalence of these triggersis lacking.

ernational Association for the Stud

ropsychology Research Unit,ty, Wellington Road, Clayton,9905 3948..J. Giummarra).

One of the few studies to systematically investigate phantomtriggers surveyed only child and adolescent amputees (Wilkinset al., 2004), and identified many physical, emotional and environ-mental triggers of phantom pain and sensation. Investigations ofphantom triggers in adults are lacking. The nervous system isnow recognized as retaining plasticity beyond adolescence, whichis particularly apparent through the ever-changing phantom sen-sations experienced following amputation in adulthood. Manyneurological and psychological changes occur post-puberty andduring adulthood, however, that may impact on experience of pain,health and trauma. For example, heightened sensitivity to pain,and physiological changes that modify the effectiveness (e.g.,absorption and bioavailability) of pharmaceutical agents (Gibsonand Weiner, 2005); modified emotional wellbeing and coping style(Goyen and Anshel, 1998); altered hormonal and neurotransmitteractivity; and brain plasticity (McCutcheon and Marinelli, 2009;Mercado, 2008; Raz and Rodrigue, 2006). Furthermore, cause of

y of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

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amputation typically differs between children and adults. Adultamputees predominantly present with vascular disease anddiabetes etiology, compared with child amputees who predomi-nantly present with cancer and trauma etiology. Therefore, an ac-count of phantom triggers in adult amputees is warranted toinvestigate the impact of factors typically experienced only inadulthood (e.g., vascular problems or diabetic neuropathy) onphantom triggers.

To provide this much needed account, we systematically ex-plored, quantified and categorized triggers of phantom phenomenausing questionnaires in a large, heterogeneous sample of adultamputees who experience phantom sensations. In this paper, theterms phantom phenomena and phantom sensations are used inter-changeably to encompass the perception of any type of phantomsensation. The terms ‘‘phantom pain’’, and ‘‘non-painful phantomsensations’’ are used to specify the exact type of phantom phenom-ena. While we asked amputees to describe their own phantomsensation triggers through open-ended questions—rather than toselect, via checkbox, those already recognized in the literature—we expected participants to indicate triggers from environmental,emotional, and physical factors (e.g., referred sensations from stim-ulation of the stump, amputated limb or other body parts). We alsoexplored the phenomenological ‘‘motoric’’ experience of the phan-tom limb, and its relation to behavioral stimuli through executionof ‘‘forgetting’’ behaviors. That is, the spontaneous or reflexiveemployment of motor schemata, resulting in attempted use of thephantom limb to communicate (e.g., wave), or interact with objects(e.g., answer the phone or kick a ball). We expected that the perfor-mance of forgetting behaviors would differ over time due to modi-fications in body schemata. For example, ‘‘habitual’’ behaviorsshould only be performed initially; however, other schemata (e.g.,self-defense) should be performed equally at any time followingamputation. We further examine and discuss mechanisms and fac-tors that would be expected to be associated with phantom triggersfrom the study findings (e.g., cause and level of amputation, vasculardisease, coping strategies, anxiety and depression).

2. Method

2.1. Participants

Two hundred and sixty-four amputees experiencing phantomphenomena (either phantom limb awareness, non-painfulphantom sensations or phantom pain) participated, aged 22–96(mean = 59; SD = 15), who had been amputees for between9 days and 70 years (median = 11.5 years, mean = 18 years; SD =17 years). One hundred and eighty-one participants were recruitedfrom Caulfield General Medical Centre’s amputee outpatientsdatabase, and 83 volunteered following media reports on the study.

The participants were predominantly males (n = 197; 75%) withlower limb amputation (n = 219; 83%). Cause of amputation in-cluded trauma (n = 133; 50.4%), vascular disease (n = 49, 18.6%),cancer (n = 25; 9.5%), infection/gangrene (n = 19; 7.2%), diabe-tes(n = 23; 8.7%), congenital limb deficiency (n = 1; 0.4%) or correc-tion of congenital limb deficiency (n = 5; 1.9%), and other (n = 9;3.4%). Seventy-two (27.3%) perceived non-painful phantom sensa-tions only (PLS), 57 (21.6%) perceived phantom pain only (PLP) and135 (51.1%) perceived both PLS and PLP.

2.2. Materials

Questionnaires assessed participants’ neurological (e.g., stroke,peripheral neuropathy or movement disorders), psychological,and surgical histories. The Changes in Body Sensation Following LimbLoss questionnaire (published as online supplementary material)

was developed for the present study, following appraisal of the lit-erature on phantom limb phenomena, to explore aspects of phan-tom limb experience (e.g., perception of the size, shape and postureof the phantom) that had not previously been quantified in a largesample of amputees. The overall questionnaire is long, time con-suming, and ultimately most useful when implemented in themanner for which it was designed: as an exploration of the percep-tion of somatic and other qualities in the phantom limb followingamputation, not as a clinical or diagnostic tool. While the question-naire did not include ‘control’ questions, or measures of suggest-ibility, we did contact nearly all participants for a follow-uptelephone interview to verify their answers.

The overall questionnaire was implemented alongside existingpain (e.g., McGill Pain Questionnaire (Melzack, 1975) and the BriefPain Inventory (Cleeland, 1989)), coping (e.g., Coping StrategiesQuestionnaire (Rosentstiel and Keefe, 1983)), mood (e.g., hospitalanxiety and depression scale (Zigmond and Snaith, 1983)) andamputation scales (e.g., Trinity Amputation and Prosthetics Experi-ences Scales, modified to be suitable for both upper and lower limbamputees (Gallagher and MacLachlan, 2000)). We report only partof the results from the larger questionnaire study; other indepen-dent findings are described elsewhere (Giummarra et al., 2010, inpress). The following questions from the questionnaire were usedin the current study (in addition to the above-mentioned scales):

(a) Information about limb loss including: dates of amputa-tion(s); side and level of each amputation; cause of limb loss,and duration and nature of functional impairment prior toamputation.

(b) Information about phantom sensations and pain, including:phantom limb perception; when the phantom was first per-ceived following limb loss and whether this appeared to berelated to an event/trigger; frequency of phantom limb per-ception now and in the past (always, a few times an hour,day, week, month, year or very infrequently); duration ofphantom limb perception now and in the past (seconds,minutes, hours, days, constantly); perception of the parts,size, shape and posture of the phantom limb; static anddynamic changes in size or shape of the phantom limb (tele-scoping); exteroceptive sensations in the phantom limb(including perception of itching, touching, pressure, vibra-tion, electric sensations, or temperature in the phantom);sensations referred to the phantom limb from parts of thebody; triggers of phantom pain and sensations; movementof the phantom (in particular, whether the phantom movesspontaneously, reflexively or voluntarily); perception of painin the phantom, stump or residual limb now or in the past;visual analog scale for current, and usual (during a typicalepisode of pain), intensity of phantom pain; visual analogscale for current, and usual (during a typical episode of pain),intensity of stump pain. Visual analog scales comprised aline 10 cm long, with the left-most side labeled ‘‘no pain’’and the right-most side labeled ‘‘worst possible pain’’.

2.3. Procedure

All participants gave written informed consent. The study wasapproved by local university and hospital ethics boards, and metthe ethical standards laid down in the 1964 Declaration of Helsinki.Participants were primarily recruited from the Caulfield GeneralMedical Centre amputee outpatients database, Australia. One thou-sand amputees were invited to take part, of whom 249 expressedinterest in participating, and 199 returned valid questionnaires(20% response rate, which is not unusual for amputee research,conducted via mail; e.g., see: van der Schans et al. (2002)). Of these,181 had phantom sensations (painful and/or non-painful) and

M.J. Giummarra et al. / European Journal of Pain 15 (2011) 691.e1–691.e8 691.e3

were retained for analysis in the present study. The sample likelycomprised a larger proportion of upper limb and traumatic ampu-tees than in the general amputee population, but is otherwise typ-ical of the larger population of amputees perceiving phantom limbsensations.

The study was also reported in various Australian media(including mainstream television news programs, and mainstreamand regional newspapers) and resulted in another 108 amputeesvolunteering, of whom 83 who perceived phantom sensations(painful and/or non-painful) returned valid questionnaires. Ques-tionnaires were mailed to participants to be returned to theresearchers in a reply-paid envelope. The researchers then con-tacted each participant to clarify any ambiguities and verify theirresponses.

2.4. Statistical analyses

Univariate {2 and Fisher Exact Tests were used to analyze theassociations between dichotomous variables. Other analyses in-cluded t-tests, principal components analysis, and correlations(Spearman’s Rho). Factors potentially associated with triggers ofphantom phenomena (movement triggers; psychological, emo-tional and autonomic triggers; environmental triggers; and re-ferred sensations) were examined. These included: cause of limbloss (trauma, vascular, diabetes), time since amputation, level oflimb loss (upper versus lower limb; as well as level of loss in therespective limb), anxiety, depression and coping style.

Ideally, we would have liked to distinguish between triggers ofphantom pain and triggers of phantom sensation in all of our anal-yses. However, even though we provided clear definitions on thevarious types of phantom phenomena at the start of the question-naire, participants often either noted that they could not distin-guish between triggers of painful and non-painful sensations, orwere inconsistent in describing the quality of the triggered sensa-tions. As such, we analyzed the reports of triggered phantom phe-nomena collectively, unless specified in the results as relating totriggers of painful or non-painful phenomena.

3. Results

Over half (n = 138, 52.3%) of participants who ever felt a phan-tom, first felt sensations immediately after amputation, wakingfrom surgery or coma, or when sedation/pain relief medicationhad worn off. Some reported that their phantom emerged up to42 years following amputation. Of the 47.7% who did not feel theirphantom immediately, most could not recall a specific trigger fortheir phantom pain onset. The man who first felt phantom pain42 years following amputation had bowel cancer, hemicolectomy,subsequently developed a blood clot in the stump and underwentchemotherapy. Others reported phantom pain onset after an infec-tion in the stump or undergoing ‘‘coning’’ of the stump in prepara-tion for prosthesis fitting, or prosthesis fitting itself.

We now report spontaneous triggers of phantom phenomena,reported by 164 (62.1%) of participants, under the categories of(a) psychological, emotional or autonomic triggers, (b) behavioral‘‘motor schema’’ triggers, (c) influence of the in the weather, and(d) sensations referred from parts of the body (for an overall sum-mary, see Table 1).

3.1. Psychological and emotional triggers

Sixty-one participants (23.1%) reported psychological and emo-tional triggers of their PLP (see Table 1). Twenty-one participantsreported more than one of these triggers. While the nine lowerlimb amputees who reported that their PLP was triggered in empa-

thy for others in pain have been discussed elsewhere (Giummarraand Bradshaw, 2008), we note them here as they represent uniquetriggers of phantom pain.

Traumatic amputees (n = 38, 62.3%) were more likely to reportpsychological or emotional triggers for their phantom than otheramputees (n = 23, 37.7%); p < .05 (1-sided), Fisher’s Exact Test.Depression and anxiety scores on the hospital anxiety and depres-sion scale did not differ between amputees with psychological andemotional triggers and amputees without these triggers. Amputeeswith emotional triggers exhibited increased use of adaptive copingmechanisms compared with those not reporting them. Those withemotional triggers in general (M = 1.4) were less likely to catastro-phize than those without these triggers (M = 2.0); t(119) = 2.02,p < .05, equal variances not assumed. Those whose PLP was trig-gered by heightened emotional distress (HED) were more likelyto use (a) diverting attention coping mechanisms, e.g., ‘‘I think ofthings I enjoy doing’’ [M(HED) = 3.1, M(nHED) = 1.5; t(28) = 4.4,p < .01, equal variances not assumed]; (b) coping self-statements,e.g., ‘‘I tell myself I can’t let the pain stand in the way of what I haveto do’’ [M(HED) = 4.7, M(nHED) = 3.8; t(27) = 2.5, p < .05, equalvariances not assumed]; and (c) behavioral strategies – increaseactivity, e.g., ‘‘I do something active, like household chores or pro-jects’’ [M(HED) = 4.2, M(nHED) = 2.8; t(28) = 3.6, p < .01, equal vari-ances not assumed]. Similarly, those whose PLP was triggered bythinking about the accident were more likely to use attentiondiverting coping mechanisms (M = 3.1) than those without thesetriggers (M = 1.6); t(202) = 2.1, p < .05.

A principal components analysis, with Varimax rotation, wasconducted on responses to the 15 items on the (modified) TrinityAmputation and Prosthetics Experience Scale. The eigenvalues re-vealed four components (Table S2; 10.1016/j.ejpain.2011.01.005,online only), that accounted for 67.6% of the variance in the in-ter-correlation matrix: (1) adjustment to amputation limitations,(2) adjustment to amputee identity, (3) adjustment to being anamputee, (4) a full life as an amputee. Amputees with emotionaltriggers of their phantom (M = .22) exhibited significantly worsescores on factor one ‘the adjustment to the limitations of beingan amputee’ compared with those without emotional triggers(M = �.09) [t(82,225) = 2.0, p < .05, equal variances assumed], indi-cating poorer acceptance of the limitations of amputation. Explor-atory analyses revealed that these differences were specificallyworse for those whose phantom was triggered by emotional and/or physical fatigue; m(no) = �.06, m(yes) = .41; t(29,223) = 2.28,p < .05, equal variances assumed.

.

3.2. Behavioral ‘‘motor schema’’ triggers

One hundred and thirty (49%) participants used their phantomlimb reflexively at some point following amputation, ‘‘forgetting’’that it was not real (see Table 1). Those who ‘‘still forget just asmuch’’ had amputations up to 35 years ago, but generally ampu-tees were more likely to have lost a limb recently (Spearman’sRho = �.24, p < .01). Forgetting was not associated with side ofamputation, or whether the amputated limb was the dominantlimb.

Amputees who report performing a ‘‘habitual behavior’’ withtheir phantom limb, such as trying to walk without putting onthe prosthesis, were much more likely to report doing so soon afteramputation only (n = 64, 69.5%) or to have rarely ‘‘forgotten’’(n = 22, 23.9%); {2(3) = 32.81, p < .001 (2-sided). Other forgettingbehaviors (e.g., behavioral schema, self-defense, utilization behav-ior, response to a perceptual event, the limb is ‘‘needed’’ for a par-ticular behavior) did not show any differences in the frequency offorgetting (i.e., whether forgetting was done soon after amputation

Table 1Frequency of phantom triggers in a group of amputees perceiving phantom phenomena (n = 264).

Type of trigger Frequency (%)

Any trigger 164 (62.1%)Movement and ‘‘behavioral schema’’ triggers 130 (49.2%)Self defense or ‘‘protect the phantom’’ (e.g., to break a fall with the phantom, or move it if someone goes to sit in it’s space) 18 (6.8%)Habitual behavior (e.g., to walk on phantom foot) 95 (36%)Utilization behaviors (i.e., the disinhibited impulse to interact with objects within reach [2], such as putting shoe on phantom foot) 3 (1.1%)Response to a perceptual event (e.g., attempt to scratch an itch or rub a sore spot) 10 (4.2%)Limb is needed for behavior (e.g., while swimming) 4 (1.5%)Gesturing with the phantom (e.g., to wave or gesticulate with the phantom) 3 (1.1%)

Psychological, emotional and autonomic triggers 61 (23.1%)Heightened emotional distress (e.g., stress, anger, depression, panic, fright and frustration) 25 (9.5%)Emotional and/or physical exhaustion 26 (9.8%)Thinking about the amputation/accident 7 (2.7%)Evoking a mental image of the limb 18 (6.8%)Immune response/hormonal effects (e.g., being ‘‘run-down’’, having a fever, cold or the flu) 13 (4.9%)Dietary factors (e.g., high levels of salt, chocolate or dehydration) 2 (.8%)Mental rest or inactivity 7 (2.7%)Empathy for another’s pain (observing or thinking about another in pain, or circumstances that imply pain such as war, blood or accidents) 10 (3.8%)

Influence of the weather 52 (20%)Extreme changes in the weather and storms 30 (11.4%)Cold and/or wet weather 25 (9.5%)Hot and/or humid weather 7 (2.7%)

Referred sensations from the amputated limb 97 (36.7%)Touching the stump 27 (9.9%)Moving stump muscles 6 (2.2%)Applying pressure to the stump (e.g., excessive exercise, lying, sitting) 49 (18.1%)Removing pressure from the stump (e.g., removing the prosthesis) 5 (1.8%)Injury to the stump or ill-fitting prosthesis 13 (4.8%)Upper portion of the limb (e.g., from the sciatic nerve/hip) 5 (1.8%)Fluid retention in the stump 1 (.4%)

Referred sensations from the opposite limb 30 (11.4%)Ache, pain or injury (e.g., get sympathy pains or discomfort in phantom when feeling pain in physical limb) 7 (2.6%)Neuropathy or disability (e.g., limited mobility in the physical and phantom limb) 4 (1.5%)Mirror movements (e.g., phantom foot stretches when the opposite physical foot stretches, or phantom hand mirrors intact hand) 6 (2.2%)Posture/form 2 (.7%)Temperature (e.g., five cold toes equals ten cold toes) 3 (1.1%)Touch/exteroceptive sensations (e.g., being tickled on physical foot is felt also on phantom foot) 4 (1.5%)Itch 1 (.4%)Stimulate contralateral limb to ease discomfort in phantom 4 (1.5%)

Referred sensations from other body parts to phantom arm in upper limb amputees 6 (16.2%)Referred sensations from other body parts to phantom leg in lower limb amputees 36 (17.1%)

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only, rarely, still forgotten sometimes or still forgotten just asmuch).

3.3. Influence of the weather

Fifty-two (20%) amputees reported that their PLP was triggeredor modified by environmental factors and/or changes in the weath-er (see Table 1). Upper limb amputees were more likely to be af-fected by cold/wet [p < .01, 1-tailed, Fisher’s Exact Test] and hot/humid weather [p < .05, 1-tailed, Fisher’s Exact Test] than lowerlimb amputees.

3.4. Sensations referred from parts of the body

Ninety-seven (36.7%) amputees perceived sensations referredto the phantom limb from the remaining portion of the amputatedlimb, and 30 (11.4%) amputees reported perceiving referred or mir-rored sensations from the opposite limb to the phantom (see Table1 for summary). There were no differences in the perception ofreferred sensations from the amputated limb/stump to the phan-tom limb according to cause of amputation.

Six (16.2%) upper limb amputees and 36 (15.6%) lower limbamputees reported perceiving referred sensation from other partsof the body. Upper limb amputees reported sensations referred

from the shoulder blades (n = 1), neck (n = 1), collar bone (n = 1),upper leg, breast and base of skull (n = 1) and toileting or sex(n = 2). Lower limb amputees reported sensations referred fromthe back (n = 11), face (n = 1), ribs (n = 1), hand (n = 1), touch togenitals/groin (n = 5), pelvic pain (e.g., menstruation pain) (n = 1),sex or orgasm (n = 8), full bladder, urinary tract infection or urina-tion (n = 12), defecation/wiping bottom (n = 7), toileting (not de-fined) (n = 4). Sensations triggered by urination/defecationtended to be characterized as tingling, ‘‘icy cold’’ or warm/burningpain in the phantom. Sensations triggered during sex were de-scribed as pain during or after orgasm, tingling, being aware ofphantom limb presence, or that phantom pain was worst on entrybut would ease after a minute or two.

Upper and lower limb amputees were equally likely to experi-ence referred sensation to the phantom from the genitals [p = .21,Fisher’s Exact Test], which contradicts the homuncular remappinghypothesis (Ramachandran, 1993). Time since amputation was notassociated with the likelihood of exhibiting a ‘‘homuncular’’ pat-tern of referred sensations (i.e., upper limb amputees with sensa-tions referred from the shoulder or face, and lower limbamputees with sensations referred from the genitals). There wasno relationship between prior surgery or number of amputationsand the perception of sensations referred to the phantom fromany part of the body.

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4. Discussion

For the first time we report a much needed account of phantomtriggers in adult amputees. While our participants almost univer-sally experienced spontaneous phantom pain or sensations, two-thirds identified at least one trigger that modified their experience:half executed automatic behavioral motor schemata; one-thirdnoted referred sensations to the phantom, a quarter psychologicaland emotional triggers; and one-fifth weather factors. In order toexplore this further we provide a model of mechanisms associatedwith phantom triggers from our findings, together with related lit-erature. This model implicates dysfunction in neurological, psycho-logical and vascular systems as increasing susceptibility tophantom triggers.

4.1. Cortical reorganization and referred sensations

We provide further evidence that perceptual correlates of corti-cal reorganization vary significantly and are not a simple matter ofadjacency of homuncular remapping (Knecht et al., 1998). Whileupper limb amputees tended to report referred sensations fromthe stump or shoulder to the phantom, they also reported sensa-tions referred from the upper leg and genitals. Similarly, lowerlimb amputees report referred sensations not only from the back/hips and genital/pelvic region, but also from the face, ribs andhand. Evidently, cortical reorganization results in strengtheningand weakening of an extensive neural network. Studies with neu-roimaging are required to investigate brain changes in amputeeswith non-homuncular phantom triggers.

Referred sensations from the residual limb to the phantom mayrelate to two main ‘‘central’’ mechanisms. First, cortical reorganiza-tion whereby motor commands retarget stump muscles, and ishighly correlated with phantom pain (Flor et al., 2006). Second,remapping of representations of the phantom limb onto neighbor-ing regions of the somatosensory homunculus result in perceivedreferral of sensation from the stump and nearby regions to thephantom (Flor et al., 1998; Halligan et al., 1993; Ramachandranet al., 1995). Treatments targeting these mechanisms can restoreconventional homuncular organization, including mirror therapy,movement imagery training (MacIver et al., 2008; Moseley,2006), and sensory discrimination training (Flor et al., 2001).

Two key peripheral factors can also result in co-occurrence ofsensations in the residual limb and phantom. First, cramping phan-tom pain correlates with muscle tension in the residual limb (Kernet al., 2009; Sherman et al., 1992), and is relieved by interventionsthat decrease muscle tension (Sherman, 1976). Second, stimulationof stump neuromata—that is, the bundle of nerve cells that formfollowing a nerve lesion—can exacerbate phantom pain (Flor,2002). Amputees should benefit from improved management ofstump pathology (e.g., stump injuries, ill-fitting prostheses) andneuromata. Stump neuromata can be effectively, but not univer-sally, managed by a variety of techniques including injections intonerve endings (e.g., with norepinephrine) to desensitise pain con-duction pathways, or alter the nerve end with silicone caps ortransposing it into muscle or bone (Wu and Chiu, 1999). However,in amputees whose pain is also centrally generated (e.g., due tocentral sensitization), removal of stump neuromata would not sig-nificantly reduce pain. Third, enhanced synaptic responsiveness inthe dorsal horn of the spinal cord (see discussion below) also likelycontributes to the experience of referred sensations (Flor et al.,2006).

Some amputees described sensations referred from the oppositelimb (e.g., pain, neuropathy, movements, touch or itch). Here twomechanisms may operate. First, inter-hemispheric synaptic con-nections between the intact and amputated limbs may become dis-inhibited, and even strengthened, following deafferentation due to

the absence of error signals from the representation of the ampu-tated limb (Frith et al., 2000). Second, afferent feedback from theintact limb may project ipsilaterally onto the representation ofthe amputated limb. These mechanisms may result in motor over-flow (Hoy et al., 2004) and the perception of mirror movements inthe phantom.

4.2. Neurotransmitter activity and peripheral changes

In addition to central ‘‘rewiring’’ changes, deafferentation re-sults in reduced inhibitory control in the dorsal horn, which subse-quently sets a lower threshold to detect afferent impulses arisingfrom neuromata compared with intact body sites (Katz, 1992b).Neuromata emit high rates of ectopic activity and are sensitive toexternal and internal stimulation (Devor, 1997; Katz, 1992a); e.g.,release of sympathetic neurotransmitters noradrenalin, acetylcho-line (Katz, 1992b) and epinephrine (Flor, 2002) during emotionalarousal. Therefore, events that alter neuroma activity may alsoevoke phantom pain, from physical stress to the stump to emo-tional distress.

Many amputees experienced pain and sensations that wereexacerbated by storms and extreme weather changes. A tentativeinterpretation is that these individuals react to electromagneticwaves generated by atmospheric discharges (e.g., lightning). Thishas been suggested to affect serotonin metabolism (Sulman,1980), which is important in descending inhibitory pain pathways,and may alter alpha and beta power (Schienkle et al., 1999). Stumpliners that shield electromagnetic fields (e.g., the medipro�LinerRELAX (Kern et al., 2006), or Farabloc™ (Conine et al., 1993))may reduce phantom pain duration and intensity. However, themechanisms and neural pathways that mediate the effects of elec-tromagnetic waves on nociception are unknown (Del Seppia et al.,2007).

Environmental phantom triggers were consistent with thosepreviously described, including drops in barometric pressure,changes in atmospheric temperature and increases in humidity(Arena et al., 1989; Gorin et al., 1999; Melzack et al., 1997;Mitchell, 1877). More specifically we found that upper limb ampu-tees were more susceptible to fluctuations in atmospheric temper-ature than lower limb amputees, perhaps because upper limbs aretypically more likely to be exposed (i.e., unclothed) to changes intemperature compared with lower limbs. Stump temperature, par-ticularly stump cooling, is associated with reduced blood flow(Flor, 2002; Weinstein, 1998), and vasoconstrictive chilling of thestump may underlie weather-induced phantom pain (Kern et al.,2006). Heat also affects nerve function, particularly in those withnerve lesions (e.g., multiple sclerosis (Syndulko et al., 1996)), andmay also exacerbate the perception of neuropathic sensations inamputees (e.g., tingling or pins and needles).

4.3. Vascular mechanisms

Amputees with vascular disease are more likely to experiencephantom pain (Giummarra et al., 2009), probably from reducedvascularisation and compromised blood flow (Gallagher et al.,2001; Sherman, 1994). Various internal (e.g., emotional) and exter-nal (e.g., environmental) factors may further influence vascularfunctioning. Emotional stress provokes reflex activity in cutaneoussudomotor and vasomotor sympathetic fibers, and may triggertingling ‘‘goose-bump’’ sensations in the amputated limb (Katz,1992b).

4.4. Amputation-related memories

While phantom pain is affected by stress, anxiety and depres-sion as are other pain syndromes (Horgan and MacLachlan,

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2004), isolated psychological and emotional events can trigger orworsen phantom pain (Angrilli and Koester, 2000; Arena et al.,1990; Hill et al., 1996; Katz, 1992b; Melzack et al., 1997;Rasmussen et al., 2009; Salomons et al., 2004; Wilkins et al.,2004); e.g., emotional distress, fatigue, thinking about the amputa-tion, or about others in pain. These triggers were more often re-ported by traumatic amputees. Those with psychological andemotional triggers, particularly emotional and physical fatigue,exhibited poorer adjustment to the limitations of amputation;however, they were more likely to use adaptive coping strategies(e.g., diverting attention and positive self-statements).

Various factors may mediate ‘emotionally’ triggered pain.First, formation and maintenance of memories of the amputationevent and related experiences (e.g., surgery) (Flor, 2008). Thismay result in ‘‘over-consolidated’’ memories (Pitman, 1989),encoding particularly vivid and long-lasting autobiographicalmemories of the event. Consequent exposure to isolated aspectsof those memories could be sufficient to revoke or worsen asso-ciated phantom pain. Second, experience of both trauma andamputation are more likely to result in development of post-traumatic stress disorder (PTSD), and pain triggered by remindersof the trauma (Whalley et al., 2007). This may be mediated byphysiologic and neural systems involved in trauma-related stressresponses (McLean et al., 2005). Core events associated with trau-matic amputation are unexpected and probably more emotion-ally distressing compared with scheduled amputations, causingtraumatic amputees to encode more intense emotional memoriesof the amputation. Third, some individuals may be more prone tosomatise psychological distress, implicating increased efficiencyor amplification of neurological response in various nervousstructures like the limbic system, or peripheral and central partsof the pain pathway (Henningsen, 2003; Katz, 1992b; Melzack,1992). Fourth, the experience of pain that is triggered by observ-ing or thinking about another in pain (synesthesia for pain) mayinvolve disinhibition of pain mirror systems (Giummarra andBradshaw, 2008). That is, neural systems that are active not onlywhen processing pain in oneself, but also in others. Pain synaes-thesia is independent from general emotional distress, and likelyrelates to hyper-vigilance to cues of pain, threat and injury(Fitzgibbon et al., 2010). One suitable treatment of emotionallytriggered pain involves ‘reprogramming’ pain memories relatedto amputation through eye movement desensitization and repro-cessing, which concurrently reduces phantom pain, depressionand PTSD symptoms (Schneider et al., 2008). While we werenot in a position at the time of data collection specifically to testthe above hypotheses, they might be examined explicitly infuture research.

4.5. Engagement of motor schemata

Soon after amputation, the ‘‘intact’’ and ‘‘amputated’’ bodyimages conflict; however, post-amputation physiotherapy, pros-thetics training and everyday demands on the body inevitablyforce amputees to become consciously aware of their limb absence.Consequently, the acquired ‘‘amputee’’ body image adopts motoraffordances (Enticott et al., 2010) to ambulate or manipulate every-day objects with the amputated limb, essentially creating newschemata for the amputated limb. Attempts to reflexively performhabitual behaviors with the phantom limb, such as trying to walkwithout wearing the prosthesis, are most common soon afteramputation or among those who rarely ‘‘forgot’’. However, othermore adaptive schemata (e.g., self-defense) are likely to be per-formed equally at any time following amputation. Automatic ‘‘selfpreservation’’ behaviors may be hard-wired and may be more dif-ficult to ‘‘unlearn’’ considering their evolutionary significance.

5. Limitations

As noted earlier, we would have liked to distinguish betweentriggers of phantom pain and triggers of phantom sensation in allof our analyses. However, participants often noted that triggersof their painful and non-painful sensations were the same, or thesensations themselves were indistinguishable. This limitation ismost pronounced in questionnaire-based studies with open-endedquestioning where it is not always possible to probe participantsfor further information and clarity. As such, we could only analyzereports of triggered phantom phenomena collectively, exceptwhere specified as relating to triggers of painful or non-painfulphenomena. It must also be noted that some participants were tak-ing ongoing medications to treat their phantom pain, includingpain medications and psychotropic compounds, and this may haveimpacted on the frequency and effects of triggers. Finally, over fiftypercent of the participants in the current study underwent trau-matic amputation. This may have had a disproportionate effecton the frequency and effects of phantom triggers, particularly psy-chological and emotional triggers, which we note above.

6. Conclusions

In summary, phantom phenomena are common followingamputation, and can be modified or triggered by a range of eventsand sensations. A number of key, probably inter-related, mecha-nisms are likely to be involved. First, spontaneous activity withinneuromata and the release of various neurotransmitters (e.g., nor-adrenalin, acetylcholine, and epinephrine) during emotional orenvironmental triggers. Second, stump injury, temperature, circu-lation and sensitivity to atmospheric or environmental distur-bances (e.g., barometric pressure). Third, referred sensations andcortical reorganization. Fourth, physiological storage of amputa-tion-related memories, pointing to limbic system involvement.And finally, automatic engagement and maintenance of body sche-mata. We suggest that optimizing stump and neuroma manage-ment, as well as restoring the function of central networks forpain, limb movement, and amputation-related memories, shouldhelp manage spontaneously triggered phantom phenomena.

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Table S2Component loadings for principal components analysis, with varimax rotation, for the Trinity Amputation and Prosthetics Experiences Scales.

Component

Item description 1: Adjustment toamputation limitations

2: Adjustment toamputee identity

3: Adjustment to beingan amputee

4: A full life as anamputee

h2

My limb loss interferes with the ability to do my work .79 .65Being an amputee makes me more dependent on

others than I would like to be.75 .63

Being an amputee limits the kind of work that I can do .84 .72Being an amputee means that I can’t do what I want to

do.80 .67

Being an amputee limits the amount of work that I cando

.85 .75

I don’t care if somebody looks at my stump .82 .73I find it easy to talk about my limb loss .88 .85I don’t mind people asking about my limb loss .88 .83I have difficulty in talking about my limb loss in

conversation.59 .42

I don’t care if somebody notices that I am an amputee .727 .55I have adjusted to having lost my limb .81 .73As time goes by, I accept my limb loss more .85 .76I feel that I have dealt successfully with this trauma in

my life.79 .73

I am used to being an amputee .36 .19Although I am an amputee, my life is full .96 .93Rotated eigenvalues 4.68 3.16 1.29 1.02Percentage of variance 31.17 21.07 8.57 6.77

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