A Prospective Study of Factors Associated With the Presence of Phantom Limb Pain Six Months After Major Lower Limb Amputation in Patients With Peripheral Vascular Disease

The Journal of Pain, Vol 8, No 10 (October), 2007: pp 793-801 Available online at www.sciencedirect.com

A Prospective Study of Factors Associated With the Presence of Phantom Limb Pain Six Months After Major Lower Limb Amputation in Patients With Peripheral Vascular Disease Cliff Richardson,* Sheila Glenn,* Maureen Horgan,* and Turo Nurmikko† *Liverpool John Moores University, and † University of Liverpool, Liverpool, United Kingdom.

Abstract: Because of a lack of evidence to support any treatment for phantom limb pain (PLP), interest has turned to preventing it instead. However, like other areas of PLP research, there is little consensus regarding factors that may be associated with the development of PLP. This study was devised to identify physical and psychological factors associated with PLP development and maintenance. It was a prospective study of 59 patients listed for amputation of a lower limb due to peripheral vascular disease. Each was interviewed before amputation, and the survivors were reinterviewed 6 months afterward. Pain and coping style were the primary outcome measures. The use of high levels of passive coping strategies (P ⴝ .001), especially catastrophizing (P ⴝ .02) before amputation, were found to be associated with PLP development. Pain was only weakly associated with the presence of PLP 6 months after amputation. The ability to move the phantom (P ⴝ .01) and stump pain (P ⴝ .01) were postamputation factors associated with PLP. The complexity of the relationship between previous pain and coping style and the development of PLP is discussed alongside aspects of pain memory. Pre-emptive treatment of PLP will need to include psychological as well as physical interventions. Perspective: During this study, preamputation passive coping (especially catastrophizing) was found to be associated with the development of PLP. This knowledge will help researchers and clinicians to identify future targets for pre-emption of this condition because once established, PLP is difficult to treat. © 2007 by the American Pain Society Key words: Phantom limb pain (PLP), coping, passive coping, catastrophizing, peripheral vascular disease.

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hantom limb pain (PLP) occurs in 50% to 80% of limb amputees.11,43,60 When present, it is difficult to manage. More than 50 different treatments have been developed for PLP, yet most have been unsuccessful.20,68 Interest has therefore turned to prevention or pre-emption. Physical and sociopsychological factors have been hypothesized to be associated with PLP devel-

Received November 2, 2006; Revised May 3, 2007; Accepted May 15, 2007. This study was funded as a PhD project by Liverpool John Moores University and The Pain Relief Foundation, Liverpool, United Kingdom. Address reprint requests to Dr. Cliff Richardson, University of Manchester, School of Nursing, Midwifery, and Social Work, Gateway House, Piccadilly South, Manchester, M60 7LP, UK. E-mail: clifford.richardson@ manchester.ac.uk 1526-5900/$32.00 © 2007 by the American Pain Society doi:10.1016/j.jpain.2007.05.007

opment for 20 years51; however, few have been rigorously investigated; hence, targets remain elusive. Evidence that preamputation pain is associated with the development of PLP arises from animal1,36,40,41 and human experimentation.21,38,63 Some have even argued that PLP is a memory of preamputation pain,28,35,38,56 a theory that may be supported by the presence of superadded phantom sensations (where the PLP mimics a previous pain, ie, pain from a preceding ingrowing toenail) in some amputees.35,38,48,74 The memory theory is being challenged however, as 1 prospective study of lower limb amputees52 found no comparisons between the descriptors chosen or the intensity of preamputation and postamputation pains, and an epidemiological study43 of upper limb amputees found no relationship between the pain before the amputation and the onset of PLP (P ⫽ .59). 793

794 Despite this, multiple studies have tried to reduce the incidence of PLP by preempting the preamputation pain.5,8,13,14,17,29,34,44,52,55,64 The conclusion from these studies is that controlling pain before amputation does not prevent the development of PLP.54 Further endorsement of this comes from a stepwise logistic regression to identify risk factors associated with PLP in a group of 536 amputees from a limb-fitting center.11 Preamputation pain was not identified to be 1 of the risk factors. The conflict between the identification that preamputation pain is associated with the presence of PLP but its preemption fails to prevent PLP suggests that PLP is a complex phenomenon53 and that its preemption may need to involve more than pain control. Emotional states, including anxiety and depression, have been suspected to predispose, trigger, and/or maintain PLP.9,15,22,23,59,68 Evidence for this is inconsistent. In a group of 50 British war veterans,45 it was found that PLP was unaffected by war memories and although unhappy memories increased the number of words chosen from the McGill Pain Questionnaire this was not statistically significant. A separate study found no link between PLP and anxiety, depression, and emotional adjustment, including the grieving process.18 It has been found, however, that PLP could be triggered by emotional events26 and that when faced with psychological stress, amputees with PLP react physiologically differently from amputees who do not have PLP.2 Personality and family support are also thought to be important both as predictors for the onset of PLP and as potential targets for intervention.6,10,27,62,72 Full elucidation of these traits and their relationship to PLP has yet to be explored. A clearer link has been identified between coping style and PLP. Specifically, when using the Coping Strategies Questionnaire (CSQ)61 the “helplessness” factor and catastrophizing subscale are found in high levels in amputees with PLP.24,25 It is unknown whether this situation existed preamputation or whether it is a result of the presence of PLP. Catastrophizing has been broadly defined as the exaggerated orientation toward the pain stimuli and is associated with a heightened pain experience.61,71 It is known to be associated with high reported pain intensity and disability67,71 and in the development of some chronic pain conditions.49,66 Within the periamputation period there are neuroplastic changes, associated with PLP development,3,19,42,58 which occurs at the same time as the amputee is having to cope with pain, the disfiguring surgery, and the rehabilitation. The coping cognitions including catastrophizing associated with these events may well have a potential to affect the cortical reorganizations, giving them the potential to be part of the cause or maintenance of PLP; hence it would be useful to find out if preamputation as well as postamputation coping is linked to PLP. Some postamputation factors have also been found to be associated with PLP. It has been suggested that there is an inverse relationship between telescoping (the gradual reduction in size of the phantom) and phantom pain.31,35,39 Induced telescoping has produced a reduction or complete cessation of phantom sensation and

Factors Associated With Phantom Pain Development phantom pain.37,50,57 One study specifically designed to explore this phenomenon, however, did not identify a difference between the presence of telescoping and the absence of PLP.50 Some studies have reported that PLP, phantom sensations (PS), and stump pain (SP) are correlated.11,69,73

Summary Identifying factors associated with PLP in amputees is problematic because most, if not all, could have been caused by, rather than contributing to PLP. Once present these factors may assist in the prolongation or continuation of the PLP, but may not have been part of the original cause. Previous studies often include upper and lower limb amputees of surgical and traumatic origin with significantly varying durations since amputation. Consistency has been further hindered by a lack of prospective research in this area. The present study was designed to tackle these challenges. It aimed to investigate pre and postamputation factors (especially pain and coping style) that may be associated with the development and or maintenance of PLP, within an homogenous group of patients undergoing amputation of a lower limb for peripheral vascular disease (PVD).

Research Questions 1. What preamputation and postamputation factors are associated with PLP? Previous studies had focused only upon PLP presence; this study explored PLP presence, intensity, and duration. The hypothesis was that high levels of preamputation pain and coping would be associated with greater incidence, intensity, and duration of PLP. It was also hypothesized that other postamputation phenomena would also be associated with these preamputation factors. Confirmation of the link between PLP and stump pain and telescoping was sought. 2. Are there similarities between pre and postamputation pain? Here the memory theory was being tested. The hypothesis was that preamputation pain would be different to PLP.

Materials and Methods The university and the local medical research ethics committees approved the study.

Study Design In an attempt to maintain homogeneity in the sample, a prospective study of patients with PVD requiring major lower limb amputation was undertaken. All participants gave written consent, and were interviewed before surgery and 6 months after surgery.

Sample Patients were recruited from 1 hospital in a city in the North West of England. All patients consented for above or below knee amputation due to PVD were included. All patients were given oral analgesia before the surgery

ORIGINAL REPORT/Richardson et al and were routinely listed for their surgery. As this was a teaching hospital, the surgery may have been performed by a trainee or a consultant vascular surgeon. Patients were excluded if they refused consent, were confused or were unable to communicate in the preamputation interview.

Instruments Preamputation All participants had their age, PVD history, and type of surgery (above or below knee amputation) recorded. The following questionnaires were used during a patient interview after the decision to amputate had been made. In recognition of the severity of their illness at this time, the number of questionnaires was kept to a minimum and short forms used when available.

Pain The short form McGill pain questionnaire (MPQ),47 was used to measure current and worst pain from the ischemic leg. This questionnaire includes a 0- to 100-mm visual analog scale (VAS), present pain intensity (PPI), and a list of pain descriptors. Each descriptor is assessed for its intensity on a 0 –3 scale (0 ⫽ none, 1 ⫽ mild, 2 ⫽ moderate, and 3 ⫽ severe). The descriptors are recorded as a total number chosen and then converted into 2 subscales (sensory and affective). Sensory words describe the pain itself, whereas the affective words describe the affect that the pain has on the sufferer. Additionally, all participants were asked about the duration of their ischemic pain.

Coping The Coping Strategies Questionnaire (CSQ)61 was used. This comprises 44 items and 7 subscales (diverting attention, reinterpreting the pain sensation, catastrophizing, ignoring sensations, praying and hoping, coping selfstatements, and increased behavioral activities). Total scores and all subscales scores were calculated. Previous principle component analyses have identified varying broad factors within the CSQ. In all cases, 3 factors were identified, however, these were named differently and included variations of subscales.24,25,61 One consistency was the use of the word “helplessness” for 1 of the factors. This factor always included catastrophizing however the other subscales within it changed. It is recognized, however, that the term helplessness is now being used as 1 component of the catastrophizing scale, which can therefore lead to confusion. In an attempt to avoid confusion, this study chose to separate the subscales into passive and active coping styles.4 Passive coping includes catastrophizing and “praying and hoping,” whereas active coping includes the other 5 subscales of the CSQ.

Postamputation (6 Months) All survivors were interviewed 6 months after the amputation, which corresponds to a time when all acute postoperative stump pain should have resolved and when PLP would be deemed to be chronic. This time

795 period allows for the crystallization of new neurological networks and has been used in PLP studies before.30,52,53 A phantom phenomena questionnaire was devised that asked about postamputation phenomena previously identified in the literature. These were phantom sensations (present/absent), kinetic sensation (able to move phantom, yes/no and phantom moves on its own, yes/no), kinesthetic sensation (phantom is oriented to normal position for absent limb, yes/no; if no describe orientation), exteroceptive sensations (description of sensation, ie, pins and needles), super-added sensations, PLP, and stump pain. As with previous studies, the presence of these phenomena including PLP was self assessed by the participant, however, due to the overlapping nature of many of these phenomena, the interview allowed elucidation and ensured that all postamputation experiences were recorded as accurately as possible. For instance, a commonly reported issue is the ability to recognize PLP and separate it from stump pain. In this study, the interviewer could elaborate and make sure that these were differentiated. If PLP was present, its intensity, frequency and, if not, continuous, average duration was determined, and the MPQ (current and worst PLP), and CSQ were additionally completed.

Statistical Analysis Associations between preamputation phenomena and PLP were investigated by using the Fisher exact test, t tests, 2-way repeated-measures ANOVAs, and Pearson correlations, depending on the data. Visual inspection of individual pain descriptors was performed to investigate the potential pain memory theory. Cross-tabulations, correlations, and simple regression analyses were performed to explore associations between all elements of PLP and to investigate the potential for a composite predictive score for PLP development, intensity, and frequency. Because of the sample size, logistic regression analysis was not possible.

Results Seventy-seven patients were referred over a 29month period, and 59 (77%) were recruited into the study (Fig 1). The general details of the patients are shown in Table 1. Fifty-two amputees completed the 6-month interview. Forty-one patients (78.8%) reported PLP at 6 months, which is similar to previous studies.11,43 Of the 11 who had no PLP at the 6-month interview, 4 indicated they had not experienced any PLP after the amputation, and 7 stated that they had experienced PLP for weeks or months, but it had completely disappeared by the time of the interview. Pain tended to be intermittent, with only 1 (2%) complaining of constant pain and 65.3% reporting episodes of less than 30 minutes’ duration. Sixtyfour percent had at least 1 attack a day, and 12% more than 10 attacks per day. All patients, including those without PLP, reported phantom sensations.60 The details of the postamputation phenomena are presented in Table 2. In the following sections, various

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Factors Associated With Phantom Pain Development Table 2. Reported of Phantom Phenomena at Six Months After Amputation

Figure 1. Flow chart for study.

statistical relationships are identified, however, due to the nature of the calculations, none can be seen as causal. In order to relay this noncausal relationship, the word “associated” is used to describe this connection between the factors.

Preamputation Factors Associated With PLP Pain Associations were found between PLP presence (but not intensity or duration at 6 months) and preamputation pain intensity as measured by PPI (current; t ⫽ 2.24, df 50, P ⫽ .03: worst; t ⫽ 3.20, df 11.54, P ⫽ .01) and worst VAS (t ⫽ 2.23, df 11.29, P ⫽ .05). Also, the use of the word “tender” to describe preamputation pain (t ⫽ 4.01, df 38.56, P ⫽ .0001) was associated with PLP presence but not with PLP intensity, duration, or regularity at 6 months. Odds ratio calculations suggest that this association should be viewed with caution (Table 3). The dura-

Details of Participants Undergoing Major Lower Limb Amputation Due to PVD

Table 1.

Gender Age (years) Cause of PVD

Level of amputation

Time in pain (months)

Male Mean (SD) Smoker Diabetes Smoker and diabetes Chronic ulceration Frostbite Unknown Below knee Above knee Bilateral below knee Bilateral above knee Mean (SD)

63.3% 63.8 (10.4) 31.7% 35.0% 25.0% 3.3% 1.7% 3.3% 45.8% 49.1% 3.4% 1.7% 13.0 (21.5)

PHENOMENON

PERCENTAGE

PLP PLP position Toes Foot Lower leg Whole leg Combination Phantom sensations Telescoping Phantom corresponds to missing leg Phantom moves itself Phantom can be moved Exteroceptive sensations Total Pins and needles (% of total) Itch (% of total) Super-added sensations Stump pain

78.8 14.6 52.1 22.9 4.2 6.2 100.0 67.3 88.5 65.4 58.0 51.9 50.0 42.9 15.4 51.9

tion of pain before amputation (t ⫽ 1.71, df 50, P ⫽ .09) and the other pain descriptors (t ⫽ 0.08 –1.91, df 17– 49, P ⫽ .12–.94) were not found to be associated with the presence of PLP. The finding that the use of “tender” to describe the preamputation pain was associated with PLP was further explored to test its positive and negative predictive values. Sixteen participants chose tender at level 2/3 for their current pain before the amputation and all of these (100%) had PLP at the 6-month interview, similarly 21/22 (95%) who chose tender at the same level to describe their worst preamputation pain had PLP. However, 46% of participants who did not choose tender to describe their preamputation pain also had PLP 6 months after amputation, although of the 11 who did not have PLP at the 6-month interview only 1 described their preamputation worst pain as moderately tender and 1 mildly tender.

Table 3. Odds Ratios and Confidence Intervals for Factors Found to Have Association With PLP Presence Six Months After Amputation FACTOR

P VALUE

OR

95% CI

wVAS cPPI wPPI Tender CSQ total Passive coping Catastrophizing Praying/hoping Smoking Stump pain Able to move phantom

.05 .03 .01 .0001 .02 .001 .02 .01 .04 .02 .01

7.37 0.54 0.46 0.30 12.76 4.60 3.28 2.86 0.19 7.03 8.31

0.28–32.61 0.13–2.30 0.44–2.36 0.61–1.84 6.58–57.86 6.50–25.00 1.71–14.91 1.68–13.18 0.04–0.85 1.34–36.82 1.54–44.79

Abbreviations: wVAS, worst preamp VAS; cPPI, current preamp present pain intensity; wPPI, worst preamp present pain intensity.

ORIGINAL REPORT/Richardson et al Although 15.4% of the sample identified super-added sensations, none of them were painful. In all cases, these were the feeling that the leg was clothed such as wearing trousers or a sock.

Coping Preamputation total CSQ score (t ⫽ 2.52, df 50, P ⫽ .02), and passive coping style (t ⫽ 3.42, df 50, P ⫽ .001) showed association with PLP presence but not intensity, duration, or regularity of PLP at 6 months. No association was found between preamputation active coping style and PLP presence (t ⫽ 1.45, df 50, P ⫽ .15). No significant correlations were found between preamputation coping (active and passive) and PLP intensity, duration or regularity. The 2 CSQ subscales that make up passive coping, catastrophizing (t ⫽ 2.53, df 50, P ⫽ .02), and praying/hoping (t ⫽ 2.60, df 50, P ⫽ .01), were both found to be associated with the presence of PLP. Catastrophizing was also found to be correlated with PLP regularity (r ⫽ ⫺0.33; P ⫽ .02). This negative correlation may at first appear contradictory; however, reduced regularity may mean longer duration for each episode of PLP. A calculation combining regularity and duration would have allowed resolution however this was not possible due to the way that these figures were recorded. Odds ratio calculations strengthen the positive associations found between coping style and PLP (Table 3). Cross-tabulations were performed to identify passive coping scores above which the risk of developing PLP becomes high risk. Patients with preamputation scores above 38 (maximum score 72) were more likely to develop PLP (P ⫽ .001). Further calculations were not possible due to low numbers.

Other Associations Smokers (Fisher exact, P ⫽ .04), the presence of stump pain (P ⫽ .02), and the ability to move the phantom (P ⫽ .01) were all associated with PLP. Odds ratio calculations strengthen these associations (Table 3). No association was found for gender (P ⫽ .70), level of amputation (P ⫽ .09), diabetes (P ⫽ .49), smoking and diabetes (P ⫽ .17), age (t ⫽ ⫺0.5, df 50, P ⫽ .96), telescoped phantom (P ⫽ .47), the ability of the phantom to move itself (P ⫽ .48), exteroceptive sensations (P ⫽ .18), and super-added sensations (P ⫽ .67). Exploratory analysis to identify why smokers and diabetics varied showed that smokers experienced pain longer than diabetics, before the amputation (P ⫽ .01).

Similarities Between Preamputation and Postamputation Pain PLP intensity was significantly lower than the preamputation pain (Current VAS, t ⫽ 5.95; df ⫽ 40, P ⫽ .0001: Worst VAS, t ⫽ 8.11; df ⫽ 47, P ⫽ .0001; Current PPI, t ⫽ 4.81; df ⫽ 40, P ⫽ .0001: Worst PPI, t ⫽ 7.35; df ⫽ 47, P ⫽ .0001). The pattern of descriptors chosen for preamputation pain and PLP is shown in Fig 2. Statistical comparison of

797 the pattern of the descriptors chosen was performed using two-way repeated-measures ANOVA. There was a significant main effect for time (F1,40 ⫽ 23.03, P ⫽ .0001), with fewer descriptors chosen postamputation. The type of descriptors chosen (F1,40 ⫽ 107.24, P ⫽ .0001) altered before to after amputation, with a higher ratio of sensory words chosen to affective words chosen for PLP. A significant interaction effect was also found (F1,40 ⫽ 7.50, P ⫽ .01). The pattern of descriptors chosen to describe the pain therefore changed from the preamputation to the postamputation period. Postamputation, very few affective words were chosen and it is this that represents the main change in the ratio of the 2 types of descriptor. Visual inspection of each pain description profile found that no individual preamputation pain was found to be identical to the description given for PLP. On average, 59% of descriptors chosen at level 2/3 (moderate/severe) for PLP were also chosen at that level for the worst preamputation pain.

Discussion Preamputation Factors Associated With PLP Coping Coping style and more specifically a predilection to passive coping is the strongest link between the preamputation condition and PLP found by the present study. Indeed preamputation catastrophizing was found to be associated with both the presence and regularity of PLP. This confirms previous findings25 but goes further by identifying that the coping style was present before the amputation and is not therefore resulting from the presence of PLP. Passive coping and catastrophizing have been found to be associated with the reporting of high pain intensity and disability in chronic pain67,71 and more recently has been identified as a predictor for disability in neck and low back pain sufferers49 and for all musculoskeletal pain.66 These studies evaluated the link between the coping styles and development of chronic pain. In the present study, the relevant question is whether the time to resolution of PLP (which was initially present in almost all patients) is influenced by a particular coping style. The close association of preamputation catastrophizing and the presence and regularity of PLP suggests that as a trait, catastrophizing has an impact on the maintenance of chronic PLP. Our results are reminiscent of a study of patients recovering from acute dental inflammation which showed poorer heat pain tolerance among catastrophizers and suggested that catastrophizing per se may prolong recovery from central sensitization.12 In the case of PLP, a well-known neuroplastic change is that of cortical reorganization,3,19,42,58 and it is tempting to suggest that this development, which is both common and reversible, is not immune to the influence of negative thought processes. It is of note that catastrophizing correlates with cerebral activities in the medial pain

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Factors Associated With Phantom Pain Development

Figure 2. Descriptors used for preamputation and postamputation pain.

system and perhaps more importantly inversely with activity in the top-down neuromodulation system.65 Future studies could focus upon the potential that the thought processes involved in coping could directly or indirectly influence the cortical reorganizations that occur in the periamputation period and that coping style modification could be a legitimate preemption target.

Pain Links were found between preamputation pain intensity (current PPI; t ⫽ 2.24, df 50, P ⫽ .03: worst PPI; t ⫽ 3.20, df 11.54, P ⫽ .01, and worst VAS: t ⫽ 2.23, df 11.29, P ⫽ .05) and the presence of PLP 6 months after the surgery. No associations could be found between any other aspect of the preamputation pain or the PLP. This suggests preemption of pain is not guaranteed to affect the levels of PLP postamputation. Preamputation pain has been considered a risk factor for PLP38 but prospective studies designed to confirm it are few and suffer from small numbers. In a prospective study with 56 patients, it was found that preamputation

pain predicted PLP at 1 and 3 months but not at 6 months.52 Their results contrast to the findings in the present study in which the association was seen at 6 months. However, their patients also took part in an epidural blockade preemption study, which may have had a bearing on the results, and PLP in their study was defined as pain ⬍20/100 on VAS, making comparison difficult. It is interesting that patients choosing the word “tender” to describe their preamputation pain were more likely to have PLP at 6 months. In our clinical experience, tender is commonly used by patients to describe evoked pain; either allodynia or generalized sensitivity to mechanical stimuli. Mechanical allodynia is frequently considered as a classic sign of central “sensitization,” that is, a functional remapping of neuronal connections, or unmasking of previously silent synapses, whether at the level of the dorsal horn, thalamus, or cortex.75 Novel brain imaging methods have shown allodynia in some conditions to be associated with significant alteration in the areas that contribute to the pain matrix,33,46 which

ORIGINAL REPORT/Richardson et al are similar to the cortical reorganizations known to be associated with PLP.3,19,42,58

Other Associations Stump pain and the ability to move the phantom were postamputation factors associated with PLP. Stump pain has previously been shown to coexist with phantom limb pain and it has been claimed that increasing local pain in the stump also increases phantom pain.7 Even if there is a significant cortical reorganization involving the leg, one would expect intact stumps to have retained their connectivity with the neuronal pool adjacent to those with representation areas for the missing limb, or possibly forming functional connections with them,50 which could be 1 reason for this finding. Movable phantoms have not been reported very often. Many upper limb phantoms are reported as fixed58 so this may suggest a difference between upper and lower limb amputation. The fact that this study assessed patients 6 months after amputation (versus years in other studies) may have a bearing on the matter. It is conceivable that in some patients the pattern will change over time. Further long-term follow-up is indicated. Telescoped phantoms were as likely to be painful as complete phantoms, corroborating the results from a previous study of 32 amputees50 adding further evidence against the maxim that telescoping reduces PLP. The association between smoking and PLP suggests that it is protective (OR ⫽ 0.19; 95% CI, 0.04 – 0.85). This is hard to rationalize given that smokers had pain longer than diabetics before the amputation (mean, 20.7 months vs 5.2 months) and the recent results which found that smokers were more likely to have more pain in more sites than nonsmokers in a general population study.32 At present, this finding remains unexplained. Overall, these results vary from those produced in a study using logistic regression.11 That was a cross-sectional study with a sample taken from a limb fitting center and so was more likely to identify postamputation rather than preamputation factors. Accounting for the fact that the present study was longitudinal and had a relatively small sample size the 2 studies should be viewed as complementary to each other.

Similarities Between Preamputation and Postamputation Pain The descriptors chosen for the pre and postamputation pains were not the same. Proportionately less affective words were chosen for PLP than for critical limb ischemia, hence at first sight this appears to suggest that the pain memory theory is wrong. However, it could be argued that as affective words describe the effect of a pain on the individual rather than the pain per se, the reduction in the affective component might be due simply to a reduction in the pain intensity. It is known that pain intensity and duration are associated with distress16 and that memories are not necessarily consistent,70 and this could reasonably suggest that the pain memory is not rejected. On balance though, it is believed that these

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results alongside those from elsewhere suggest that PLP does not match the characteristics of preamputation pain and therefore challenges if not refutes the memory theory. Ultimately, if preamputation pain is considered to be a genuine risk factor for PLP, the mechanism whereby this happens is unlikely to just be that of prolonged maintenance of the previous pain (“pain memory”). We believe that a more likely explanation is that preamputation pain has primed the afferent system throughout the neuroaxis, including the dorsal horn, thalamus and the brain’s “pain matrix” so that the altered neural activity generating the phantom is easier to initiate and sustain. It may well be that this ‘priming effect’ itself is not sufficient to maintain the abnormal neural activity but it requires constant afferent input from the representative region. The postoperative nociceptors from the stump would provide this input. Our finding of the association between stump pain and PLP supports this hypothesis, as does the general tendency of the PLP to reduce over time as the stump heals.54 In the past, super-added pains have also been used to support the pain memory theory. No such pains were identified in this group which lends more support against the memory theory however it is possible that none from this sample had significant pain in their limb previous to their PVD. Further exploration into this phenomenon is required as 15.4% did describe a “memory type” phenomenon associated with their phantom being clothed.

Clinical Utility of These Results An assessment of the strength of this evidence is limited by the relatively small sample size; however, statistically significant results from small samples have a high power. Future research will be required to replicate these results. Attempts were made to identify a preamputation assessment tool for the risk of PLP. Composite pain and coping scores were assessed; however, low numbers generally impaired the progress. It might be possible however to use a rough calculation when high preamputation pain intensity is accompanied by high passive coping and the use of the descriptor “tender.” All 3 together may be enough to suggest the high possibility that PLP will occur however this will need extensive testing.14,23

Conclusion Preamputation physical and psychological factors have been found to be associated with the development of PLP postamputation of a lower limb. Preamputation pain might play a role in PLP development, but the relationship between its intensity and duration needs further elucidation. Passive coping styles have previously been found to be prevalent in PLP sufferers. This study suggests that these were present before the amputation and may have influenced the development and maintenance of PLP hence future studies aimed at trying to preempt PLP should target coping style.

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