Biofeedback in the Treatment of Phantom Limb Pain: A Time-Series Analysis

Transcription

1 Applied Psychophysiology and Biofeedback, Vol. 30, No. 1, March 2005 ( C 2005) DOI: /s Biofeedback in the Treatment of Phantom Limb Pain: A Time-Series Analysis R. Norman Harden, 1,2 Timothy T. Houle, 1 Samara Green, 1 Thomas A. Remble, 1 Stephan R. Weinland, 1 Sean Colio, 1 Jeffrey Lauzon, 1 and Todd Kuiken 1 Phantom limb pain (PLP) is a noxious, painful sensation that is perceived to occur in an amputated limb. It has been reported to occur in up to 85% of amputees. This pilot study examined the effectiveness of biofeedback in the treatment of nine individuals with PLP who received up to seven thermal/autogenic biofeedback sessions over the course of 4 6 weeks. Pain was assessed daily using the visual analog scale (VAS), the sum of the sensory descriptors, and the sum of the affective descriptors of the McGill short form. Interrupted time-series analytical models were created for each of the participants, allowing biofeedback sessions to be modeled as discrete interventions. Analyses of the VAS revealed that a 20% pain reduction was seen in five of the nine patients in the weeks after session 4, and that at least a 30% pain reduction (range: 25 66%) was seen in six of the seven patients in the weeks following session 6. Sensory descriptors of pain decreased more than the affective pain descriptors. These preliminary results provide some support for the use of biofeedback in the treatment of PLP and indicate the need for further, definitive study. KEY WORDS: phantom limb pain; post amputee pain; thermal biofeedback; time-series analysis. INTRODUCTION Phantom limb pain (PLP) is defined as a painful sensation occurring in a missing body part (Davis, 1993a, 1993b). PLP often begins within the first week after amputation and is primarily described as knifelike, burning, squeezing, and throbbing (Davis, 1993a, 1993b). Mechanisms for PLP are not well understood, and standard treatments for pain (i.e., drugs) have proven fairly ineffective (Iacono, Sandyk, Bamford, Awerbuch, & Malone, 1987; Sherman, 1997). The reported incidence, prevalence and intensity of PLP over the past 30 years is significant. In a 1983 study, as many as 90% of amputees reported some degree of sensation associated with a phantom limb (Jensen, Krebs, Nielsen, & Rasmussen, 1983). In the past 10 years, more sharply focused studies have shown a consistent incidence of PLP in 1 Center for Pain Studies, Rehabilitation Institute of Chicago/Northwestern University Medical School, Chicago, Illinois. 2 Address all correspondence to R. Norman Harden, Center for Pain Studies, Rehabilitation Institute of Chicago, 446 Ontario Street, Suite 1011, Chicago, Illinois 60611; nharden@ric.org /05/ /0 C 2005 Springer Science+Business Media, Inc.

2 84 Harden, Houle, Green, Remble, Weinland, Colio, Lauzon, and Kuiken 50 59% of amputee patients (Davison & Jones, 1995) (Montoya et al., 1997) (Kooijman, Dijkstra, Geertzen, Elzinga, & van der Schans, 2000). In the largest study of PLP intensity to date, Kooijman, Dijkstra, Geertzen, Elzinga, and Schans (2000) evaluated the presence of pain in 124 amputees in the Netherlands. Sixty-four percent of the Netherlands sample reported experiencing at least a moderate amount of suffering from their pain, with 40% of the sample reporting that they always experienced PLP and another 20% reporting PLP a few times a day. The incidence, frequency, and degree of suffering caused by PLP underlines the importance of developing effective treatments for this condition, as well as other types of post-amputation pain. Standard Medical Treatment in Post-Amputation Pain Standard medical treatments for PLP have been relatively ineffective, and the need for better treatments has been consistently noted (Sherman, 1997). At the time of this report, no pharmacologic agent has been shown to be consistently effective in the treatment of PLP. In 1987, Iacono, Linford, Pharm, and Sandyk reviewed the literature on opioids, b-blockers, anticonvulsants, tricyclics, neuroleptic agents, and neurosurgical interventions. They concluded: Unfortunately, partial relief or failure is often the result of even the most diligent medical management (Iacono, Linford, & Sandyk, 1987). In a recent review of all English trials published between 1966 and 1999, Halbert, Crotty, and Cameron reviewed 12 trials, which included the use of epidurals, nerve blocks, calcitonin, and transcutaneous electrical nerve stimulation. The authors found only three trials that reported modest and temporary decrease of amputee pain. Two positive trials examined the treatment of acute phantom pain with preoperative ( pre-emptive ), intraoperative, and early (at <2 weeks) postoperative interventions utilizing epidural anesthesia (Nikolajsen, Ilkjaer, Christensen, Kroner, & Jensen, 1997) and a regional nerve block (Pinzur, Garla, Pluth, & Vrbos, 1996). Another positive study examined the treatment of chronic phantom pain with a late (at >2 weeks) postoperative intervention utilizing galvanic stimulation using a metal threaded sock (Farabloc Development Corp., Coquitlam, BC, Canada)(Conine, Hershler, Alexander, & Crisp, 1993). Halbert, Crotty and Cameron emphasized the importance of ongoing research to develop more effective treatments for PLP (Halbert, Crotty, & Cameron, 2002). No differences between gabapentin and placebo were observed for change in VAS ratings, mood, sleep interferences, or activities of daily living (Bone, Critchley, & Buggy, 2002). Psychophysiological Factors in Post-Amputation Pain The current lack of understanding of psychophysiological mechanisms may be the primary reason why standard treatments (i.e., medications) have been relatively ineffective, but new imaging and quantitative psychophysical techniques are beginning to elucidate the mechanisms of PLP. There is a growing body of evidence that suggests PLP is related to sympathetic nervous system activity (Katz, 1997b). Possible etiological mechanisms in PLP are related to sympathetic over-activity with primary vasoconstriction, and ischemia of pathologically altered structures in the residual limb, (such as neuroma), or direct noradrenergic stimulation of neuroma (Devor, 1997). It is possible that other pathologic tissue in the residual limb (such as pathologic receptors, or up regulation of normal receptors) may

3 Biofeedback in the Treatment of Phantom Limb Pain 85 become more sensitive to local or circulating catecholamine levels (Harden et al., 2004). Several studies suggest a complex relationship between residual limb temperature and potential PLP involvement (Sherman, Bruno, & Sherman, 1987). Katz s study of 28 amputees revealed evidence of the relationship between sympathetic arousal and pain intensity (Katz, 1997b). Further, in his review of the literature, Katz found that medications and surgeries designed to reduce or stop sympathetic activity produced significant, although temporary, reduction in pain (Katz, 1997a). Since these studies indicate that vasoconstriction and a relative decrease in temperature in the residual limb are physiologic markers of autonomic disturbance, these signs may also serve as physiologic targets for treatment. Biofeedback in the Treatment of PLP Biofeedback has become a common therapy used to successfully treat many chronic pain conditions. Such biofeedback modalities include EMG biofeedback; skin temperature feedback; and muscle relaxation procedures (Arena & Schwartz, 2003; Schwartz & Schwartz, 2003), which help reduce muscle tension and increase blood flow (which has been used for PLP) (Belleggia & Birbaumer, 2001); The use of biofeedback to treat PLP is not novel; several prior studies have yielded positive results (Belleggia & Birbaumer, 2001; Dougherty, 1980; Sherman, Gall, & Gormly, 1979). Sherman, Gall, and Gormly (1979) have reported that different descriptions (symptom sets) of PLP vary in response to different forms of biofeedback therapy. Recently, Sherman and collaborators have been attempting to match behavioral and medical treatments of PLP with underlying physiological correlates (e.g., amputees with burning pain receive thermal biofeedback; patients with cramping pain receive EMG biofeedback). Unfortunately, all but one of these studies are case reports (the exception being Sherman et al., 1979) with widely varying methods and materials. The effectiveness of specific biofeedback procedures matched by pain description (e.g., burning or cramping) in this population largely remains unproven. The present study examined the effectiveness of thermal biofeedback training in treating PLP. Thermal biofeedback may be particularly well suited to reduce some of the complex physiological factors that affect PLP by mediating net regional sympathetic arousal. Thermal biofeedback allows an individual to monitor peripheral temperature and thereby indirectly monitor and modify sympathetic activity (Freedman, 1991). If sympathetic nervous system activity is indeed causally related to PLP, gaining control over such activity should result in decreased pain. Increased control over sympathetic activity is hypothesized to lead to decreased pain in the weeks following treatment. METHOD Participants To be eligible for the study, patients had to report PLP in excess of phantom sensations (mean VAS pain at baseline = 38.2, SD = 21.4). Nine outpatients (five males, four females) being treated for PLP participated in this pilot study. Patients average age was 57.6 years (SD = 11.0). Five patients had lower extremity amputations and four had upper extremity

4 86 Harden, Houle, Green, Remble, Weinland, Colio, Lauzon, and Kuiken amputations. Four subjects had bilateral amputations; two below the knee, and two below the elbow. Six of the patients used prosthetics. All patients provided informed consent for treatment with biofeedback. All patients were instructed to maintain their current medication regimens without alteration throughout the course of the study. Thus, the study represents biofeedback as an add-on intervention to our pharmacologic standard of care. Measures and Materials Subjects completed a twice-daily pain diary. The diary consisted of the McGill Pain Questionnaire Short Form (MPQ-SF) (Melzack, 1987), the Beck Depression Inventory (BDI) (Beck, Steer, Beck, & Newman, 1993; Beck, Steer, & Brown, 1993), and the trait portion of the State-Trait Anxiety Inventory (STAI) (Spielberger, Gorsuch, & Lushene, 1970). McGill Pain Questionnaire: Short Form The complete MPQ-SF was administered at each clinic visit to assess weekly changes in overall pain intensity. Beck Depression Inventory (BDI) The BDI was used to assess depressive symptoms at baseline and at study termination. This measure was used in secondary analyses to determine whether topiramate or its pain relief improved depressive symptoms, and whether the effectiveness of topiramate is affected by the extent of depressive symptoms. Trait Form of the State-Trait Anxiety Inventory (STAI) The STAI, which assesses anxiety related symptoms, was used at baseline and study termination for secondary analyses similar to those described for the BDI. Temperature was monitored on the Thought Technology Biograph using ProComp 2.0 software. Procedure During the initial visit, subjects were informed about the study and provided consent. Patients completed a general health questionnaire and questions or issues concerning treatment were discussed. Participants were educated about the rationale of the study and no deception was used concerning the nature of the treatment. Finally, the subjects were given the pain diaries with instructions to complete the diaries at the same time each morning and each evening. There was an average time of 8.7 days between the initial visit and first biofeedback session (range 4 20 days). Biofeedback consisted of three treatment phases: treatment-training (sessions 1 3), warming (sessions 4 6), and follow-up (session 7). A script provided standard introduction

5 Biofeedback in the Treatment of Phantom Limb Pain 87 to biofeedback, rationale, and instruction on relaxation training and thermal biofeedback. It was read to each patient during visit one of session one only. During each of the first three treatment-training sessions, biofeedback sensors were attached and a 10-minute baseline was recorded. Next, a 20-minute treatment period began with the biofeedback therapist reading 20 autogenic phrases to the patient in a slow and rhythmic manner. Subjects were instructed to repeat the phrases they liked best while imagining sensations of warmth and heaviness in their unaffected extremities. During this stage, the patients received feedback from a healthy extremity. Patients were then instructed to practice the technique at home at least once a day. During treatment-training sessions 2 and 3, the patient s progress was reviewed and any questions regarding the warming techniques were discussed. Following the ten-minute baseline period, the standard 20 autogenic phrases were read to the patient at the beginning of the 20-minute treatment period as in session one, but beginning in session 2 the patient was instructed to gradually move focus from the healthy limb to the residual limb, and was given the feedback received from both a healthy digit and the residual limb. Warming sessions (4 6) included a 10-minute baseline thermal recording focused on subject feedback from the residual limb only. In these sessions, the autogenic phrases were not read, allowing the patient to self-direct warming via their newly learned individual repertoire of phrases. The patient was left alone to allow self-initiated warming techniques for 20 minutes. Following this phase, the patient was instructed to finish the technique, and any problems encountered were discussed. Session 7 was a follow-up session. Follow-up biofeedback was similar to warming sessions 4, 5 and 6, except that equivalent levels of feedback were not provided. During the final session, problems with techniques were discussed along with a therapeutic directive to foster patient s perceived ability to successfully employ the autogenic techniques learned throughout treatment (Bandura, 1977). This is equivalent to a total dose (actual time on the biofeedback equipment, receiving feedback) of 140 minutes. Biofeedback Technique Thermistors were attached to consistent multiple sites throughout the treatment. A thermistor was fixed to the end of the residual limb in an unscarred area. Under circumstances of a bilateral amputation, the primary thermistor was attached to the same specific residual limb in order to maintain consistency throughout treatment. A second thermistor was attached to the corresponding site on the contralateral limb. A final thermistor was attached to an extremity of a healthy limb. Data Analysis Descriptors of the MPQ-SF were separately summed to create a sensory and affective score for each diary entry. Morning and afternoon diary entries were averaged to create a ratings score for affective, sensory, and VAS pain. This data reduction technique was conducted to eliminate diurnal variation effects from the analysis. Missing values were replaced using adjacent point interpolation. Reported compliance with the diaries was excellent, with less than 1% of the data missing.

6 88 Harden, Houle, Green, Remble, Weinland, Colio, Lauzon, and Kuiken Analyses were carried out using the SPSS 11.5 for Windows package (SPSS Inc., Chicago, IL). To identify the comparative effects of biofeedback treatment over time, the VAS, sensory, and affective scores of the participant s daily diary were modeled using a time-series regression analysis. Psychometric data collected at each session were analyzed using a repeated measures analysis of variance. For each subject, unique interrupted time-series regression models were used to model pain reporting over time. A separate model was created for affective, sensory, and VAS pain scales. Treatment was divided into discrete time periods beginning on the day of the biofeedback session and including all of the days prior to the next session. Thus, each patient s treatment was divided into sections (treatment periods) corresponding to the biofeedback sessions. Treatment periods were modeled as discrete interventions and were dummy coded to represent abrupt, permanent impacts on pain reporting. The dummy vectors for each treatment period were coded such that they contained a 1 for observations corresponding to that treatment period and a 0 for all else. Each of the regression weights then corresponded to changes in pain from baseline associated with that treatment period. Use of the dummy vectors allowed for statistical evaluation of intra-individual changes in pain biofeedback session. When observations are collected repeatedly over time, subsequent observations tend to be more related than observations more temporally distant. This process has been called autocorrelation, and is the correlation of the series with itself. Autocorrelation in a series can lead to the violation of statistical assumptions. To ensure the validity of the inferential statistics, a first-order autoregressive error process was included to correct for autocorrelation in the residuals (Box, Jenkins, & Reinsel, 1994). To ensure that the residuals were white noise (were not correlated with time; a necessary assumption in regression analysis), the corrected models, also including the session parameters, were then evaluated using the modified Box-Pierce Q. In all models, a first-order autoregressive parameter successfully reduced the residuals of the model to white noise, and thus the significance values of the models can be interpreted conventionally. Finally, mixed models were used to aggregate the individual parameters of the timeseries regression models for global comparisons by treatment session. The use of these models allowed for modeling the group s changes throughout treatment. In addition, each participant s individual error structure for specification was uniquely modeled (i.e. the temporal relationship between treatment periods). RESULTS Table I presents the baseline pain values of each subject along with the percentage change in pain corresponding with each treatment period on the individual level. Eight out of nine patients in the study showed statistically significant improvement after some biofeedback sessions, and overall improvement increased as treatments increased. Four out of nine patients displayed statistically significant changes in pain at some point during treatment (p <.05). After session 4, five out of nine patients reported experiencing at least a 20% reduction in pain, and by session 6, the 7 patients still enrolled reported an average of 39.3% reduction in pain (range 25 66% reduction). One patient (#2) reported statistically significant increases in pain in several treatment periods (p <.05; see Table I).

7 Biofeedback in the Treatment of Phantom Limb Pain 89 Table I. VAS Pain Score at Baseline with Percentage Change for Each Subject by Treatment Period Session Subject BL B B Note. B patient had substantial hot-burning pain at baseline; BL = baseline. p<.05 decrease in pain. p<.01 decrease in pain. p<.001 decrease in pain. p<.05 increase in pain. Figure 1 displays the aggregated mean and median reduction in VAS pain as a function of treatment period. The median pain response was quite similar to the mean response, indicating that the observed treatment effects were not largely influenced by extreme outliers (see Table I for individual responses). Beginning after the fourth treatment session (p =.06) and continuing through the remainder of treatment, statistically significant decreases in pain as compared with baseline were observed (p s <.01). Further, the effects due to treatment increased with subsequent sessions as after sessions 5 7, patients reported less pain than after sessions 1 3 (p <.01). (See Fig. 1). The subject sample reported low levels of anxiety and depressive symptoms even at baseline (STAI: M = 34.4, SD = 11.6; BDI: M = 8.75, SD = 7.1). Although slight decreases were seen in both the STAI and BDI over treatment, observed changes were not statistically significant (Time: p s >.25). Figure 2 displays the aggregated mean and median reduction in MPQ-Sensory pain as a function of treatment period. Beginning after the third treatment session (p =.051) and continuing through the remainder of treatment, statistically significant decreases in sensory pain as compared with baseline were observed (p s <.05). The median pain response was quite similar to the mean response, indicating that the observed treatment effects were not largely influenced by extreme outliers. Fig. 1. Average percentage change in VAS by treatment week, p.01.

8 90 Harden, Houle, Green, Remble, Weinland, Colio, Lauzon, and Kuiken Fig. 2. Average percentage change in MPQ-sensory by treatment week, p.05. Figure 3 displays the aggregated mean and median reduction in MPQ-Affective pain as a function of treatment period. Affective pain did not decrease throughout treatment as no significant differences were observed between any treatment periods (p >.05). The mean pain response differed considerably from the median response, reflecting both the variation in response to treatment and the low amount of observed variance in this measure. Pain, as measured by the VAS, decreased throughout treatment. The nine patient mean VAS score at baseline was M = 38.2 (SD = 21.4). Average pain decreased during most treatment periods and was M = 37.8 (SD = 23.4) for period 1, M = 34.3 (SD = 18.6) for period 2, M = 37.3 (SD = 23.5) for period 3, M = 32.9 (SD = 22.9) for period 4, M = 28.2 (SD = 20.3) for period 5, M = 20.5 (SD = 18.1) for period 6, and M = 16.8 (SD = 6.3) for period 7. Previous research has suggested a superior response to biofeedback in those amputees with burning pain (Sherman, Gall, & Gormly, 1979), but thermal biofeedback did not appear to decrease pain in amputees with burning pain in this study. The baseline diaries of subject #3 and subject #8 identified them as subjects with a predominantly hot-burning presentation, so those subjects are noted with a B in Table I. These two subjects reported comparatively more burning pain than the other subjects in the analysis and also reported more burning quality to their pain in conjunction with the other sensory descriptors of the MPQ (although all subjects reported experiencing more than one type of sensory quality to their pain). As can be seen in Table I, subject #3 was one of the better responders to the biofeedback, but interestingly, subject #8, who reported the highest amount of Fig. 3. Average percentage change in MPQ-affective by treatment week.

9 Biofeedback in the Treatment of Phantom Limb Pain 91 hot-burning sensations, reported less benefit than the average participant in the study. The small subsample precludes meaningful group comparisons, but this study did not show a superior response from these two participants. DISCUSSION This pilot study supports the hypothesis that thermal biofeedback training may have an important role to play in the management of PLP. After receiving six sessions of training (and a dose of 140 minutes of biofeedback), patients reported an average of 39% decrease in daily pain, with three patients reporting a greater than 50% reduction. Changes in the sensory descriptors of pain (i.e. sharp, burning etc.) were mirrored by changes in the VAS. The treatment appeared to be broadly effective in this small sample, with only one patient reporting a significant increase in pain. Furthermore, it appears that all the subjects that responded had not plateaued, and it is likely that more treatment (a higher dose ) may well lead to greater improvement. This pilot study was not designed or powered to investigate PLP mechanisms, but there are multiple possible explanations for these results. For instance, the results of this study may indicate that patients were able to (centrally) alter the perceived painful sensations in their residual or phantom limbs, or it may be indicative of physiologic change in the periphery, such as improved blood flow and/or decreased sympathetic output. It is very likely that the impact is situated at multiple levels of the neuro-axis; afferent (sensory processing), efferent (autonomic) and central. Another logical explanation for the observed decrease in pain, and one that has received a great deal of attention in the headache literature, is through a possible mechanism for induced cognitive changes. Biofeedback facilitates cognitive changes in patients by demonstrating that physiological processes are under their control (i.e. increased internal control) and that they are in fact able to influence these physiological processes (i.e. enhancing self-efficacy) (Rokicki et al., 1997). Thus, biofeedback may simply be a vehicle to shift a patient s focus from external to internal methods of pain coping, making perceived pain more tolerable. Future studies should assess changes in perceived control and self efficacy in the treatment of PLP, with similar statistical methods used in the present study to identify if cognitive changes predict decreases in pain. Future studies could monitor, record and correlate the changing physiological states induced by biofeedback (i.e. ability to control hand temperature) with time-series regression methodology. This would identify whether changes in physiology predict or predate decreases in pain and sympathetic arousal. In this pilot the therapist reported (anecdotally) that all subjects achieved a degree of control over the physiologic variable of interest (temperature of the residual limb), this is a critical variable that must be formally monitored and recorded in future, definitive studies. We can and should utilize more sophisticated psychophysical and psychometric methodologies. The results from the McGill short form pain questionnaire indicated that affective descriptors of pain did not decrease as much as sensory descriptors. This is likely a floor effect, since the nine patients in this study all initially reported low levels of affective pain (M = 1.8 out of a possible score of 12) which did not fluctuate greatly during the course of treatment. Changes that occurred during this study in the affective descriptors of pain were neither trending nor significant, and did not contain a great deal of daily variance. This

10 92 Harden, Houle, Green, Remble, Weinland, Colio, Lauzon, and Kuiken information may reveal a particular bias about this small sample: the patients participating in treatment did not appear to have a large emotional component to their pain experience (i.e. describing the pain as punishing-cruel ), and they reported low levels of depressive and anxiety symptoms, even at baseline. Thus, the relative lack of changes in affective pain reporting must be interpreted with an eye toward the small sample size and makeup of this particular group. The sample size of this pilot limits the generalizability of the results. The use of timeseries analysis and hierarchical linear modeling provided robust statistical power which allowed statistical differences to be detected with only nine participants, but the stability of the results cannot be ascertained from a sample this small even though the observed effect sizes were quite large. Further study with larger samples is clearly warranted to elucidate which factors affect the treatment outcome. It will also be important to asses the durability of any positive change. The current study adds to the body of literature suggesting that thermal biofeedback may be a viable treatment option for patients with PLP. The change processes induced with biofeedback need further study, including direct comparisons with other cognitivebehavioral approaches, like relaxation training. A definitive study designed to answer some of these outstanding questions should include more objective measures of physiologic change, as correlated with the psychometrics. REFERENCES Arena, J. G., & Schwartz, M. S. (2003). Psychophysiological assessment and biofeedback baselines: A primer. In M. S. Schwartz & F. Andrasik (Eds.), Biofeedback: A practitioner s guide (3rd ed., pp ). New York: Guilford. Bandura, A. (1977). Self-efficacy: Toward a unifying theory of behavioral change. Psychological Review, 84(2), Beck, A. T., Steer, R. A., Beck, J. S., & Newman, C. F. (1993). Hopelessness, depression, suicidal ideation, and clinical diagnosis of depression. Suicide Life Threat Behavior, 23(2), Beck, A. T., Steer, R. A., & Brown, G. (1993). Dysfunctional attitudes and suicidal ideation in psychiatric outpatients. Suicide Life Threat Behavior, 23(1), Belleggia, G., & Birbaumer, N. (2001). Treatment of phantom limb pain with combined EMG and thermal biofeedback: A case report. Applied Psychophysiology and Biofeedback, 26(2), Bone, M., Critchley, P., & Buggy, D. J. (2002). Gabapentin in postamputation phantom limb pain: A randomized, double-blind, placebo-controlled, cross-over study. Regional Anesthesia and Pain Medicine, 27(5), Box, G., Jenkins, G., & Reinsel, G. (1994). Time series analysis, forecasting and control (3rd ed.). San Francisco: Holden-Day. Conine, T.,Hershler, C., Alexander, S., & Crisp, R. (1993). The efficacy of Farabloc in the treatment of phantom limb pain. Canadian Journal of Rehabilitation, 6, Davis, R. W. (1993a). Phantom sensation, phantom pain, and stump pain. Archives of Physical Medicine and Rehabilitation, 74(1), Davis, R. W. (1993b). Successful treatment for phantom pain. Orthopedics, 16(6), Davison, M., & Jones, B. (1995). A quantitative analysis of extreme choice. Journal of Experimental Analysis of Behavior, 64, Devor, M. (1997). Phantom pain as an expression of referred and neuropathic pain. In R. Sherman (Ed.), Phantom pain (pp ). New York: Plenum. Dougherty, J. (1980). Relief of phantom limb pain after EMG biofeedback-assisted relaxation: A case report. Behaviour Research and Therapy, 18(4), Freedman, R. R. (1991). Physiological mechanisms of temperature biofeedback. Biofeedback and Self Regulation, 16(2), Halbert, J., Crotty, M., & Cameron, I. D. (2002). Evidence for the optimal management of acute and chronic phantom pain: A systematic review. Clinical Journal of Pain, 18(2),

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