ADVANCES IN TREATMENT OF POST-AMPUTATION PHANTOM LIMB PAIN
Wise Young, PhD MD
W. M. Keck Center for Collaborative Neuroscience
Rutgers, State University of New Jersey, Piscataway, NJ 08854-8082
Email: wisey@pipeline.com, Date written: 27 October 2009

A CareCure member who is a recent amputee asked in a private message what treatments are available for post-amputation pain. There is currently no approved therapy acknowledged to be effective for phantom limb pain [1]. There have been many attempts at treatments with some reports of possible success. I searched the published literature of the past 12 months to see if there is anything new and here is a summary of my search.

Spontaneous recovery from phantom limb and stump pain. Most people assume that phantom limb pain is stable. Schley, et al. [2] reported that 45% of people developed phantom limb pain after amputation, 54% had phantom limb sensation, 62% had stump pain, and 79% had stump sensations. Phantom limb pain declined in 14 of 29 (48%) amputees that had such pain, was stable in 38%, and got worse in 7%. Stump pain decreased in 48% but was stable in 30%.

Phantom limb exercise has been reported to reduce post-amputation pain. This includes use of visualization procedures to “exercise” the phantom limb. Ulger, et al. [3] compared the visual analog score for pain in two groups of 10 patients. One group (control) received standard prosthetic training and general exercise. The other group (treated) received phantom limb exercises and prosthetic training. At the end of 4 weeks, the treated group had significantly reduced visual analog scores.

Mirror therapy has been suggested to have beneficial effects on phantom limb pain. Ezendam, et al. [4] systematically reviewed fifteen papers reporting mirror therapy to treat upper limb function and concluded that most of the studies were weak methodologically and that the results suggest possible benefit in patients after stroke and complex regional pain syndrome (CRPS) but the effectiveness in other patient groups such as post-amputation phantom limb pain has yet to be determined. Mercier & Sirigu [5] found that patients undergoing mirror therapy reported an average of 38% decrease in background pain on visual analog scales with 5 of 8 patients reporting >30% reduction of pain. Darnall, et al. [6] described a home-based mirror therapy program for lower limb phantom pain.

Local anesthesia of mirrored sites on the intact leg has been used to treat phantom limb pain. Casale, et al. [7] did a placebo controlled trial injecting local anesthesia into mirror pain sites in the intact limb. They studied 8 amputees who have had phantom limb pain for at least 6 months. Each patient received either bupivacaine (a long acting local anesthetic) or saline into areas of the leg mirroring the phantom pain in the missing leg. After 72 hours, they injected again. At 60 minutes after injection, patients injected with local anesthesia had significantly reduction of phantom limb pain.

Lesions of the dorsal root entry zone (DREZ) have long been used to treat brachial plexus avulsions with some success but have not been used as often to treat phantom limb sensations after arm amputation. Zheng, et al. [8] did DREZ in 14 patients who had both traumatic brachial plexus avulsions and upper limb post-amputation phantom limb pain. Nine of 14 (64%) of patients had satisfactory pain relief. Six had some alteration of the phantom limb pain while 5 patients had little or no relief of pain.

Motor cortex stimulation may also have some beneficial effects on phantom limb pain. Lefaucheur, et al. [9] did motor cortex stimulation to treat refractory neuropathic pain. They transplanted cortical stimulators into 16 patients who had various types of neuropathic pain. They then randomized the patients to stimulus “on” or “not on” and did a crossover at 1 and 3 months. In the crossover trial of 13 patients, the mean rate of individual pain relief was 48% (range 0-95%) and 60% of the patients reported good or satisfactory relief of pain.

Spinal cord stimulation has been reported to reduce critical limb ischemia and neuropathic pain. Klomp, et al. [10] reviewed five randomized trials involving 332 patients and concluded that meta-analysis of the data does not provide sufficient evidence to indicate a favorable treatment effect in any group. Jang, et al. [11] analyzed the reasons for failure of spinal cord stimulation to reduce pain, concluding that spinal cord stimulation is lesss effective for neuropathic pain of spinal cord lesions, postherpetic neuropathy, or post-amputation state; furthermore the spinal cord stimulation may aggravate allodynia.

Pulsed radiofrequency stimulation. Wilkes, et al. [12] reported a case of a patient at 3 years after amputation. She had severe phantom limb pain due to progressive peripheral vascular disease. They initially did regional local anesthetic blocks of femoral and sciatic nerve that provided temporary pain relief, They then used pulsed radiofrequency treatment with 2 cycles of 120 second at 42 degrees, pulse rate of 2 Hz, and pulse duration of 20 milliseconds. This treatment apparently resulted in long-term relief of the phantom limb pain and the patient weaned herself off all oral medication and was pain-free for 4 months at the time of the report. Ramanavarapu & Simonpoulos [13] has reported that treatment of the L4/L5 nerve root may reduce intractable stump pain.

Drug therapies that are typically used include antidepressants, anti-convulsants, and opioids [14]. Su, et al. [15] reported that midazolam is effective in reducing severe phantom limb pain in a patient, aggravated by spinal anesthesia. Hawamdeh, et al. [16] in Jordan reported that patients with amputations have a 37% and 20% prevalence of anxiety and depressive symptoms but the presence of pain is not related to pain. Chazan, et al. [17] reported the use of ketamine in opioid tolerant patients, concluding that it is an efficient adjuvant analgesic for intractable severe pain.

References
1. Zanni GR and Wick JY (2008). Understanding amputation. Consult Pharm 23: 944-8, 953-4. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Approximately 134,000 amputations occur annually in the United States, resulting mostly from peripheral vascular disease. The risk of amputation increases with age, peaking among those 85 years of age and older. As a lifesaving and life-defining procedure, amputations result in physical and emotional changes affecting quality of life. Phantom pain is problematic for many patients, and agents approved by the Food and Drug Administration for phantom pain are nonexistent. Pharmacists should be knowledgeable about weight-based dosing as well as patient education guidelines.

2. Schley MT, Wilms P, Toepfner S, Schaller HP, Schmelz M, Konrad CJ and Birbaumer N (2008). Painful and nonpainful phantom and stump sensations in acute traumatic amputees. J Trauma 65: 858-64. Department of Anesthesiology and Intensive Care, University of Heidelberg, Mannheim, Germany. marcus.schley@medma.uni-heidelberg.de. BACKGROUND: The formation, prevalence, intensity, course, and predisposing factors of phantom limb pain were investigated to determine possible mechanisms of the origin of phantom limb pain in traumatic upper limb amputees. METHODS: Ninety-six upper limb amputees participated in the study. A questionnaire assessed the following question: side, date, extension, and cause of amputation; preamputation pain; and presence or absence of phantom pain, phantom and stump sensations or stump pain or both. RESULTS: The response rate was 84%. Sixty-five (81%) participants returned the questionnaire. In 64 (98.5%) participants a traumatic injury led to amputation; the amputation was necessary because of infection in one patient (1.5%). The median follow-up time (from amputation to evaluation) was 3.2 years (range, 0.9-3.8 years) The prevalence of phantom pain was 44.6%, phantom sensation 53.8%, stump pain 61.5%, and stump sensation 78.5%. After its first appearance, phantom pain had a decreasing course in 14 (48.2%) of 29 amputees, was stable in 11 (37.9%) amputees, and worsened in 2 (6.9%) of 29 amputees. Stump pain had a decreasing course in 19 (47.5%) of 40 amputees but was stable in 12 (30%) amputees. Phantom pain occurred immediately after amputation in 8 (28%) of 29 amputees between 1 month and 12 months in 3 (10%) amputees and after 12 or more months in 12 (41%) amputees. CONCLUSION: Stump pain and stump sensation predominate traumatic amputees' somatosensory experience immediately after amputation; phantom pain and phantom sensations are often long-term consequences of amputation. Amputees experience phantom sensations and phantom pain within 1 month after amputation, a second peak occurs 12 months after amputation. Revised diagnostic criteria for phantom pain are proposed on the basis of these data.

3. Ulger O, Topuz S, Bayramlar K, Sener G and Erbahceci F (2009). Effectiveness of phantom exercises for phantom limb pain: a pilot study. J Rehabil Med 41: 582-4. Department of Physical Therapy and Rehabilitation, Faculty of Health Sciences, Unit of Prosthetics and Biomechanics, Hacettepe University, Samanpazari, Ankara, Turkey. OBJECTIVE: To investigate the effects of phantom limb exercises on phantom limb pain. METHODS: A total of 20 traumatic amputees participated in the study. Ten received phantom exercises and prosthetic training, and 10 were treated with routine prosthetic training and a general exercise programme. Intensity of pain was evaluated using a 10-cm visual analogue scale before therapy and after 4 weeks of therapy. RESULTS: Baseline scores on the visual analogue scale were similar between the groups. Pain intensity decreased in all subjects after 4 weeks of treatment in both groups. According to the visual analogue scale scores at the end of 4 weeks, the phantom exercises group differed significantly from the general exercise group (p < 0.05). CONCLUSION: Phantom exercises appear to be effective in reducing phantom pain, but further research is required to confirm this.The results of this study indicate that phantom exercises can be used safely to alleviate phantom limb pain in lower and upper limb amputees.

4. Ezendam D, Bongers RM and Jannink MJ (2009). Systematic review of the effectiveness of mirror therapy in upper extremity function. Disabil Rehabil 1-15. Center for Human Movement Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Purpose. This review gives an overview of the current state of research regarding the effectiveness of mirror therapy in upper extremity function. Method. A systematic literature search was performed to identify studies concerning mirror therapy in upper extremity. The included journal articles were reviewed according to a structured diagram and the methodological quality was assessed. Results. Fifteen studies were identified and reviewed. Five different patient categories were studied: two studies focussed on mirror therapy after an amputation of the upper limb, five studies focussed on mirror therapy after stroke, five studies focussed on mirror therapy with complex regional pain syndrome type 1 (CRPS1) patients, one study on mirror therapy with complex regional pain syndrome type 2 (CRPS2) and two studies focussed on mirror therapy after hand surgery other than amputation. Conclusions. Most of the evidence for mirror therapy is from studies with weak methodological quality. The present review showed a trend that mirror therapy is effective in upper limb treatment of stroke patients and patients with CRPS, whereas the effectiveness in other patient groups has yet to be determined.

5. Mercier C and Sirigu A (2009). Training with virtual visual feedback to alleviate phantom limb pain. Neurorehabil Neural Repair 23: 587-94. Center for Cognitive Neuroscience, Bron, France. catherine.mercier@rea.ulaval.ca. BACKGROUND: Performing phantom movements with visual virtual feedback, or mirror therapy, is a promising treatment avenue to alleviate phantom limb pain. However the effectiveness of this approach appears to vary from one patient to another. OBJECTIVE: To assess the individual response to training with visual virtual feedback and to explore factors influencing the response to that approach. METHODS: Eight male participants with phantom limb pain (PLP) resulting from either a traumatic upper limb amputation or a brachial plexus avulsion participated in this single case multiple baseline study. Training was performed 2 times per week for 8 weeks where a virtual image of a missing limb performing different movements was presented and the participant was asked to follow the movements with his phantom limb. RESULTS: Patients reported an average 38% decrease in background pain on a visual analog scale (VAS), with 5 patients out of 8 reporting a reduction greater than 30%. This decrease in pain was maintained at 4 weeks postintervention in 4 of the 5 participants. No significant relationship was found between the long-term pain relief and the duration of the deafferentation or with the immediate pain relief during exposure to the feedback. CONCLUSIONS: These results support the use of training with virtual feedback to alleviate phantom limb pain. Our observations suggest that between-participant differences in the effectiveness of the treatment might be related more to a difference in the susceptibility to the virtual visual feedback, than to factors related to the lesion, such as the duration of the deafferentation.

6. Darnall BD (2009). Self-delivered home-based mirror therapy for lower limb phantom pain. Am J Phys Med Rehabil 88: 78-81. Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA. Home-based patient-delivered mirror therapy is a promising approach in the treatment of phantom limb pain. Previous studies and case reports of mirror therapy have used a therapist-guided, structured protocol of exercises. No case report has described treatment for either upper or lower limb phantom pain by using home-based patient-delivered mirror therapy. The success of this case demonstrates that home-based patient-delivered mirror therapy may be an efficacious, low-cost treatment option that would eliminate many traditional barriers to care.

7. Casale R, Ceccherelli F, Labeeb AA and Biella GE (2009). Phantom limb pain relief by contralateral myofascial injection with local anaesthetic in a placebo-controlled study: preliminary results. J Rehabil Med 41: 418-22. Department of Clinical Neurophysiology & Pain Rehabilitation Unit, Salvatore Maugeri Foundation - IRCCS, Scientific Institute of Montescano, Via per Montescano, 32. roberto.casale@fsm.it. OBJECTIVE: To ascertain the existence of contralateral painful muscle areas mirroring phantom pain and to evaluate the short-term effects of anaesthetic vs saline, injected contra notlaterally to control phantom and phantom limb pain. DESIGN: Double-blinded cross-over study. SETTING: Inpatients; rehabilitation institute. PARTICIPANTS: Eight lower limb amputees with phantom limb pain in the past 6 months. INTERVENTIONS: Either 1 ml of 0.25% bupivacaine or 0.9% saline injected alternately in each point with a 28-gauge needle, with 72 h between injections. Main outcome measurePhantom sensation modification and the intensity of phantom limb pain (visual analogue scale) before and after injections. RESULTS: Although present, painful muscle areas in the healthy limb do not mirror the topographical distribution of phantom limb pain. Sixty minutes after the injection, a statistically significant greater relief of phantom limb pain was observed after using local anaesthetic than when using saline injection (p = 0.003). Bupivacaine consistently reduced/abolished the phantom sensation in 6 out of 8 patients. These effects on phantom sensation were not observed after saline injections. CONCLUSION: Contralateral injections of 1 ml 0.25% bupivacaine in myofascial hyperalgesic areas attenuated phantom limb pain and affected phantom limb sensation. The clinical importance of this treatment method requires further investigation.

8. Zheng Z, Hu Y, Tao W, Zhang X and Li Y (2009). Dorsal root entry zone lesions for phantom limb pain with brachial plexus avulsion: a study of pain and phantom limb sensation. Stereotact Funct Neurosurg 87: 249-55. Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China. BACKGROUND: Lesions in the dorsal root entry zone (DREZ) have been shown to be significantly effective in relieving the pain of brachial plexus avulsion (BPA), but they have a limited effect on phantom limb pain (PLP). There is still the question remaining of whether DREZ lesions are effective in treating PLP in cases of BPA. METHODS: Our study includes 14 post-traumatic patients with BPA and upper limb amputation. All developed PLP and underwent DREZ lesions. After the surgery, patients were asked to estimate the global percent of pain relief (0-100%). The phantom limb sensation (PLS) was also inquired after. RESULTS: Overall, 9 (64.3%) of 14 patients had satisfactory pain relief; the mean follow-up was 15.2 +/- 6.6 months. Among the 9 patients with satisfactory pain relief, PLS had altered in 6 (66.7%), while, in the other 5 patients with poor pain relief, none had experienced alterations in PLS. CONCLUSION: DREZ lesions are effective in the treatment of PLP with BPA. Alteration in PLS after the surgery may be a predictive factor for good pain relief. The good response of PLP patients with BPA to DREZ lesions suggests that an evaluation of the cervical dorsal roots should be conducted in patients with post-traumatic PLP.

9. Lefaucheur JP, Drouot X, Cunin P, Bruckert R, Lepetit H, Creange A, Wolkenstein P, Maison P, Keravel Y and Nguyen JP (2009). Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain. Brain 132: 1463-71. Service Physiologie, Explorations Fonctionnelles, Hopital Henri Mondor, 51 avenue de Lattre de Tassigny, Creteil Cedex, France. jean-pascal.lefaucheur@hmn.ap-hop-paris.fr. Epidural motor cortex stimulation (MCS) has been proposed as a treatment for chronic, drug-resistant neuropathic pain of various origins. Regarding pain syndromes due to peripheral nerve lesion, only case series have previously been reported. We present the results of the first randomized controlled trial using chronic MCS in this indication. Sixteen patients were included with pain origin as follows: trigeminal neuralgia (n = 4), brachial plexus lesion (n = 4), neurofibromatosis type-1 (n = 3), upper limb amputation (n = 2), herpes zoster ophthalmicus (n = 1), atypical orofacial pain secondary to dental extraction (n = 1) and traumatic nerve trunk transection in a lower limb (n = 1). A quadripolar lead was implanted, under radiological and electrophysiological guidance, for epidural cortical stimulation. A randomized crossover trial was performed between 1 and 3 months postoperative, during which the stimulator was alternatively switched 'on' and 'off' for 1 month, followed by an open phase during which the stimulator was switched 'on' in all patients. Clinical assessment was performed up to 1 year after implantation and was based on the following evaluations: visual analogue scale (VAS), brief pain inventory, McGill Pain questionnaire, sickness impact profile and medication quantification scale. The crossover trial included 13 patients and showed a reduction of the McGill Pain questionnaire-pain rating index (P = 0.0166, Wilcoxon test) and McGill Pain questionnaire sensory subscore (P = 0.01) when the stimulator was switched 'on' compared to the 'off-stimulation' condition. However, these differences did not persist after adjustment for multiple comparisons. In the 12 patients who completed the open study, the VAS and sickness impact profile scores varied significantly in the follow-up and were reduced at 9-12 months postoperative, compared to the preoperative baseline. At final examination, the mean rate of pain relief on VAS scores was 48% (individual results ranging from 0% to 95%) and MCS efficacy was considered as good or satisfactory in 60% of the patients. Pain relief after 1 year tended to correlate with pain scores at 1 month postoperative, but not with age, pain duration or location, preoperative pain scores or sensory-motor status. Although the results of the crossover trial were slightly negative, which may have been due to carry-over effects from the operative and immediate postoperative phases, observations made during the open trial were in favour of a real efficacy of MCS in peripheral neuropathic pain. Analgesic effects were obtained on the sensory-discriminative rather than on the affective aspect of pain. These results suggest that the indication of MCS might be extended to various types of refractory, chronic peripheral pain beyond trigeminal neuropathic pain.

10. Klomp HM, Steyerberg EW, Habbema JD and van Urk H (2009). What is the evidence on efficacy of spinal cord stimulation in (subgroups of) patients with critical limb ischemia? Ann Vasc Surg 23: 355-63. Department of General Surgery, Vascular Unit, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands. h.klomp@nki.nl. The use of spinal cord stimulation (SCS) has been advocated for the management of ischemic pain and the prevention of amputations in patients with inoperable critical limb ischemia (CLI), although data on benefit are conflicting. Several reports described apparently differential treatment effects in subgroups. The purpose of this study was to analyze the data on the efficacy of SCS and to clarify preselection issues. Five randomized trials have been performed with a total number of 332 patients. Primary outcome measures were mortality and limb survival. In the largest multicenter randomized trial (n = 120), which compared SCS treatment and best medical treatment alone in patients with inoperable CLI, we determined the incidence of amputation and its relation to various predefined risk factors. We used Kaplan-Meier and Cox regression analyses to quantify prognostic effects and differential treatment effects. Meta-analysis yielded a relative risk for amputation of 0.79 and a risk difference of -0.07 (p = 0.15). The risk factor analysis clearly showed that patients with ischemic skin lesions (ulcerations or gangrene) had a worse prognosis (i.e., higher risk of amputation) (relative risk 2.30, p = 0.01). We did not observe significant interactions between this prognostic factor (or any other) and the effect of SCS. The analysis did not indicate a subgroup of patients who might specifically be helped by SCS. Meta-analysis including all randomized data shows insufficient evidence for higher efficacy of SCS treatment compared with best medical treatment alone. Although some factors provide prognostic information as to the risk of amputation in patients with CLI, there are no data supporting a more favorable treatment effect in any group.

11. Jang HD, Kim MS, Chang CH, Kim SW, Kim OL and Kim SH (2008). Analysis of failed spinal cord stimulation trials in the treatment of intractable chronic pain. J Korean Neurosurg Soc 43: 85-9. Department of Neurosurgery, College of Medicine, Yeungnam University, Daegu, Korea. OBJECTIVE: The purpose of this study is to identify the factors affecting the failure of trials (<50% pain reduction in pain for trial period) to improve success rate of spinal cord stimulation (SCS) trial. METHODS: A retrospective review of the failed trials (44 patients, 36.1%) among the patients (n=122) who underwent SCS trial between January 1990 and December 1998 was conducted. We reviewed the causes of failed trial stimulation, age, sex, etiology of pain, type of electrode, and third party support. RESULTS: Of the 44 patients, 65.9% showed unacceptable pain relief in spite of sufficient paresthesia on the pain area with trial stimulation. Four of six patients felt insufficient paresthesia with stimulation had the lesions of the spinal cord. Seventy five percent of the patients experienced unpleasant or painful sensation during stimulation had allodynia dominant pain. Third-party involvement, sex, age and electrode type had no influence on the outcome. CONCLUSION: We conclude that SCS trial is less effective for patients with neuropathic pain of cord lesions, postherpetic neuropathy or post-amputation state. Further, patients with allodynia dominant pain can feel unpleasant or painful during trial stimulation.

12. Wilkes D, Ganceres N, Solanki D and Hayes M (2008). Pulsed radiofrequency treatment of lower extremity phantom limb pain. Clin J Pain 24: 736-9. Department of Anesthesiology and Pain Management, University of Texas Medical Branch, Galveston, TX 77555, USA. dwilkes@utmb.edu. BACKGROUND: Phantom limb pain can be challenging to treat. We present a patient who developed severe phantom limb pain after revision of her lower extremity amputation due to the continued progression of peripheral vascular disease. Multiple treatment modalities had been tried without success. Pulsed radiofrequency has been successfully used to manage a number of pain syndromes. OBJECTIVE: The present case report describes the use of pulsed radiofrequency treatment for phantom limb pain. METHODS: The authors initially preformed regional blocks of femoral and sciatic nerve with 0.375% bupivicaine 15 cc and 50 microg clonidine to control the patient's pain. The blocks provided good pain relief but with limited duration. Based on reports of prolonged pain relief provided by pulsed radiofrequency treatment for other chronic pain conditions such as lumbrosacral spondylosis, we decided to apply this treatment to the patient's sciatic nerve. The patient underwent pulsed radiofrequency treatment with 2 cycles of 120 seconds at 42 degrees, pulse rate of 2 pulse/second, and pulse duration of 20 milliseconds. RESULTS: Our report shows that the sciatic nerve block with bupivicaine and clonidine, initiated approximately 3 years after amputation, produced modest short-term relief. The pulsed radiofrequency treatment resulted in long-term relief of phantom limb pain. The patient was able to wean herself off all oral medications and has been pain free for 4 months.

13. Ramanavarapu V and Simopoulos TT (2008). Pulsed radiofrequency of lumbar dorsal root ganglia for chronic post-amputation stump pain. Pain Physician 11: 561-6. Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. BACKGROUND: Chronic pain following limb amputations is now a recognized chronic pain syndrome usually described in a combination of phantom and stump pain. Both stump and phantom pain continue to be significant treatment challenges. If pharmacotherapy does not provide effective analgesia for stump pain, a clinician has interventional options that frequently give only transient benefit, or have a high chance of failure in the long run. METHODS: We selected 2 patients with primarily stump pain and difficulty tolerating the limb prosthesis. After a positive response to segmental nerve root blocks at L4 and L5, pulsed radiofrequency (PRF) was performed to the dorsal root ganglia (DRG). RESULTS: Both patients experienced 50% pain relief or better for 6 months. Each patient tolerated the prosthetic limb and could function at a higher level. CONCLUSION: PRF treatment of the DRG at the L4 and L5 nerve root level may be a therapeutic option for patients with peripherally mediated intractable stump pain. A decrease in pain intensity and improved toleration of the limb prosthesis was appreciated in both patients.

14. Schwarzer A, Zenz M and Maier C (2009). [Therapy of phantom limb pain]. Anasthesiol Intensivmed Notfallmed Schmerzther 44: 174-80. About 80 % of all extremity amputations suffer from phantom limb pain following the operation. In this context, it is important to differentiate between painful phantom limb sensations, non-painful phantom limb sensations and residual limb pain. The pathophysiology of phantom limb pain is not fully understood. Current research findings ascribe a major pathophysiological role to cortical changes as well as a disturbed body perception. Peripheral and spinal mechanisms appear less relevant in the development of phantom limb pain. An essential part of the therapy is the pharmacological treatment with antidepressants, anticonvulsives and opioids. Another significant aspect of therapy is senso-motory training, important to mention here would be mirror therapy, lateralisation and motor imaging. In case of an elective amputation, an epidural or axiliar plexus catheter should be considered prior to the amputation. The perioperative treatment with ketamine is debated.

15. Su CJ, Liu K and Wang YM (2009). Midazolam as an effective drug for severe phantom limb pain in a patient after undergoing spinal anesthesia for two consecutive surgeries in the contralateral lower limb. Acta Anaesthesiol Taiwan 47: 32-5. Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung, and School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. Recurrence or exacerbation of phantom limb pain induced by regional anesthesia including spinal anesthesia, epidural anesthesia, and peripheral nerve block has been described in a few reports. This is a rare phenomenon, but it can occur in any amputee with or without a history of previous phantom limb pain. We describe a case whose phantom pain of the amputated limb stump was twice induced by spinal anesthesia during two consecutive surgeries in the contralateral lower limb. It was revealed that midazolam was successful in treating this rare phantom limb pain after spinal anesthesia. Here, we discuss the management of phantom limb pain during spinal anesthesia and the anesthetic management for subsequent surgery in patients with previous spinal anesthesia-induced phantom limb pain.

16. Hawamdeh ZM, Othman YS and Ibrahim AI (2008). Assessment of anxiety and depression after lower limb amputation in Jordanian patients. Neuropsychiatr Dis Treat 4: 627-33. Department of Physical Therapy, Faculty of Rehabilitation Sciences, University of Jordan Amman, Jordan. OBJECTIVE: This study aimed to assess the prevalence of anxiety and depression among Jordanian lower limb amputees with different clinical characteristics and sociodemographic data (gender, marital status, social support, income, type and level of amputation, and occupation). METHODS: Participants were 56 patients with unilateral lower limb amputation with mean duration (8.4 +/- 5.75 years). They were recruited from inpatient and outpatient clinics of Jordan University hospital, Royal Farah Rehabilitation Center, and Al-basheer hospital in Amman, Jordan. Participants responded to a questionnaire that included a battery of questions requesting brief information about sociodemographic variables and characteristics of amputation. The level of depression and anxiety in each participating patient was assessed by the Hospital Anxiety and Depression Scale (HADS). RESULTS: The prevalence of anxiety and depressive symptoms were 37% and 20%, respectively. Factors associated with high prevalence of psychological symptoms included female gender, lack of social support, unemployment, traumatic amputation, shorter time since amputation, and amputation below the knee. These findings were confirmed by a significant reduction of anxiety and depression scores in patients who received social support, patients with amputation due to disease, and patients with amputation above the knee. Presence of pain and use of prosthesis had no effect on the prevalence. CONCLUSIONS: The findings of the present study highlight the high incidence of psychiatric disability and depression in amputees; it also showed the importance of sociodemographic factors in psychological adjustment to amputation. It is suggested that psychiatric evaluation and adequate rehabilitation should form a part of their overall management.

17. Chazan S, Ekstein MP, Marouani N and Weinbroum AA (2008). Ketamine for acute and subacute pain in opioid-tolerant patients. J Opioid Manag 4: 173-80. Acute Pain Service, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Prolonged acute pain, especially that of oncologic neurological origin, is at times difficult to control; it is seldom entirely alleviated by opioids. We report eight patients with severe pain, three of whom suffered from new onset oncologic metastatic bone pain, others had previous pain syndromes and presented with exacerbation of pain. Pain was associated with hyperalgesia and allodynia phenomena in two patients and with phantom pain in a third one. Tolerance to opioids had developed, and high IV doses of morphine, meperidine or fentanyl, and patient-controlled intravenous and epidural analgesia were insufficient. Several patients became dependent on opioids and could not be weaned from assisted ventilation. Pain was controlled with decreasing adjunct doses of ketamine. Within 5-10 days of ketamine and opioid protocols, pain was controlled and after an additional 5-7 days, ketamine could be stopped and pain controlled on oral regimens compatible with outpatient care. Ketamine is an efficient adjuvant analgesic for intractable severe pain, caused by metastasis, trauma, chronic ischemia, or central neuropathic pain. It is effective even when mega doses of IV, epidural, or oral opioids prove ineffective and when signs of tolerance have developed.