Pathophysiology and treatment of phantom limb pain
Keywords:
Phantom Limb, Pain, Analgesics, Opioid, Electric stimulation, Autonomic nervous system
Abstract
Introduction:Phantom limb pain may be present in up to 80% of patients subjected to amputation because of trauma or peripheral vascular disease. Several factors have been associated with its occurrence, including pre-amputation pain, the etiology, and the amputation level.
Objective: To review the current status of the pathophysiological mechanisms, treatment options and their efficacy for the management of phantom limb pain.
Method:Non-systematic review of the literature in PubMed and Cochrane, of articles describing the pathophysiology and treatment of phantom limb pain.
Results and conclusions: The proposed pathophysiological mechanisms are still in research and include peripheral, central and psychological factors. Treatment options are still limited, and less than 10% of patients report long-term improvement.
References
1. Weeks SR, Anderson-Barnes VC, Tsao JW. Phantom limb pain: Theories and therapies. Neurologist. 2010;16:277-86.
2. Flor H, Nikolajsen L, Staehelin Jensen T. Phantom limb pain:A case of maladaptive CNS plasticity? Nat Rev Neurosci. 2006;7:873-81.
3. Nikolajsen L, Jensen TS. Phantom limb pain. Br J Anaesth. 2001;87:107-16.
4. Flor H. Phantom-limb pain: Characteristics, causes, and treatment. Lancet Neurol. 2002;1:182-9.
5. Chahine L, Kanazi G. Phantom limb syndrome: A review. Middle East J Anesthesiol. 2007;19:345-55.
6. Nathanson M. Phantom limbs as reported by S. Weir Mitchell. Neurology. 1988;38:504-5.
7. Halbert J, Crotty M, Cameron ID. Evidence for the optimal management of acute and chronic phantom pain: A systematic review. Clin J Pain. 2002;18:84-92. [ Links ]
8. Nikolajsen L, Staehelin Jensen T. Phantom limb pain. Curr Rev Pain. 2000;4:166-70.
9. Nikolajsen L. Postamputation pain: Studies on mechanisms. Dan Med J. 2012;59:B4527.
10. Bosmans JC, Geertzen JH, Post WJ, van der Schans CP, Dijkstra PU. Factors associated with phantom limb pain: A 31/2-year prospective study. Clin Rehabil. 2010;24:444-53.
11. Muller A, Sherman R, Weiss J, Addison R, Carr D, Harden RN. Neurophysiology of pain from landmine injury. Pain Med. 2006;7 Suppl 2:S204-8.
12. Wolff A, Vanduynhoven E, van Kleef M, Huygen F, Pope JE, Mekhail N. 21. Phantom pain. Pain Pract. 2011;11:403-13.
13. Gorodetskaya N, Constantin C, Janig W. Ectopic activity in cutaneous regenerating afferent nerve fibers following nerve lesion in the rat. Eur J Neurosci. 2003;18:2487-97.
14. Lasch K, Lynch NT, Rutherford K, Sherman C, Webster D. Psychological and cultural influences on pain and recovery from landmine injury. Pain Med. 2006;7 Suppl 2:S213-7.
15. Ueda H. Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms. Pharmacol Ther. 2006;109:57-77.
16. Sandkühler J. Learning and memory in pain pathways. Pain. 2000;88:113-8.
17. Huse E, Larbig W, Flor H, Birbaumer N. The effect of opioids on phantom limb pain and cortical reorganization. Pain. 2001;90:47-55.
18. Wiesenfeld-Hallin Z, Xu XJ, Hokfelt T. The role of spinal cholecystokinin in chronic pain states. Pharmacol Toxicol. 2002;91:398-403.
19. Subedi B, Grossberg GT. Phantom limb pain: Mechanisms and treatment approaches. Pain Res Treat. 2011;2011:864605.
20. Shanthanna H, Huilgol M, Manivackam VK. Early and effective use of ketamine for treatment of phantom limb pain. Indian J Anaesth. 2010;54:157-9.
21. Flórez S, León M, Torres M, Reyes F, Serpa JC, Ríos AM. Pharmacological management of neuropathic pain. Rev Colomb Anestesiol. 2009;37:356-72.
22. Wu CL, Tella P, Staats PS, Vaslav R, Kazim DA, Wesselmann U, et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: A randomized double-blind, active placebo-controlled, crossover trial. Anesthesiology. 2002;96:841-8.
23. Wu CL, Agarwal S, Tella PK, Klick B, Clark MR, Haythornthwaite JA, et al. Morphine versus mexiletine for treatment of postamputation pain: A randomized, placebo-controlled, crossover trial. Anesthesiology. 2008;109:289-96.
24. Ben Abraham R, Marouani N, Kollender Y, Meller I, Weinbroum AA. Dextromethorphan for phantom pain attenuation in cancer amputees: A double-blind crossover trial involving three patients. Clin J Pain. 2002;18:282-5.
25. Maier C, Dertwinkel R, Mansourian N, Hosbach I,Schwenkreis P, Senne I, et al. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb painâresults of a randomized double-blinded, placebo-controlled trial. Pain. 2003;103:277-83.
26. Schwenkreis P, Maier C, Pleger B, Mansourian N, Dertwinkel R, Malin JP, et al. NMDA-mediated mechanisms in cortical excitability changes after limb amputation. Acta Neurol Scand. 2003;108:179-84.
27. Wiech K, Kiefer RT, Topfner S, Preissl H, Braun C, Unertl K, et al. A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain. Anesth Analg. 2004;98:408-13.
28. Eichenberger U, Neff F, Sveticic G, Bjorgo S, Petersen-Felix S, Arendt-Nielsen L, et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesth Analg. 2008;106:1265-73.
29. Bone M, Critchley P, Buggy DJ. Gabapentin in postamputation phantom limb pain: A randomized, double-blind, placebo-controlled, cross-over study. Reg Anesth Pain Med. 2002;27:481-6.
30. Smith DG, Ehde DM, Hanley MA, Campbell KM, Jensen MP, Hoffman AJ, et al. Efficacy of gabapentin in treating chronic phantom limb and residual limb pain. J Rehabil Res Dev. 2005;42:645-54.
31. Alviar MJ, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2011;12:CD006380.
32. Patterson JF. Carbamazepine in the treatment of phantom limb pain. South Med J. 1988;81:1100-2.
33. Fang J, Lian YH, Xie KJ, Cai SN. Pharmacological interventions for phantom limb pain. Chin Med J (Engl). 2013;126:542-9.
34. Mishra S, Bhatnagar S, Singhal AK. High-dose morphine for intractable phantom limb pain. Clin J Pain. 2007;23:99-101.
35. Robinson LR, Czerniecki JM, Ehde DM, Edwards WT, Judish DA, Goldberg ML, et al. Trial of amitriptyline for relief of pain in amputees: Results of a randomized controlled study. Arch Phys Med Rehabil. 2004;85:1-6.
36. Finnerup NB, Otto M, Jensen TS, Sindrup SH. Anevidence-based algorithm for the reatment of neuropathic pain. Med Gen Med. 2007;9:36–41.
37. Jaeger H, Maier C. Calcitonin in phantom limb pain:A double-blind study. Pain. 1992;48:21-7.
38. Casale R, Ceccherelli F, Labeeb AA, Biella GE. Phantom limb pain relief by contralateral myofascial injection with local anaesthetic in a placebo-controlled study: Preliminary results. J Rehabil Med. 2009;41:418-22.
39. Lambert AW, Dashfield AK, Cosgrove C, Wilkins DC, Walker AJ, Ashley S. Randomized prospective study comparing preoperative epidural and intraoperative perineural analgesia for the prevention of postoperative stump and phantom limb pain following major amputation. Reg Anesth Pain Med. 2001;26:316-21.
40. Borghi B, d'Addabbo M, White PF, Gallerani P, Toccaceli L, Raffaeli W, et al. The use of prolonged peripheral neural blockade after lower extremity amputation: The effect on symptoms associated with phantom limb syndrome. Anesth Analg. 2010;111:1308-15.
41. Johnson M. Transcutaneous electrical nerve stimulation: Mechanisms, clinical applications and evidence. Reviews in PainâA British Pain Society Publication. 2007;1:5.
42. Mulvey MR, Bagnall AM, Johnson MI, Marchant PR. Transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults. Cochrane Database Syst Rev. 2010:CD007264.
43. Mulvey MR, Radford HE, Fawkner HJ, Hirst L, Neumann V, Johnson MI. Transcutaneous electrical nerve stimulation for phantom pain and stump pain in adult amputees. Pain Pract. 2013;13:289-96.
44. Canavero S, Bonicalzi V. Electroconvulsive therapy and pain. Pain. 2001;89:301-2.
45. Kim SY, Kim YY. Mirror therapy for phantom limb pain. Korean J Pain. 2012;25:272-4.
46. Rossi S, Tecchio F, Pasqualetti P, Ulivelli M, Pizzella V,Romani GL, et al. Somatosensory processing during movement observation in humans. Clin Neurophysiol. 2002;113:16-24.
47. Chan BL, Witt R, Charrow AP, Magee A, Howard R, Pasquina PF, et al. Mirror therapy for phantom limb pain. N Engl J Med. 2007;357:2206-7.
48. Di Rollo A, Pallanti S. Phantom limb pain: Low frequency repetitive transcranial magnetic stimulation in unaffected hemisphere. Case Report Med. 2011;2011:130751.
49. Topper R, Foltys H, Meister IG, Sparing R, Boroojerdi B. Repetitive transcranial magnetic stimulation of the parietal cortex transiently ameliorates phantom limb pain-like syndrome. Clin Neurophysiol. 2003;114:1521-30.
50. Bradbrook D. Acupuncture treatment of phantom limb pain and phantom limb sensation in amputees. Acupunct Med. 2004;22:93-7.
2. Flor H, Nikolajsen L, Staehelin Jensen T. Phantom limb pain:A case of maladaptive CNS plasticity? Nat Rev Neurosci. 2006;7:873-81.
3. Nikolajsen L, Jensen TS. Phantom limb pain. Br J Anaesth. 2001;87:107-16.
4. Flor H. Phantom-limb pain: Characteristics, causes, and treatment. Lancet Neurol. 2002;1:182-9.
5. Chahine L, Kanazi G. Phantom limb syndrome: A review. Middle East J Anesthesiol. 2007;19:345-55.
6. Nathanson M. Phantom limbs as reported by S. Weir Mitchell. Neurology. 1988;38:504-5.
7. Halbert J, Crotty M, Cameron ID. Evidence for the optimal management of acute and chronic phantom pain: A systematic review. Clin J Pain. 2002;18:84-92. [ Links ]
8. Nikolajsen L, Staehelin Jensen T. Phantom limb pain. Curr Rev Pain. 2000;4:166-70.
9. Nikolajsen L. Postamputation pain: Studies on mechanisms. Dan Med J. 2012;59:B4527.
10. Bosmans JC, Geertzen JH, Post WJ, van der Schans CP, Dijkstra PU. Factors associated with phantom limb pain: A 31/2-year prospective study. Clin Rehabil. 2010;24:444-53.
11. Muller A, Sherman R, Weiss J, Addison R, Carr D, Harden RN. Neurophysiology of pain from landmine injury. Pain Med. 2006;7 Suppl 2:S204-8.
12. Wolff A, Vanduynhoven E, van Kleef M, Huygen F, Pope JE, Mekhail N. 21. Phantom pain. Pain Pract. 2011;11:403-13.
13. Gorodetskaya N, Constantin C, Janig W. Ectopic activity in cutaneous regenerating afferent nerve fibers following nerve lesion in the rat. Eur J Neurosci. 2003;18:2487-97.
14. Lasch K, Lynch NT, Rutherford K, Sherman C, Webster D. Psychological and cultural influences on pain and recovery from landmine injury. Pain Med. 2006;7 Suppl 2:S213-7.
15. Ueda H. Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms. Pharmacol Ther. 2006;109:57-77.
16. Sandkühler J. Learning and memory in pain pathways. Pain. 2000;88:113-8.
17. Huse E, Larbig W, Flor H, Birbaumer N. The effect of opioids on phantom limb pain and cortical reorganization. Pain. 2001;90:47-55.
18. Wiesenfeld-Hallin Z, Xu XJ, Hokfelt T. The role of spinal cholecystokinin in chronic pain states. Pharmacol Toxicol. 2002;91:398-403.
19. Subedi B, Grossberg GT. Phantom limb pain: Mechanisms and treatment approaches. Pain Res Treat. 2011;2011:864605.
20. Shanthanna H, Huilgol M, Manivackam VK. Early and effective use of ketamine for treatment of phantom limb pain. Indian J Anaesth. 2010;54:157-9.
21. Flórez S, León M, Torres M, Reyes F, Serpa JC, Ríos AM. Pharmacological management of neuropathic pain. Rev Colomb Anestesiol. 2009;37:356-72.
22. Wu CL, Tella P, Staats PS, Vaslav R, Kazim DA, Wesselmann U, et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: A randomized double-blind, active placebo-controlled, crossover trial. Anesthesiology. 2002;96:841-8.
23. Wu CL, Agarwal S, Tella PK, Klick B, Clark MR, Haythornthwaite JA, et al. Morphine versus mexiletine for treatment of postamputation pain: A randomized, placebo-controlled, crossover trial. Anesthesiology. 2008;109:289-96.
24. Ben Abraham R, Marouani N, Kollender Y, Meller I, Weinbroum AA. Dextromethorphan for phantom pain attenuation in cancer amputees: A double-blind crossover trial involving three patients. Clin J Pain. 2002;18:282-5.
25. Maier C, Dertwinkel R, Mansourian N, Hosbach I,Schwenkreis P, Senne I, et al. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb painâresults of a randomized double-blinded, placebo-controlled trial. Pain. 2003;103:277-83.
26. Schwenkreis P, Maier C, Pleger B, Mansourian N, Dertwinkel R, Malin JP, et al. NMDA-mediated mechanisms in cortical excitability changes after limb amputation. Acta Neurol Scand. 2003;108:179-84.
27. Wiech K, Kiefer RT, Topfner S, Preissl H, Braun C, Unertl K, et al. A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain. Anesth Analg. 2004;98:408-13.
28. Eichenberger U, Neff F, Sveticic G, Bjorgo S, Petersen-Felix S, Arendt-Nielsen L, et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesth Analg. 2008;106:1265-73.
29. Bone M, Critchley P, Buggy DJ. Gabapentin in postamputation phantom limb pain: A randomized, double-blind, placebo-controlled, cross-over study. Reg Anesth Pain Med. 2002;27:481-6.
30. Smith DG, Ehde DM, Hanley MA, Campbell KM, Jensen MP, Hoffman AJ, et al. Efficacy of gabapentin in treating chronic phantom limb and residual limb pain. J Rehabil Res Dev. 2005;42:645-54.
31. Alviar MJ, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2011;12:CD006380.
32. Patterson JF. Carbamazepine in the treatment of phantom limb pain. South Med J. 1988;81:1100-2.
33. Fang J, Lian YH, Xie KJ, Cai SN. Pharmacological interventions for phantom limb pain. Chin Med J (Engl). 2013;126:542-9.
34. Mishra S, Bhatnagar S, Singhal AK. High-dose morphine for intractable phantom limb pain. Clin J Pain. 2007;23:99-101.
35. Robinson LR, Czerniecki JM, Ehde DM, Edwards WT, Judish DA, Goldberg ML, et al. Trial of amitriptyline for relief of pain in amputees: Results of a randomized controlled study. Arch Phys Med Rehabil. 2004;85:1-6.
36. Finnerup NB, Otto M, Jensen TS, Sindrup SH. Anevidence-based algorithm for the reatment of neuropathic pain. Med Gen Med. 2007;9:36–41.
37. Jaeger H, Maier C. Calcitonin in phantom limb pain:A double-blind study. Pain. 1992;48:21-7.
38. Casale R, Ceccherelli F, Labeeb AA, Biella GE. Phantom limb pain relief by contralateral myofascial injection with local anaesthetic in a placebo-controlled study: Preliminary results. J Rehabil Med. 2009;41:418-22.
39. Lambert AW, Dashfield AK, Cosgrove C, Wilkins DC, Walker AJ, Ashley S. Randomized prospective study comparing preoperative epidural and intraoperative perineural analgesia for the prevention of postoperative stump and phantom limb pain following major amputation. Reg Anesth Pain Med. 2001;26:316-21.
40. Borghi B, d'Addabbo M, White PF, Gallerani P, Toccaceli L, Raffaeli W, et al. The use of prolonged peripheral neural blockade after lower extremity amputation: The effect on symptoms associated with phantom limb syndrome. Anesth Analg. 2010;111:1308-15.
41. Johnson M. Transcutaneous electrical nerve stimulation: Mechanisms, clinical applications and evidence. Reviews in PainâA British Pain Society Publication. 2007;1:5.
42. Mulvey MR, Bagnall AM, Johnson MI, Marchant PR. Transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults. Cochrane Database Syst Rev. 2010:CD007264.
43. Mulvey MR, Radford HE, Fawkner HJ, Hirst L, Neumann V, Johnson MI. Transcutaneous electrical nerve stimulation for phantom pain and stump pain in adult amputees. Pain Pract. 2013;13:289-96.
44. Canavero S, Bonicalzi V. Electroconvulsive therapy and pain. Pain. 2001;89:301-2.
45. Kim SY, Kim YY. Mirror therapy for phantom limb pain. Korean J Pain. 2012;25:272-4.
46. Rossi S, Tecchio F, Pasqualetti P, Ulivelli M, Pizzella V,Romani GL, et al. Somatosensory processing during movement observation in humans. Clin Neurophysiol. 2002;113:16-24.
47. Chan BL, Witt R, Charrow AP, Magee A, Howard R, Pasquina PF, et al. Mirror therapy for phantom limb pain. N Engl J Med. 2007;357:2206-7.
48. Di Rollo A, Pallanti S. Phantom limb pain: Low frequency repetitive transcranial magnetic stimulation in unaffected hemisphere. Case Report Med. 2011;2011:130751.
49. Topper R, Foltys H, Meister IG, Sparing R, Boroojerdi B. Repetitive transcranial magnetic stimulation of the parietal cortex transiently ameliorates phantom limb pain-like syndrome. Clin Neurophysiol. 2003;114:1521-30.
50. Bradbrook D. Acupuncture treatment of phantom limb pain and phantom limb sensation in amputees. Acupunct Med. 2004;22:93-7.
How to Cite
1.
Malavera Angarita MA, Carrillo Villa S, Gomezese Ribero OF, García RG, Silva Sieger FA. Pathophysiology and treatment of phantom limb pain. Colomb. J. Anesthesiol. [Internet]. 2014 Jan. 1 [cited 2024 Apr. 24];42(1):40–46. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/624
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Published
2014-01-01
How to Cite
1.
Malavera Angarita MA, Carrillo Villa S, Gomezese Ribero OF, García RG, Silva Sieger FA. Pathophysiology and treatment of phantom limb pain. Colomb. J. Anesthesiol. [Internet]. 2014 Jan. 1 [cited 2024 Apr. 24];42(1):40–46. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/624
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Narrative review
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