Phantom pain: epidemiology and etiopathogenesis
https://doi.org/10.17749/2077-8333/epi.par.con.2025.222
Abstract
Phantom pain (PP) represents a pathological pain sensation that emerges in a person regarding a body part lost due to amputation or even naturally absent. PP occurs after amputation of both upper and lower limbs and can significantly impair patient's quality of life. Although PP descriptions have been reported since the 16th century, the precise underlying causes and pathogenesis remain obscure. Several factors, such as the site of amputation and the presence of pre-surgery pain, are associated with PP development. There are continued discussions regarding a role played by the central and peripheral nervous systems in arising PP, so that a relation between the former and neural network rewiring remain debated. The current review assesses PP epidemiology, as well as various theories behind its pathogenesis. In this context, publications included in the scientometric databases PubMed/MEDLINE, Scopus, Web of Science, Embase, and eLibrary were analyzed.
About the Authors
D. I. Korabelnikov
Moscow Haass Medical Social Institute; 1586 Military Clinical Hospital
Russian Federation
Russian Federation
Daniil I. Korabelnikov, PhD, Assoc. Prof., Prof.
Scopus Author ID: 7801382184.
5 2nd Brestskaya Str., Moscow 123056;
4 Mashtakov Str., Podolsk 142110.
Е. V. Tkachenko
Moscow Haass Medical Social Institute; Burdenko Main Military Clinical Hospital
Russian Federation
Russian Federation
Evgeny V. Tkachenko
5 2nd Brestskaya Str., Moscow 123056;
3 Gospitalnaya Sq., Moscow 105094.
M. O. Magomedaliev
Moscow Haass Medical Social Institute; 1586 Military Clinical Hospital
Russian Federation
Russian Federation
Magomedali O. Magomedaliev
Scopus Author ID: 58284748000.
5 2nd Brestskaya Str., Moscow 123056;
4 Mashtakov Str., Podolsk 142110.
References
1. Hanyu-Deutmeyer A.A., Cascella M., Varacallo M. Phantom limb pain. Treasure Island (FL): StatPearls Publishing; 2025 Jan.
2. Ramachandran V., Hirstein W. The perception of phantom limbs. The D.O. Hebb lecture. Brain. 1998; 121 (9): 1603–30. https://doi.org/10.1093/brain/121.9.1603.
3. Schone H.R., Baker C.I., Katz J., et al. Making sense of phantom limb pain. J Neurol Neurosurg Psychiatry. 2022; 93 (8): 833–43. https://doi.org/10.1136/jnnp-2021-328428.
4. Arizona P., Yulianti E., Fithriyah I. Psychiatric approach in phantom erection postpenectomy patient. Case Rep Psychiatry. 2023; 2023: 4113455. https://doi.org/10.1155/2023/4113455.
5. Limakatso K., Bedwell G.J., Madden V.J., Parker R. The prevalence and risk factors for phantom limb pain in people with amputations: a systematic review and meta-analysis. PLoS One. 2020; 15 (10): e0240431. https://doi.org/10.1371/journal.pone.0240431.
6. Federal clinical guidelines for the prevention of phantom pain syndrome in limb amputation. 2014. Available at: https://goo.su/Bmz0A (in Russ.) (accessed 26.11.2024).
7. Raimkulov B.N., Raimkulova K.B., Raimkulova H.B., et al. General characteristics of pain. Mechanism of pain development (literature review). Bulletin of the Kazakh National Medical University. 2016; 2: 324–7 (in Russ.).
8. Kaur A., Guan Y. Phantom limb pain: a literature review. Chin J Traumatol. 2018; 21 (6): 366–8. https://doi.org/10.1016/j.cjtee.2018.04.006.
9. Korabelnikov D.I., Tkachenko E.V., Magomedaliev M.O. Phantoms and phantom limbs: history of describing the phenomenon. Epilepsia i paroksizmal'nye sostoania / Epilepsy and Paroxysmal Conditions. 2024; 16 (4): 409–16 (in Russ.). https://doi.org/10.17749/2077-8333/epi.par.con.2024.219.
10. Limakatso K., Ndhlovu F., Usenbo A., et al. The prevalence and risk factors for phantom limb pain: a cross-sectional survey. BMC Neurol. 2024; 24 (1): 57. https://doi.org/10.1186/s12883-024-03547-w.
11. Priyadharshan K.P., Kumar N., Shanmugam D., et al. Quality of life in lower limb amputees: a cross-sectional study from a tertiary care center of South India. Prosthet Orthot Int. 2022; 46 (3): 246–51. https://doi.org/10.1097/PXR.0000000000000108.
12. Schley M.T., Wilms P., Toepfner S., et al. Painful and nonpainful phantom and stump sensations in acute traumatic amputees. J Trauma. 2008; 65 (4): 858–64. https://doi.org/10.1097/TA.0b013e31812eed9e.
13. Curelli A., Brouard M., Antoine P. Role of psychological factors in post-amputation phantom pain and phantom sensations. Douleurs: Evaluation – Diagnostic – Traitement. 2007; 8 (2): 65–72 (in French). https://doi.org/10.1016/S1624-5687(07)88795-6.
14. Ahmed A., Bhatnagar S., Mishra S., et al. Prevalence of phantom limb pain, stump pain, and phantom limb sensation among the amputated cancer patients in India: a prospective, observational study. Indian J Palliat Care. 2017; 23 (1): 24–35. https://doi.org/10.4103/0973-1075.197944.
15. Rahimi A., Mousavi B., Soroush M., et al. Pain and health-related quality of life in war veterans with bilateral lower limb amputations. Trauma Mon. 2012; 17 (2): 282–6. https://doi.org/10.5812/traumamon.5135.
16. Bekrater-Bodmann R., Schredl M., Diers M., et al. Post-amputation pain is associated with the recall of an impaired body representation in dreams – results from a nation-wide survey on limb amputees. PLoS One. 2015; 10 (3): e0119552. https://doi.org/10.1371/journal.pone.0119552.
17. Ayaz S.B., Ikram M., Matee S., et al. Frequency and the related sociodemographic and clinical factors of phantom limb pain in traumatic amputees presenting at a tertiary care rehabilitation setup: phantom limb pain in traumatic amputees. Pakistan Armed Forces Med J. 2015; 65 (6): 782–8.
18. Byrne K.P.A. Survey of phantom limb pain, phantom sensation and stump pain in Cambodian and New Zealand amputees. Pain Med. 2011; 12 (5): 794–8. https://doi.org/10.1111/j.1526-4637.2011.01105.x.
19. Clark R.L., Bowling F.L., Jepson F., Rajbhandari S. Phantom limb pain after amputation in diabetic patients does not differ from that after amputation in nondiabetic patients. Pain. 2013; 154 (5): 729–32. https://doi.org/10.1016/j.pain.2013.01.009.
20. Datta D., Selvarajah K., Davey N. Functional outcome of patients with proximal upper limb deficiency – acquired and congenital. Clin Rehabil. 2004; 18 (2): 172–7. https://doi.org/10.1191/0269215504cr716oa.
21. Desmond D.M., MacLachlan M. Prevalence and characteristics of phantom limb pain and residual limb pain in the long term after upper limb amputation. Int J Rehabil Res. 2010; 33 (3): 279–82. https://doi.org/10.1097/MRR.0b013e328336388d.
22. Dijkstra P.U., Geertzen J.H.B., Stewart R., van der Schans C.P. Phantom pain and risk factors: a multivariate analysis. J Pain Symptom Manage. 2002; 24 (6): 578–85. https://doi.org/10.1016/S0885-3924(02)00538-9.
23. Ehde D.M., Czerniecki J.M., Smith D.G., et al. Chronic phantom sensations, phantom pain, residual limb pain, and other regional pain after lower limb amputation. Arch Phys Med Rehabil. 2000; 81 (8): 1039–44. https://doi.org/10.1053/apmr.2000.7583.
24. Ephraim P.L., Wegener S.T., MacKenzie E.J., et al. Phantom pain, residual limb pain, and back pain in amputees: results of a national survey. Arch Phys Med Rehabil. 2005; 86 (10): 1910–9. https://doi.org/10.1016/j.apmr.2005.03.031.
25. Gallagher P., Allen D., Maclachlan M. Phantom limb pain and residual limb pain following lower limb amputation: a descriptive analysis. Disabil Rehabil. 2001; 23 (12): 522–30. https://doi.org/10.1080/09638280010029859.
26. Hanley M.A., Ehde D.M., Campbell K.M., et al. Self-reported treatments used for lower-limb phantom pain: descriptive findings. Arch Phys Med Rehabil. 2006; 87 (2): 270–7. https://doi.org/10.1016/j.apmr.2005.04.025.
27. Hanley M.A., Ehde D.M., Jensen M., et al. Chronic pain associated with upper-limb loss. Am J Phys Med Rehabil. 2009; 88 (9): 742–51. https://doi.org/10.1097/PHM.0b013e3181b306ec.
28. Hnoosh A.H. Phantom limb and pain after traumatic lower extremity amputation. J Fac Med Bagdad. 2014; 56 (1): 57–61. https://doi.org/10.32007/jfacmedbagdad.561427.
29. Houghton A.D., Nicholls G., Houghton A.L., et al. Phantom pain: natural history and association with rehabilitation. Ann R Coll Surg Engl. 1994; 76 (1): 22–5.
30. Kern U., Busch V., Müller R., et al. Phantom limb pain in daily practice – still a lot of work to do! Pain Med. 2012; 13 (12): 1611–26. https://doi.org/10.1111/j.1526-4637.2012.01494.x.
31. Ketz A.K. The experience of phantom limb pain in patients with combat-related traumatic amputations. Arch Phys Med Rehabil. 2008; 89 (6): 1127–32. https://doi.org/10.1016/j.apmr.2007.11.037.
32. Kooijman C.M., Dijkstra P.U., Geertzen J.H.B., et al. Phantom pain and phantom sensations in upper limb amputees: an epidemiological study. Pain. 2000; 87 (1): 33–41. https://doi.org/10.1016/S0304-3959(00)00264-5.
33. Larbig W., Andoh J., Huse E., et al. Pre- and postoperative predictors of phantom limb pain. Neurosci Lett. 2019; 702: 44–50. https://doi.org/10.1016/j.neulet.2018.11.044.
34. Morgan S.J., Friedly J.L., Amtmann D., et al. Cross-sectional assessment of factors related to pain intensity and pain interference in lower limb prosthesis users. Arch Phys Med Rehabil. 2017; 98 (1): 105–13. https://doi.org/10.1016/j.apmr.2016.09.118.
35. Noguchi S., Saito J., Nakai K., et al. Factors affecting phantom limb pain in patients undergoing amputation: retrospective study. J Anesth. 2019; 33 (2): 216–20. https://doi.org/10.1007/s00540-018-2599-0.
36. Probstner D., Thuler L.C., Ishikawa N.M., Alvarenga R.M. Phantom limb phenomena in cancer amputees: phantom limb phenomena in cancer amputees. Pain Pract. 2010; 10 (3): 249–56. https://doi.org/10.1111/j.1533-2500.2009.00340.x.
37. Rafferty M., Bennett Britton T.M., Drew B.T., Phillip R.D. Crosssectional study of alteration of phantom limb pain with visceral stimulation in military personnel with amputation. J Rehabil Res Dev. 2015; 52 (4): 441–8. https://doi.org/10.1682/JRRD.2014.04.0114.
38. Razmus M., Daniluk B., Markiewicz P. Phantom limb phenomenon as an example of body image distortion. Curr Probl Psychiatry. 2017; 18 (2): 153–9. https://doi.org/10.1515/cpp-2017-0013.
39. Reiber G.E., McFarland L.V., Hubbard S., et al. Servicemembers and veterans with major traumatic limb loss from Vietnam war and OIF/ OEF conflicts: survey methods, participants, and summary findings. J Rehabil Res Dev. 2010; 47 (4): 275–97. https://doi.org/10.1682/jrrd.2010.01.0009.
40. Balk E.M., Gazula A., Markozannes G., et al. Psychometric properties of functional, ambulatory, and quality of life instruments in lower limb amputees: a systematic review. Arch Phys Med Rehabil. 2019; 100 (12): 2354–70. https://doi.org/10.1016/j.apmr.2019.02.015.
41. Richardson C., Glenn S., Horgan M., Nurmikko T. 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. J Pain. 2007; 8 (10): 793–801. https://doi.org/10.1016/j.jpain.2007.05.007.
42. Richardson C., Crawford K., Milnes K., et al. A clinical evaluation of postamputation phenomena including phantom limb pain after lower limb amputation in dysvascular patients. Pain Manag Nurs. 2015; 16 (4): 561–9. https://doi.org/10.1016/j.pmn.2014.10.006.
43. Wartan S.W., Hamann W., Wedley J.R., McColl I. Phantom pain and sensation among British veteran amputees. Br J Anaesth. 1997; 78 (6): 652–9. https://doi.org/10.1093/bja/78.6.652.
44. Yin Y., Zhang L., Xiao H., et al. The pre-amputation pain and the postoperative deafferentation are the risk factors of phantom limb pain: a clinical survey in a sample of Chinese population. BMC Anesthesiol. 2017; 17 (1): 69. https://doi.org/10.1186/s12871-017-0359-6.
45. Eidmann A., Kamawal Y., Luedemann M., et al. Demographics and etiology for lower extremity amputations – experiences of an university orthopaedic center in Germany. Medicina. 2023; 59 (2): 200. https://doi.org/10.3390/medicina59020200.
46. Rivera J.A., Churovich K., Anderson A.B., Potter B.K. Estimating recent US limb loss prevalence and updating future projections. Arch Rehabil Res Clin Transl. 2024: 6 (4): 100376. https://doi.org/10.1016/j.arrct.2024.100376.
47. Ziegler-Graham K., MacKenzie E.J., Ephraim P.L., et al. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008; 89 (3): 422–9. https://doi.org/10.1016/j.apmr.2007.11.005.
48. Bernatchez J., Mayo A., Kayssi A. The epidemiology of lower extremity amputations, strategies for amputation prevention, and the importance of patient-centered care. Semin Vasc Surg. 2021; 34 (1): 54–8. https://doi.org/10.1053/j.semvascsurg.2021.02.011.
49. Yuan B., Hu D., Gu S., et al. The global burden of traumatic amputation in 204 countries and territories. Front Public Health. 2023; 11: 1258853. https://doi.org/10.3389/fpubh.2023.1258853.
50. 50 Kumar A., Soliman N., Gan Z., et al. A systematic review of the prevalence of postamputation and chronic neuropathic pain associated with combat injury in military personnel. Pain. 2024; 165 (4): 727–40. https://doi.org/10.1097/j.pain.0000000000003094.
51. Tsema Ie.V., Bespalenko A.A., Dinets A.V., et al. Study of damaging factors of contemporary war, leading to the limb loss. Novosti khirurgii. 2018; 26 (3): 321–31 (in Russ.).
52. Griffin S.C., Alphonso A.L., Tung M., et al. Characteristics of phantom limb pain in U.S. civilians and service members. Scand J Pain. 2022; 22 (1): 125–32. https://doi.org/10.1515/sjpain-2021-0139.
53. Perry B.N., Moran C.W., Armiger R.S., et al. Initial clinical evaluation of the modular prosthetic limb. Front Neurol. 2018; 9: 153. https://doi.org/10.3389/fneur.2018.00153.
54. Hirsh A.T., Dillworth T.M., Ehde D.M., Jensen M.P. Sex differences in pain and psychological functioning in persons with limb loss. J Pain. 2010; 11 (1): 79–86. https://doi.org/10.1016/j.jpain.2009.06.004.
55. Ishigami S., Boctor C. Epidemiology and risk factors for phantom limb pain. Front Pain Res. 2024; 5: 1425544. https://doi.org/10.3389/fpain.2024.1425544.
56. Eckhoff M.D., Craft M.R., Nicholson T.C., et al. Lower extremity combat sustained peripheral nerve injury in US military personnel. Plast Reconstr Surg Glob Open. 2021; 9 (3): e3447. https://doi.org/10.1097/GOX.0000000000003447.
57. Mercer S., Chavan S., Tong J.L., et al. The early detection and management of neuropathic pain following combat injury. J R Army Med Corps. 2009; 155 (2): 94–8. https://doi.org/10.1136/jramc-155-02-03.
58. Livingston K.E. The phantom limb syndrome. A discussion of the role of major peripheral nerve neuromas. J Neurosurg. 1945; 2 (3): 251–5. https://doi.org/10.3171/jns.1945.2.3.0251.
59. Issa C.J., Svientek S.R., Dehdashtian A., et al. Pathophysiological and neuroplastic changes in postamputation and neuropathic pain: review of the literature. Plast Reconstr Surg Glob Open. 2022; 10 (9): e4549. https://doi.org/10.1097/GOX.0000000000004549.
60. De Lange J.W.D., Hundepool C.A., Power D.M., et al. Prevention is better than cure: surgical methods for neuropathic pain prevention following amputation – a systematic review. J Plast Reconstr Aesthet Surg. 2022; 75 (3): 948–59. https://doi.org/10.1016/j.bjps.2021.11.076.
61. Baron R. Mechanisms of disease: neuropathic pain – a clinical perspective. Nat Rev Neurol. 2006; 2 (2): 95–106. https://doi.org/10.1038/ncpneuro0113.
62. Subedi B., Grossberg G.T. Phantom limb pain: mechanisms and treatment approaches. Pain Res Treat. 2011; 2011: 864605. https://doi.org/10.1155/2011/864605.
63. Flor H., Nikolajsen L., Staehelin Jensen T. Phantom limb pain: a case of maladaptive CNS plasticity? Nat Rev Neurosci. 2006; 7 (11): 873–81. https://doi.org/10.1038/nrn1991.
64. Yanagisawa T., Fukuma R., Seymour B., et al. Induced sensorimotor brain plasticity controls pain in phantom limb patients. Nat Commun. 2016; 7 (1): 13209. https://doi.org/10.1038/ncomms13209.
65. Reshetnyak V.K., Kukushkin M.L., Gurko N.C. Pathogenetic mechanisms of phantom-pain syndrome. Patologicheskaya fiziologiya i eksperimental’naya terapiya / Pathological physiology and experimental therapy. 2015; 59 (4): 101–7 (in Russ.).
66. Makin T.R. Phantom limb pain: thinking outside the (mirror) box. Brain. 2021; 144 (7): 1929–32. https://doi.org/10.1093/brain/awab139.
67. Katz J., Melzack R. Pain ‘memories’ in phantom limbs: review and clinical observations. Pain. 1990; 43 (3): 319–36. https://doi.org/10.1016/0304-3959(90)90029-d.
68. Ramachandran V.S., Rogers-Ramachandran D. Synaesthesia in phantom limbs induced with mirrors. Proc Biol Sci. 1996; 263 (1369): 377–86. https://doi.org/10.1098/rspb.1996.0058.
69. Makin T.R., Flor H. Brain (re)organisation following amputation: implications for phantom limb pain. Neuroimage. 2020; 218: 116943. https://doi.org/10.1016/j.neuroimage.2020.116943.
70. Andoh J., Milde C., Diers M., et al. Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective. Sci Rep. 2020; 10 (1): 11504. https://doi.org/10.1038/s41598-020-68206-9.
71. Melzack R. Phantom limbs and the concept of a neuromatrix. Trends Neurosci. 1990; 13 (3): 88–92. https://doi.org/10.1016/0166-2236(90)90179-e.
72. Melzack R. Pain and the neuromatrix in the brain. J Dent Educ. 2001; 65 (12): 1378–82.
73. Collins K.L., Russell H.G., Schumacher P.J., et al. A review of current theories and treatments for phantom limb pain. J Clin Invest. 2018; 128 (6): 2168–76. https://doi.org/10.1172/JCI94003.
74. Anderson-Barnes V.C., McAuliffe C., Swanberg K.M., Tsao J.W. Phantom limb pain – a phenomenon of proprioceptive memory? Med Hypotheses. 2009; 73 (4): 555–8. https://doi.org/10.1016/j.mehy.2009.05.038.
75. Ergenzinger E.R., Glasier M.M., Hahm J.O., Pons T.P. Cortically induced thalamic plasticity in the primate somatosensory system. Nat Neurosci. 1998; 1 (3): 226–9. https://doi.org/10.1038/673.
76. Davis K.D., Kiss Z.H., Luo L., et al. Phantom sensations generated by thalamic microstimulation. Nature. 1998; 391 (6665): 385–7. https://doi.org/10.1038/34905.
77. Waxman S.G., Hains B.C. Fire and phantoms after spinal cord injury: Na+ channels and central pain. Trends Neurosci. 2006; 29 (4): 207–15. https://doi.org/10.1016/j.tins.2006.02.003.
78. Li C.X., Chappell T.D., Ramshur J.T., Waters R.S. Forelimb amputation-induced reorganization in the ventral posterior lateral nucleus (VPL) provides a substrate for large-scale cortical reorganization in rat forepaw barrel subfield (FBS). Brain Res. 2014; 1583: 89–108. https://doi.org/10.1016/j.brainres.2014.07.022.
79. Davidson J.H., Khor K.E., Jones L.E. A cross-sectional study of post-amputation pain in upper and lower limb amputees, experience of a tertiary referral amputee clinic. Disabil Rehabil. 2010; 32 (22): 1855–62. https://doi.org/10.3109/09638281003734441.
80. Tkachenko G.A., Stepanova A.M., Merzlyakova A.M. Psychological correction of phantom pain in cancer patients. Bone and Soft Tissue Sarcomas, Tumors of the Skin. 2017; 3: 38–42 (in Russ.).
81. Bates T.J., Fergason J.R., Pierrie S.N. Technological advances in prosthesis design and rehabilitation following upper extremity limb loss. Curr Rev Musculoskelet Med. 2020; 13 (4): 485–93. https://doi.org/10.1007/s12178-020-09656-6.
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Korabelnikov D.I., Tkachenko Е.V., Magomedaliev M.O. Phantom pain: epidemiology and etiopathogenesis. Epilepsy and paroxysmal conditions. 2025;17(1):82-93. (In Russ.) https://doi.org/10.17749/2077-8333/epi.par.con.2025.222
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