Modern concepts of treatment of phantom limb pain

Abstract

Phantom limb pain is a specific entity of neuropathic pain that develops in 30%–85% of patients with amputated limbs and leads to considerable worsening of the quality of life. The number of such cases increases during military conflicts. It can be caused by a traumatic amputation due to mine blast injury, peculiarities of provided medical assistance, and the special psychological state of casualties being in extremely stressful situations at the moment of wounding. Phantom limb pain development is accompanied by multiple functional and structural changes at different levels of the peripheral and central nervous systems. As a result, different theories of pathogenesis are proposed. However, at present, no final opinion concerns mechanisms of phantom limb pain development. Although different versions of drug and non-drug therapy have been suggested, none of them turned out to be universal and fully effective. Many medications were found to be linked to phantom limb pain pathogenesis; however, even first-line therapy drugs (non-steroidal anti-inflammatory drugs, tricyclic antidepressants, narcotic analgesics, and anticonvulsants) often fail to provide adequate analgesia. Long-term prescription of narcotic analgesics is at risk of the development of addictive disorders. Surgical interventions have not demonstrated their effectiveness as well. Thus, their use is justified only in the case of ineffective conservative treatment. Poor efficacy of conventional concepts of phantom limb pain treatment led to the use of new means such as botulinum toxin therapy, non-drug methods (psychotherapy, mirror therapy, biological feedback, virtual reality, acupuncture, massage, hypnosis, etc.). Thus, the search for original methods based on the development and introduction of new drug therapy schemes is imperative. A possible solution to this problem is not only creating absolutely new non-opioid analgesics but also using adjuvant therapeutic means in the multimodality schemes of analgesia. The latter promotes neurotransmission in the antinociceptive system and potentiates the effect of traditional analgesics.

Keywords

phantom pain syndrome / phantom pain / amputation / neuropathic pain / antinociceptive system / neurotransmitter / botulinum therapy / addictive disorders

References

[1] Davydov AT, Tyukavin AI, Rezvantsev MV, et al. Phantom pain, role and place of different methods of treatment of the phantom pain syndrome. Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(1):35–58. (In Russ.). DOI: 10.17816/RCF12135-58

[2] Давыдов А.Т., Тюкавин А.И., Резванцев М.В., и др. Фантомная боль, роль и место различных методов лечения фантомно-болевого синдрома // Обзоры по клинической фармакологии и лекарственной терапии. 2014. Т. 12, № 1. С. 35–58. DOI: 10.17816/RCF12135-58

[3] Kuffler DP. Coping with phantom limb pain. Mol Neurobiol. 2018;55(1):70–84. DOI: 10.1007/s12035-017-0718-9

[4] Kuffler D.P. Coping with phantom limb pain // Mol Neurobiol. 2018. Vol. 55, No. 1. P. 70–84. DOI: 10.1007/s12035-017-0718-9

[5] Aternali A, Katz J. Recent advances in understanding and managing phantom limb pain. F1000Research. 2019;8:1167. DOI: 10.12688/f1000research.19355.1

[6] Aternali A., Katz J. Recent advances in understanding and managing phantom limb pain // F1000Research. 2019. Vol. 8. ID 1167. DOI: 10.12688/f1000research.19355.1

[7] Erlenwein J, Diers M, Ernst J, et al. Clinical updates on phantom limb pain. Pain Rep. 2021;6(1):e888. DOI: 10.1097/PR9.0000000000000888

[8] Erlenwein J., Diers M., Ernst J., et al. Clinical updates on phantom limb pain // Pain Rep. 2021. Vol. 6, No. 1. ID e888. DOI: 10.1097/PR9.0000000000000888

[9] Limakatso K, Bedwell GJ, Madden VJ, 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. DOI: 10.1371/journal.pone.0240431

[10] 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. Vol. 15, No. 10. ID e0240431. DOI: 10.1371/journal.pone.0240431

[11] Barnes JA, Eid MA, Creager MA, Goodney PP. Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease. Arterioscler Thromb Vasc Biol. 2020;40(8):1808–1817. DOI: 10.1161/ATVBAHA.120.314595

[12] Barnes J.A., Eid M.A., Creager M.A., Goodney P.P. Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease // Arterioscler Thromb Vasc Biol. 2020. Vol. 40, No. 8. P. 1808–1817. DOI: 10.1161/ATVBAHA.120.314595

[13] McDonald CL, Westcott-McCoy S, Weaver MR, et al. Global prevalence of traumatic non-fatal limb amputation. Prosthet Orthot Int. 2021;45(2):105–114. DOI: 10.1177/0309364620972258

[14] McDonald C.L., Westcott-McCoy S., Weaver M.R., et al. Global prevalence of traumatic non-fatal limb amputation // Prosthet Orthot Int. 2021. Vol. 45, No. 2. P. 105–114. DOI: 10.1177/0309364620972258

[15] Weeks SR, Anderson-Barnes VC, Tsao JW. Phantom limb pain: theories and therapies. The neurologist. 2010;16(5):277–286. DOI: 10.1097/NRL.0b013e3181edf128

[16] Weeks S.R., Anderson-Barnes V.C., Tsao J.W. Phantom limb pain: theories and therapies // The neurologist. 2010. Vol. 16, No. 5. P. 277–286. DOI: 10.1097/NRL.0b013e3181edf128

[17] Kaur A, Guan Y. Phantom limb pain: A literature review. Chin J Traumatol. 2018;21(6):366–368. DOI: 10.1016/j.cjtee.2018.04.006

[18] Kaur A., Guan Y. Phantom limb pain: A literature review // Chin J Traumatol. 2018. Vol. 21, No. 6. P. 366–368. DOI: 10.1016/j.cjtee.2018.04.006

[19] Danilov AB, Davydov OS. Neiropaticheskaya bol’. Moscow: Borges, 2007. 192 p. (In Russ.).

[20] Данилов А.Б., Давыдов О.С. Нейропатическая боль. Москва: Боргес, 2007. 192 с.

[21] Osipova NA, Sobchenko LA. Postamputatsionnyi fantomnyi bolevoi sindrom: meditsinskie i sotsial’nye problemy. Russian Journal of Anesthesiology and Reanimatology. 2011;(6):41–43. (In Russ.).

[22] Осипова Н.А., Собченко Л.А. Постампутационный фантомный болевой синдром: медицинские и социальные проблемы // Анестезиология и реаниматология. 2011. № 6. С. 41–43.

[23] Modest JM, Raducha JE, Testa EJ, Eberson CP. Management of post-amputation pain. Rhode Island medical journal. 2020;103(4): 19–22.

[24] Modest J.M., Raducha J.E., Testa E.J., Eberson C.P. Management of post-amputation pain // Rhode Island medical journal. 2020. Vol. 103, No. 4. P. 19–22.

[25] Rasulić L, Ivanović S, Bascarević V, Simić V. Phantom pain and posttraumatic pain conditions. Acta chirurgica Iugoslavica. 2004;51(4):71–80.

[26] Rasulić L., Ivanović S., Bascarević V., Simić V. Phantom pain and posttraumatic pain conditions // Acta chirurgica Iugoslavica. 2004. Vol. 51, No. 4. P. 71–80.

[27] Zhivolupov SA, Samartsev IN, Yakovlev EV. Osnovnye napravleniya v optimizatsii lecheniya bolevykh sindromov u nevrologicheskikh bol’nykh: neyrofiziologicheskiy analiz, topiko-nozologicheskaya interpretatsiya, algoritm formirovaniya bolezn’modifitsiruyushchey kompleksnoy terapii. Consilium Medicum. 2014;16(2):15–23. (In Russ.).

[28] Живолупов С.А., Самарцев И.Н., Яковлев Е.В. Основные направления в оптимизации лечения болевых синдромов у неврологических больных: нейрофизиологический анализ, топико-нозологическая интерпретация, алгоритм формирования болезньмодифицирующей комплексной терапии // Consilium Medicum. 2014. Т. 16, № 2. С. 15–23.

[29] Yam MF, Loh YC, Tan CS, et al. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci. 2018;19(8):2164–2187. DOI: 10.3390/ijms19082164

[30] Yam M.F., Loh Y.C., Tan C.S., et al. General pathways of pain sensation and the major neurotransmitters involved in pain regulation // Int J Mol Sci. 2018. Vol. 19, No. 8. P. 2164–2187. DOI: 10.3390/ijms19082164

[31] Collins KL, Russell HG, Schumacher PJ, et al. A review of current theories and treatments for phantom limb pain. J Clin Investig. 2018;128(6):2168–2176. DOI: 10.1172/JCI94003

[32] Collins K.L., Russell H.G., Schumacher P.J., et al. A review of current theories and treatments for phantom limb pain // J Clin Investig. 2018. Vol. 128, No. 6. P. 2168–2176. DOI: 10.1172/JCI94003

[33] Lee GI, Neumeister MW. Pain: pathways and physiology. Clin Plast Surg. 2020;47(2):173–180. DOI: 10.1016/j.cps.2019.11.001

[34] Lee G.I., Neumeister M.W. Pain: pathways and physiology // Clin Plast Surg. 2020. Vol. 47, No. 2. P. 173–180. DOI: 10.1016/j.cps.2019.11.001

[35] Millan MJ. Descending control of pain. Prog Neurobiol. 2002;66(6):355–474. DOI: 10.1016/s0301-0082(02)00009-6

[36] Millan M.J. Descending control of pain // Prog Neurobiol. 2002. Vol. 66, No. 6. P. 355–474. DOI: 10.1016/s0301-0082(02)00009-6

[37] Park J, Chung ME. Botulinum toxin for central neuropathic pain. Toxins (Basel). 2018;10(6):224. DOI: 10.3390/toxins10060224

[38] Park J., Chung M.E. Botulinum toxin for central neuropathic pain // Toxins (Basel). 2018. Vol. 10, No. 6. ID 224. DOI: 10.3390/toxins10060224

[39] Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150(3699):971–979. DOI: 10.1126/science.150.3699.971

[40] Melzack R., Wall P.D. Pain mechanisms: a new theory // Science. 1965. Vol. 150, No. 3699. P. 971–979. DOI: 10.1126/science.150.3699.971

[41] Selye H. Stress and the general adaptation syndrome. Br Med J. 1950;1(4667):1383–1392. DOI: 10.1136/bmj.1.4667.1383

[42] Selye H. Stress and the general adaptation syndrome // Br Med J. 1950. Vol. 1, No. 4667. P. 1383–1392. DOI: 10.1136/bmj.1.4667.1383

[43] Melzack R. Pain and the neuromatrix in the brain. J Dent Educ. 2001;65(12):1378–1382. DOI: 10.1002/j.0022-0337.2001.65.12.tb03497.x

[44] Melzack R. Pain and the neuromatrix in the brain // J Dent Educ. 2001. Vol. 65, No. 12. P. 1378–1382. DOI: 10.1002/j.0022-0337.2001.65.12.tb03497.x

[45] Ramachandran VS, Hirstein W. The perception of phantom limbs: the D.O. Hebb lecture. Brain. 1998;121(9):1603–1630. DOI: 10.1093/brain/121.9.1603

[46] Ramachandran V.S., Hirstein W. The perception of phantom limbs: the D.O. Hebb lecture // Brain. 1998. Vol. 121, No. 9. P. 1603–1630. DOI: 10.1093/brain/121.9.1603

[47] Anokhin PK. Ocherki po fiziologii funktsional’nykh sistem. Moscow: Meditsina, 1975. 448 p. (In Russ.).

[48] Анохин П.К. Очерки по физиологии функциональных систем. Москва: Медицина, 1975. 448 с.

[49] Orbeli LA. Izbrannye trudy. Adaptatsionno-troficheskaya funktsiya nervnoi sistemy. Moscow: Akademiya nauk SSSR, 1962. 608 p. (In Russ.).

[50] Орбели Л.А. Избранные труды. Адаптационно-трофическая функция нервной системы. Москва: Академия наук СССР, 1962. 608 с.

[51] Kryzhanovskii GN. Generatornye, determinantnye i sistemnye mekhanizmy rasstroistv tsentral’noi nervnoi sistemy. Soviet Neurology and Psychiatry. 1990;90(10):3–10. (In Russ.).

[52] Крыжановский Г.Н. Генераторные, детерминантные и системные механизмы расстройств центральной нервной системы // Журнал неврологии и психиатрии им. С.С. Корсакова. 1990. Т. 90, № 10. С. 3–10.

[53] Ukhtomskii AA. Sobranie sochinenii. T. 1. Leningrad: LGU, 1950. 329 p. (In Russ.).

[54] Ухтомский А.А. Собрание сочинений. Т. 1. Ленинград: ЛГУ, 1950. 329 с.

[55] Georgii Nikolaevich Kryzhanovskii. Annals of the Russian academy of medical sciences. 2012;(11):66–67. (In Russ.).

[56] Георгий Николаевич Крыжановский // Вестник РАМН. 2012. № 11. С. 66–67.

[57] Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care. 2014;8(2):143–151. DOI: 10.1097/SPC.0000000000000055

[58] Ossipov M.H., Morimura K., Porreca F. Descending pain modulation and chronification of pain // Curr Opin Support Palliat Care. 2014. Vol. 8, No. 2. P. 143–151. DOI: 10.1097/SPC.0000000000000055

[59] Jensen TS, Gottrup H, Sindrup SH, Bach FW. The clinical picture of neuropathic pain. Eur J Pharmacol. 2001;429(1-3):1–11. DOI: 10.1016/s0014-2999(01)01302-4

[60] Jensen T.S., Gottrup H., Sindrup S.H., Bach F.W. The clinical picture of neuropathic pain // Eur J Pharmacol. 2001. Vol. 429, No. 1-3. P. 1–11. DOI: 10.1016/s0014-2999(01)01302-4

[61] Wang XQ, Mokhtari T, Zeng YX, et al. The distinct functions of dopaminergic receptors on pain modulation: A narrative review. Neural Plast. 2021;2021:6682275. DOI: 10.1155/2021/6682275

[62] Wang X.Q., Mokhtari T., Zeng Y.X., et al. The distinct functions of dopaminergic receptors on pain modulation: A narrative review // Neural Plast. 2021. Vol. 2021. ID 6682275. DOI: 10.1155/2021/6682275

[63] Obata H. Analgesic mechanisms of antidepressants for neuropathic pain. Int J Mol Sci. 2017;18(11):2483. DOI: 10.3390/ijms18112483

[64] Obata H. Analgesic mechanisms of antidepressants for neuropathic pain // Int J Mol Sci. 2017. Vol. 18, No. 11. ID 2483. DOI: 10.3390/ijms18112483

[65] Li C, Liu S, Lu X, Tao F. Role of descending dopaminergic pathways in pain modulation. Curr Neuropharmacol. 2019;17(12):1176–1182. DOI: 10.2174/1570159X17666190430102531

[66] Li C., Liu S., Lu X., Tao F. Role of descending dopaminergic pathways in pain modulation // Curr Neuropharmacol. 2019. Vol. 17, No. 12. P. 1176–1182. DOI: 10.2174/1570159X17666190430102531

[67] Liu S, Tang Y, Shu H, et al. Dopamine receptor D2, but not D1, mediates descending dopaminergic pathway-produced analgesic effect in a trigeminal neuropathic pain mouse model. Pain. 2019;160(2):334–344. DOI: 10.1097/j.pain.0000000000001414

[68] Liu S., Tang Y., Shu H., et al. Dopamine receptor D2, but not D1, mediates descending dopaminergic pathway-produced analgesic effect in a trigeminal neuropathic pain mouse model // Pain. 2019. Vol. 160, No. 2. P. 334–344. DOI: 10.1097/j.pain.0000000000001414

[69] Lançon K, Qu C, Navratilova E, et al. Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain. Cell Rep. 2021;37(9):109933. DOI: 10.1016/j.celrep.2021.109933

[70] Lançon K., Qu C., Navratilova E., et al. Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain // Cell Rep. 2021. Vol. 37, No. 9. ID 109933. DOI: 10.1016/j.celrep.2021.109933

[71] Ertas M, Sagduyu A, Arac N, et al. Use of levodopa to relieve pain from painful symmetrical diabetic polyneuropathy. Pain. 1998;75 (2-3):257–259. DOI: 10.1016/s0304-3959(98)00003-7

[72] Ertas M., Sagduyu A., Arac N., et al. Use of levodopa to relieve pain from painful symmetrical diabetic polyneuropathy // Pain. 1998. Vol. 75, No. 2-3. P. 257–259. DOI: 10.1016/s0304-3959(98)00003-7

[73] Mercado-Reyes J, Almanza A, Segura-Chama P, et al. D2-like receptor agonist synergizes the μ-opioid agonist spinal antinociception in nociceptive, inflammatory and neuropathic models of pain in the rat. Eur J Pharmacol. 2019;853:56–64. DOI: 10.1016/j.ejphar.2019.03.020

[74] Mercado-Reyes J., Almanza A., Segura-Chama P., et al. D2-like receptor agonist synergizes the μ-opioid agonist spinal antinociception in nociceptive, inflammatory and neuropathic models of pain in the rat // Eur J Pharmacol. 2019. Vol. 853. P. 56–64. DOI: 10.1016/j.ejphar.2019.03.020

[75] Rodgers HM, Lim S-A, Yow J, et al. Dopamine D1 or D3 receptor modulators prevent morphine tolerance and reduce opioid withdrawal symptoms. Pharmacol Biochem Behav. 2020;194:172935. DOI: 10.1016/j.pbb.2020.172935

[76] Rodgers H.M., Lim S.-A., Yow J., et al. Dopamine D1 or D3 receptor modulators prevent morphine tolerance and reduce opioid withdrawal symptoms // Pharmacol Biochem Behav. 2020. Vol. 194. ID 172935. DOI: 10.1016/j.pbb.2020.172935

[77] Tobaldini G, Reis RA, Sardi NF, et al. Dopaminergic mechanisms in periaqueductal gray-mediated antinociception. Behav Pharmacol. 2018;29(2-3):225–233. DOI: 10.1097/FBP.0000000000000346

[78] Tobaldini G., Reis R.A., Sardi N.F., et al. Dopaminergic mechanisms in periaqueductal gray-mediated antinociception // Behav Pharmacol. 2018. Vol. 29, No. 2-3. P. 225–233. DOI: 10.1097/FBP.0000000000000346

[79] Kim J-Y, Tillu DV, Quinn TL, et al. Spinal dopaminergic projections control the transition to pathological pain plasticity via a D1/D5-mediated mechanism. J Neurosci. 2015;35(16):6307–6317. DOI: 10.1523/JNEUROSCI.3481-14.2015

[80] Kim J.-Y., Tillu D.V., Quinn T.L., et al. Spinal dopaminergic projections control the transition to pathological pain plasticity via a D1/D5-mediated mechanism // J Neurosci. 2015. Vol. 35, No. 16. P. 6307–6317. DOI: 10.1523/JNEUROSCI.3481-14.2015

[81] Igon’kina SI, Grafova VN, Smirnova VS, et al. Ehksperimental’noe issledovanie roli immunologicheskogo faktora v patogeneze nevropaticheskoi boli. Russian Journal of Pain. 2013;(1):10. (In Russ.).

[82] Игонькина С.И., Графова В.Н., Смирнова В.С., и др. Экспериментальное исследование роли иммунологического фактора в патогенезе невропатической боли // Российский журнал боли. 2013. № 1. С. 10.

[83] Igon’kina SI, Kukushkin ML, Vetrileh LA, et al. Antitela k neiromediatoram antinotsitseptivnoi sistemy usilivayut i prolongiruyut nevropaticheskuyu bol’. Russian Journal of Pain. 2014;(1):15–16. (In Russ.).

[84] Игонькина С.И., Кукушкин М.Л., Ветрилэ Л.А., и др. Антитела к нейромедиаторам антиноцицептивной системы усиливают и пролонгируют невропатическую боль // Российский журнал боли. 2014. № 1. С. 15–16.

[85] Alviar MJ, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2016;10(10):CD006380.pub3. DOI: 10.1002/14651858.CD006380.pub3

[86] Alviar M.J., Hale T., Dungca M. Pharmacologic interventions for treating phantom limb pain // Cochrane Database Syst Rev. 2016. Vol. 10, No. 10. ID CD006380.pub3. DOI: 10.1002/14651858.CD006380.pub3

[87] Kremer M, Salvat E, Muller A, et al. Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights. Neuroscience. 2016;338:183–206. DOI: 10.1016/j.neuroscience.2016.06.057

[88] Kremer M., Salvat E., Muller A., et al. Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights // Neuroscience. 2016. Vol. 338. P. 183–206. DOI: 10.1016/j.neuroscience.2016.06.057

[89] Subedi B, Grossberg GT. Phantom limb pain: mechanisms and treatment approaches. Pain Res Treatment. 2011;2011:864605. DOI: 10.1155/2011/864605

[90] Subedi B., Grossberg G.T. Phantom limb pain: mechanisms and treatment approaches // Pain Res Treatment. 2011. Vol. 2011. ID 864605. DOI: 10.1155/2011/864605

[91] Andreeva GO. Khronicheskii bolevoi sindrom pri zabolevaniyakh perifericheskoi nervnoi sistemy [dissertation]. Saint Petersburg; 2015. 282 p. (In Russ.).

[92] Андреева Г.О. Хронический болевой синдром при заболеваниях периферической нервной системы: дис. … д-ра мед. наук. Санкт-Петербург, 2015. 282 с.

[93] Robinson LR, Czerniecki JM, Ehde DM, et al. Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. Arch Phys Med Rehabil. 2004;85(1):1–6. DOI: 10.1016/s0003-9993(03)00476-3

[94] Robinson L.R., Czerniecki J.M., Ehde D.M., et al. Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study // Arch Phys Med Rehabil. 2004. Vol. 85, No. 1. P. 1–6. DOI: 10.1016/s0003-9993(03)00476-3

[95] Bone M, Critchley P, Buggy DJ. Gabapentin in postamputation phantom limb pain: a randomized, double-blind, placebocontrolled, cross-over study. Reg Anesth Pain Med. 2002;27(5):481–486. DOI: 10.1053/rapm.2002.35169

[96] Bone M., Critchley P., Buggy D.J. Gabapentin in postamputation phantom limb pain: a randomized, double-blind, placebocontrolled, cross-over study // Reg Anesth Pain Med. 2002. Vol. 27, No. 5. P. 481–486. DOI: 10.1053/rapm.2002.35169

[97] Smith D, Ehde D, Hanley M, et al. Efficacy of gabapentin in treating chronic phantom limb and residual limb pain. J Rehabil Res Dev. 2005;42(5):645–654. DOI: 10.1682/jrrd.2005.05.0082

[98] Smith D., Ehde D., Hanley M., et al. Efficacy of gabapentin in treating chronic phantom limb and residual limb pain // J Rehabil Res Dev. 2005. Vol. 42, No. 5. P. 645–654. DOI: 10.1682/jrrd.2005.05.0082

[99] Huse E, Larbig W, Flor H, Birbaumer N. The effect of opioids on phantom limb pain and cortical reorganization. Pain. 2001;90 (1-2):47–55. DOI: 10.1016/s0304-3959(00)00385-7

[100] Huse E., Larbig W., Flor H., Birbaumer N. The effect of opioids on phantom limb pain and cortical reorganization // Pain. 2001. Vol. 90, No. 1-2. P. 47–55. DOI: 10.1016/s0304-3959(00)00385-7

[101] Wu CL, Agarwal S, Tella PK, et al. Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebocontrolled, crossover trial. Anesthesiology. 2008;109(2):289–296. DOI: 10.1097/ALN.0b013e31817f4523

[102] Wu C.L., Agarwal S., Tella P.K., et al. Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebocontrolled, crossover trial // Anesthesiology. 2008. Vol. 109, No. 2. P. 289–296. DOI: 10.1097/ALN.0b013e31817f4523

[103] Eichenberger U, Neff F, Sveticic G, et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesthesia and Analgesia. 2008;106(4):1265–1273. DOI: 10.1213/ane.0b013e3181685014

[104] Eichenberger U., Neff F., Sveticic G., et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds // Anesthesia and Analgesia. 2008. Vol. 106, No. 4. P. 1265–1273. DOI: 10.1213/ane.0b013e3181685014

[105] Neil MJE, Dale MC, Gillespie G. Successful use of Memantine in the treatment of severe phantom limb pain: case report and literature review. Scott Med J. 2010;55(2):58. DOI: 10.1258/rsmsmj.55.2.58b

[106] Neil M.J.E., Dale M.C., Gillespie G. Successful use of Memantine in the treatment of severe phantom limb pain: case report and literature review // Scott Med J. 2010. Vol. 55, No. 2. P. 58. DOI: 10.1258/rsmsmj.55.2.58b

[107] Maier C, Dertwinkel R, Mansourian N, et al. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain – results of a randomized double-blinded, placebo-controlled trial. Pain. 2003;103(3):277–283. DOI: 10.1016/S0304-3959(02)00456-6

[108] Maier C., Dertwinkel R., Mansourian N., et al. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain – results of a randomized double-blinded, placebo-controlled trial // Pain. 2003. Vol. 103, No. 3. P. 277–283. DOI: 10.1016/S0304-3959(02)00456-6

[109] Wiech K, Kiefer R-T, Töpfner S, 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. Anesthesia and analgesia. 2004;98(2):408–413. DOI: 10.1213/01.ANE.0000096002.53818.BD

[110] Wiech K., Kiefer R.-T., Töpfner S., 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 // Anesthesia and analgesia. 2004. Vol. 98, No. 2. P. 408–413. DOI: 10.1213/01.ANE.0000096002.53818.BD

[111] Abraham RB, Marouani N, Weinbroum AA. Dextromethorphan mitigates phantom pain in cancer amputees. Ann Surg Oncol. 2003;10(3):268–274. DOI: 10.1245/aso.2003.08.007

[112] Abraham R.B., Marouani N., Weinbroum A.A. Dextromethorphan mitigates phantom pain in cancer amputees // Ann Surg Oncol. 2003. Vol. 10, No. 3. P. 268–274. DOI: 10.1245/aso.2003.08.007

[113] Nikolajsen L, Hansen C, Nielsen J, et al. The effect of ketamine on phantom pain: a central neuropathic disorder maintained by peripheral input. Pain. 1996;67(1):69–77. DOI: 10.1016/0304-3959(96)03080-1

[114] Nikolajsen L., Hansen C., Nielsen J., et al. The effect of ketamine on phantom pain: a central neuropathic disorder maintained by peripheral input // Pain. 1996. Vol. 67, No. 1. P. 69–77. DOI: 10.1016/0304-3959(96)03080-1

[115] Elavarasi A, Goyal V. Botulinum toxin to treat phantom limb pain. Toxicon. 2021;195:17–19. DOI: 10.1016/j.toxicon.2021.02.010

[116] Elavarasi A., Goyal V. Botulinum toxin to treat phantom limb pain // Toxicon. 2021. Vol. 195. P. 17–19. DOI: 10.1016/j.toxicon.2021.02.010

[117] Wu H, Sultana R, Taylor KB, Szabo A. Prospective randomized double-blinded pilot study to examine the effect of botulinum toxin type A injection versus Lidocaine/Depomedrol injection on residual and phantom limb pain: initial report. Clin J Pain. 2012;28(2):108–112. DOI: 10.1097/AJP.0b013e3182264fe9

[118] Wu H., Sultana R., Taylor K.B., Szabo A. Prospective randomized double-blinded pilot study to examine the effect of botulinum toxin type A injection versus Lidocaine/Depomedrol injection on residual and phantom limb pain: initial report // Clin J Pain. 2012. Vol. 28, No. 2. P. 108–112. DOI: 10.1097/AJP.0b013e3182264fe9

[119] Khanna A. Anatomiya spinnomozgovykh nervov i dostupy k nim. Saint Petersburg: Spetslit; 2020. 151 p. (In Russ.).

[120] Ханна А. Анатомия спинномозговых нервов и доступы к ним. Санкт-Петербург: Спецлит, 2020. 151 с.

[121] Zhurbin EA. Vozmozhnosti ul’trazvukovogo issledovaniya pri travmaticheskikh povrezhdeniyakh perifericheskikh nervov konechnostei [dissertation]. Saint Petersburg; 2018. 147 p. (In Russ.).

[122] Журбин Е.А. Возможности ультразвукового исследования при травматических повреждениях периферических нервов конечностей: дис. … канд. мед. наук. Санкт-Петербург, 2018. 147 с.

RIGHTS & PERMISSIONS

Eco-Vector