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Pharmacological and Non-pharmacological Approaches for the Management of Neuropathic Pain in Multiple Sclerosis

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Abstract

Multiple sclerosis is a chronic inflammatory disease that affects the central nervous system and can cause various types of pain including ongoing extremity pain, Lhermitte’s phenomenon, trigeminal neuralgia, and mixed pain. Neuropathic pain is a major concern for individuals with multiple sclerosis as it is directly linked to myelin damage in the central nervous system and the management of neuropathic pain in multiple sclerosis is challenging as the options available have limited efficacy and can cause unpleasant side effects. The literature search was conducted across two databases, PubMed, and Google Scholar. Eligible studies included clinical trials, observational studies, meta-analyses, systematic reviews, and narrative reviews. The objective of this article is to provide an overview of literature on pharmacological and non-pharmacological strategies employed in the management of neuropathic pain in multiple sclerosis. Pharmacological options include cannabinoids, muscle relaxants (tizanidine, baclofen, dantrolene), anticonvulsants (benzodiazepines, gabapentin, phenytoin, carbamazepine, lamotrigine), antidepressants (duloxetine, venlafaxine, tricyclic antidepressants), opioids (naltrexone), and botulinum toxin variants, which have evidence from various clinical trials. Non-pharmacological approaches for trigeminal neuralgia may include neurosurgical methods. Non-invasive methods, physical therapy, and psychotherapy (cognitive behavioral therapy, acceptance and commitment therapy and mindfulness-based stress reduction) may be recommended for patients with neuropathic pain in multiple sclerosis. The choice of treatment depends on the severity and type of pain as well as other factors, such as patient preferences and comorbidities. There is a pressing need for healthcare professionals and researchers to prioritize the development of better strategies for managing multiple sclerosis-induced neuropathic pain.

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References

  1. Leray E, Moreau T, Fromont A, Edan G. Epidemiology of multiple sclerosis. Rev Neurol (Paris). 2016;172:3–13. https://doi.org/10.1016/j.neurol.2015.10.006.

    Article  CAS  PubMed  Google Scholar 

  2. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: insights from the atlas of MS, third edition. Mult Scler J. 2020;26:1816–21. https://doi.org/10.1177/1352458520970841.

    Article  Google Scholar 

  3. Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, et al. Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity. Neurology. 2014;83:1022–4. https://doi.org/10.1212/WNL.0000000000000768.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Chisari CG, Sgarlata E, Arena S, D’Amico E, Toscano S, Patti F. An update on the pharmacological management of pain in patients with multiple sclerosis. Expert Opin Pharmacother. 2020;21:2249–63. https://doi.org/10.1080/14656566.2020.1757649.

    Article  CAS  PubMed  Google Scholar 

  5. Svendsen KB, Jensen TS, Overvad K, Hansen HJ, Koch-Henriksen N, Bach FW. Pain in patients with multiple sclerosis. Arch Neurol. 2003;60:1089. https://doi.org/10.1001/archneur.60.8.1089.

    Article  PubMed  Google Scholar 

  6. O’Connor AB, Schwid SR, Herrmann DN, Markman JD, Dworkin RH. Pain associated with multiple sclerosis: systematic review and proposed classification. Pain. 2008;137:96–111. https://doi.org/10.1016/j.pain.2007.08.024.

    Article  PubMed  Google Scholar 

  7. Truini A, Barbanti P, Pozzilli C, Cruccu G. A mechanism-based classification of pain in multiple sclerosis. J Neurol. 2013;260:351–67. https://doi.org/10.1007/s00415-012-6579-2.

    Article  CAS  PubMed  Google Scholar 

  8. Khan N, Smith MT. Multiple sclerosis-induced neuropathic pain: pharmacological management and pathophysiological insights from rodent EAE models. Inflammopharmacology. 2014;22:1–22. https://doi.org/10.1007/s10787-013-0195-3.

    Article  CAS  PubMed  Google Scholar 

  9. Foley PL, Vesterinen HM, Laird BJ, Sena ES, Colvin LA, Chandran S, et al. Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis. Pain. 2013;154:632–42. https://doi.org/10.1016/j.pain.2012.12.002.

    Article  PubMed  Google Scholar 

  10. Nurmikko TJ, Gupta S, Maclver K. Multiple sclerosis-related central pain disorders. Curr Pain Headache Rep. 2010;14:189–95. https://doi.org/10.1007/s11916-010-0108-8.

    Article  PubMed  Google Scholar 

  11. Feketová S, Waczulíková I, Valkovič P, Mareš J. Central pain in patients with multiple sclerosis. J Mult Scler. 2017. https://doi.org/10.4172/2376-0389.1000208.

    Article  Google Scholar 

  12. Solaro C, Cella M, Signori A, Martinelli V, Radaelli M, Centonze D, et al. Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria. J Neurol. 2018;265:828–35. https://doi.org/10.1007/s00415-018-8758-2.

    Article  PubMed  Google Scholar 

  13. Drulovic J, Basic-Kes V, Grgic S, Vojinovic S, Dincic E, Toncev G, et al. The prevalence of pain in adults with multiple sclerosis: a multicenter cross-sectional survey. Pain Med. 2015;16:1597–602. https://doi.org/10.1111/pme.12731.

    Article  PubMed  Google Scholar 

  14. Heitmann H, Haller B, Tiemann L, Mühlau M, Berthele A, Tölle TR, et al. Longitudinal prevalence and determinants of pain in multiple sclerosis: results from the German National Multiple Sclerosis Cohort study. Pain. 2020;161:787–96. https://doi.org/10.1097/j.pain.0000000000001767.

    Article  PubMed  Google Scholar 

  15. Kahraman T, Özdoğar AT, Ertekin Ö, Özakbaş S. Frequency, type, distribution of pain and related factors in persons with multiple sclerosis. Mult Scler Relat Disord. 2019;28:221–5. https://doi.org/10.1016/j.msard.2019.01.002.

    Article  PubMed  Google Scholar 

  16. Karakas H, Kaya E, Abasiyanik Z, Ozdogar AT. Investigation of neuropathic pain distribution and related factors in people with multiple sclerosis. J Mult Scler Res. 2022;2:46–51. https://doi.org/10.4274/jmsr.galenos.2022.2022-7-2.

    Article  Google Scholar 

  17. Kasap Z, Uğurlu H. Pain in patients with multiple sclerosis. Turk J Phys Med Rehabil. 2023;1:31–9. https://doi.org/10.5606/tftrd.2022.10524.

    Article  Google Scholar 

  18. Hadjimichael O, Kerns RD, Rizzo MA, Cutter G, Vollmer T. Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain. 2007;127:35–41. https://doi.org/10.1016/j.pain.2006.07.015.

    Article  PubMed  Google Scholar 

  19. Murphy KL, Bethea Jr, Fischer R. Neuropathic pain in multiple sclerosis: current therapeutic intervention and future treatment perspectives. In: Zagon IS, McLaughlin PJ, editors. Multiple sclerosis: perspectives in treatment and pathogenesis. Brisbane: Codon Publications; 2017, p. 53–69. https://doi.org/10.15586/codon.multiplesclerosis.2017.ch4.

  20. Aboud T, Schuster NM. Pain management in multiple sclerosis: a review of available treatment options. Curr Treat Opt Neurol. 2019;21:62. https://doi.org/10.1007/s11940-019-0601-2.

    Article  Google Scholar 

  21. Watson JC, Sandroni P. Central neuropathic pain syndromes. Mayo Clin Proc. 2016;91:372–85. https://doi.org/10.1016/j.mayocp.2016.01.017.

    Article  PubMed  Google Scholar 

  22. Solaro C, Brichetto G, Amato MP, Cocco E, Colombo B, D’Aleo G, et al. The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study. Neurology. 2004;63:919–21. https://doi.org/10.1212/01.WNL.0000137047.85868.D6.

    Article  CAS  PubMed  Google Scholar 

  23. Racke MK, Frohman EM, Frohman T. Pain in multiple sclerosis: understanding pathophysiology, diagnosis, and management through clinical vignettes. Front Neurol. 2022;12: 799698. https://doi.org/10.3389/fneur.2021.799698.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Urits I, Adamian L, Fiocchi J, Hoyt D, Ernst C, Kaye AD, et al. Advances in the understanding and management of chronic pain in multiple sclerosis: a comprehensive review. Curr Pain Headache Rep. 2019;23:59. https://doi.org/10.1007/s11916-019-0800-2.

    Article  PubMed  Google Scholar 

  25. Klit H, Finnerup NB, Andersen G, Jensen TS. Central poststroke pain: a population-based study. Pain. 2011;152:818–24. https://doi.org/10.1016/j.pain.2010.12.030.

    Article  PubMed  Google Scholar 

  26. Mirabelli E, Elkabes S. Neuropathic pain in multiple sclerosis and its animal models: focus on mechanisms, knowledge gaps and future directions. Front Neurol. 2021;12: 793745. https://doi.org/10.3389/fneur.2021.793745.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Browne TJ, Hughes DI, Dayas CV, Callister RJ, Graham BA. Projection neuron axon collaterals in the dorsal horn: placing a new player in spinal cord pain processing. Front Physiol. 2020;11: 560082. https://doi.org/10.3389/fphys.2020.560802.

    Article  Google Scholar 

  28. Dworsky-Fried Z, Faig CA, Vogel HA, Kerr BJ, Taylor AMW. Central amygdala inflammation drives pain hypersensitivity and attenuates morphine analgesia in experimental autoimmune encephalomyelitis. Pain. 2022;163:e49-61. https://doi.org/10.1097/j.pain.0000000000002307.

    Article  CAS  PubMed  Google Scholar 

  29. Svendsenl KB, Sørensenl L, Jensenl TS, Hansenl HJ, Bachl FW. MRI of the central nervous system in MS patients with and without pain. Eur J Pain. 2011;15:395–401. https://doi.org/10.1016/j.ejpain.2010.09.006.

    Article  Google Scholar 

  30. Plantone D, Vollono C, Pardini M, Primiano G, Myftari V, Vitetta F, et al. A voxel-based lesion symptom mapping analysis of chronic pain in multiple sclerosis. Neurol Sci. 2021;42:1941–7. https://doi.org/10.1007/s10072-020-04745-3.

    Article  PubMed  Google Scholar 

  31. Doolen S, Iannitti T, Donahue RR, Shaw BC, Grachen CM, Taylor BK. Fingolimod reduces neuropathic pain behaviors in a mouse model of multiple sclerosis by a sphingosine-1 phosphate receptor 1-dependent inhibition of central sensitization in the dorsal horn. Pain. 2018;159:224–38. https://doi.org/10.1097/j.pain.0000000000001106.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10:895–926. https://doi.org/10.1016/j.jpain.2009.06.012.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Baron R, Hans G, Dickenson AH. Peripheral input and its importance for central sensitization. Ann Neurol. 2013;74:630–6. https://doi.org/10.1002/ana.24017.

    Article  PubMed  Google Scholar 

  34. Tao Y-X. AMPA receptor trafficking in inflammation-induced dorsal horn central sensitization. Neurosci Bull. 2012;28:111–20. https://doi.org/10.1007/s12264-012-1204-z.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Mao L-M, Liu X-Y, Zhang G-C, Chu X-P, Fibuch EE, Wang LS, et al. Phosphorylation of group I metabotropic glutamate receptors (mGluR1/5) in vitro and in vivo. Neuropharmacology. 2008;55:403–8. https://doi.org/10.1016/j.neuropharm.2008.05.034.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Tang J, Bair M, Descalzi G. Reactive astrocytes: critical players in the development of chronic pain. Front Psychiatry. 2021;12: 682056. https://doi.org/10.3389/fpsyt.2021.682056.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Warfield AE, Prather JF, Todd WD. Systems and circuits linking chronic pain and circadian rhythms. Front Neurosci. 2021;15: 705173. https://doi.org/10.3389/fnins.2021.705173.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Aborode AT, Pustake M, Awuah WA, Alwerdani M, Shah P, Yarlagadda R, et al. Targeting oxidative stress mechanisms to treat Alzheimer’s and Parkinson’s disease: a critical review. Oxid Med Cell Longev. 2022;2022:1–9. https://doi.org/10.1155/2022/7934442.

    Article  CAS  Google Scholar 

  39. Boiko DI, Shkodina AD, Hasan MM, Bardhan M, Kazmi SK, Chopra H, et al. Melatonergic receptors (Mt1/Mt2) as a potential additional target of novel drugs for depression. Neurochem Res. 2022;47:2909–24. https://doi.org/10.1007/s11064-022-03646-5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Zhuo M. Descending facilitation. Mol Pain. 2017;13:174480691769921. https://doi.org/10.1177/1744806917699212.

    Article  Google Scholar 

  41. Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care. 2014;8:143–51. https://doi.org/10.1097/SPC.0000000000000055.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Papadopoulou A, Naegelin Y, Weier K, Amann M, Hirsch J, von Felten S, et al. MRI characteristics of periaqueductal lesions in multiple sclerosis. Mult Scler Relat Disord. 2014;3:542–51. https://doi.org/10.1016/j.msard.2014.01.001.

    Article  PubMed  Google Scholar 

  43. François A, Low SA, Sypek EI, Christensen AJ, Sotoudeh C, Beier KT, et al. A brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and enkephalins. Neuron. 2017;93:822-39.e6. https://doi.org/10.1016/j.neuron.2017.01.008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Max MB, Hagen NA. Do changes in brain sodium channels cause central pain? Neurology. 2000;54:544–5. https://doi.org/10.1212/wnl.54.3.544.

    Article  CAS  PubMed  Google Scholar 

  45. Truini A, Galeotti F, Cruccu G. Treating pain in multiple sclerosis. Expert Opin Pharmacother. 2011;12:2355–68. https://doi.org/10.1517/14656566.2011.607162.

    Article  CAS  PubMed  Google Scholar 

  46. Nefedov OO, Kalbus OI. Mechanisms of occurrence and chronicity of neuropathic pain in multiple sclerosis in clinical and experimental conditions. Ukr Med J. 2022;147–148:7–11. https://doi.org/10.32471/umj.1680-3051.147.226789.

    Article  Google Scholar 

  47. Morales Y, Parisi JE, Lucchinetti CF. The pathology of multiple sclerosis: evidence for heterogeneity. Adv Neurol. 2006;98:27–45.

    PubMed  Google Scholar 

  48. Quiton RL, Masri R, Thompson SM, Keller A. Abnormal activity of primary somatosensory cortex in central pain syndrome. J Neurophysiol. 2010;104:1717–25. https://doi.org/10.1152/jn.00161.2010.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Khare S, Seth D. Lhermitte’s sign: the current status. Ann Indian Acad Neurol. 2015;18:154. https://doi.org/10.4103/0972-2327.150622.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Sá MJ. Physiopathology of symptoms and signs in multiple sclerosis. Arq Neuropsiquiatr. 2012;70:733–40. https://doi.org/10.1590/S0004-282X2012000900016.

    Article  PubMed  Google Scholar 

  51. Al-Araji AH, Oger J. Reappraisal of Lhermitte’s sign in multiple sclerosis. Mult Scler J. 2005;11:398–402. https://doi.org/10.1191/1352458505ms1177oa.

    Article  Google Scholar 

  52. Zhang L, Berta T, Xu Z-Z, Liu T, Park JY, Ji R-R. TNF-alpha contributes to spinal cord synaptic plasticity and inflammatory pain: distinct role of TNF receptor subtypes 1 and 2. Pain. 2011;152:419–27. https://doi.org/10.1016/j.pain.2010.11.014.

    Article  CAS  PubMed  Google Scholar 

  53. Cruccu G, Finnerup NB, Jensen TS, Scholz J, Sindou M, Svensson P, et al. Trigeminal neuralgia. Neurology. 2016;87:220–8. https://doi.org/10.1212/WNL.0000000000002840.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Di Stefano G, Maarbjerg S, Truini A. Trigeminal neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options. J Headache Pain. 2019;20:20. https://doi.org/10.1186/s10194-019-0969-0.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Peker S, Kurtkaya Ö, Üzün İ, Pamir MN. Microanatomy of the central myelin-peripheral myelin transition zone of the trigeminal nerve. Neurosurgery. 2006;59:354–9. https://doi.org/10.1227/01.NEU.0000223501.27220.69.

    Article  PubMed  Google Scholar 

  56. Cruccu G, Biasiotta A, Di Rezze S, Fiorelli M, Galeotti F, Innocenti P, et al. Trigeminal neuralgia and pain related to multiple sclerosis. Pain. 2009;143:186–91. https://doi.org/10.1016/j.pain.2008.12.026.

    Article  CAS  PubMed  Google Scholar 

  57. Godazandeh K, Martinez Sosa S, Wu J, Zakrzewska JM. Trigeminal neuralgia: comparison of characteristics and impact in patients with or without multiple sclerosis. Mult Scler Relat Disord. 2019;34:41–6. https://doi.org/10.1016/j.msard.2019.06.015.

    Article  PubMed  Google Scholar 

  58. Truini A, Prosperini L, Calistri V, Fiorelli M, Pozzilli C, Millefiorini E, et al. A dual concurrent mechanism explains trigeminal neuralgia in patients with multiple sclerosis. Neurology. 2016;86:2094–9. https://doi.org/10.1212/WNL.0000000000002720.

    Article  PubMed  Google Scholar 

  59. Gerwin R. Chronic facial pain: trigeminal neuralgia, persistent idiopathic facial pain, and myofascial pain syndrome: an evidence-based narrative review and etiological hypothesis. Int J Environ Res Public Health. 2020;17:7012. https://doi.org/10.3390/ijerph17197012.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Obermann M, Yoon M-S, Ese D, Maschke M, Kaube H, Diener H-C, et al. Impaired trigeminal nociceptive processing in patients with trigeminal neuralgia. Neurology. 2007;69:835–41. https://doi.org/10.1212/01.wnl.0000269670.30045.6b.

    Article  CAS  PubMed  Google Scholar 

  61. Truini A, Garcia-Larrea L, Cruccu G. Reappraising neuropathic pain in humans—how symptoms help disclose mechanisms. Nat Rev Neurol. 2013;9:572–82. https://doi.org/10.1038/nrneurol.2013.180.

    Article  CAS  PubMed  Google Scholar 

  62. Maarbjerg S, Gozalov A, Olesen J, Bendtsen L. Concomitant persistent pain in classical trigeminal neuralgia: evidence for different subtypes. Headache J Head Face Pain. 2014;54:1173–83. https://doi.org/10.1111/head.12384.

    Article  Google Scholar 

  63. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38:1–211. https://doi.org/10.1177/0333102417738202.

  64. Benoliel R, Svensson P, Evers S, Wang S-J, Barke A, Korwisi B, et al. The IASP classification of chronic pain for ICD-11: chronic secondary headache or orofacial pain. Pain. 2019;160:60–8. https://doi.org/10.1097/j.pain.0000000000001435.

    Article  PubMed  Google Scholar 

  65. Zakrzewska JM. Multi-dimensionality of chronic pain of the oral cavity and face. J Headache Pain. 2013;14:37. https://doi.org/10.1186/1129-2377-14-37.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Cruccu G, Gronseth G, Alksne J, Argoff C, Brainin M, Burchiel K, et al. AAN-EFNS guidelines on trigeminal neuralgia management. Eur J Neurol. 2008;15:1013–28. https://doi.org/10.1111/j.1468-1331.2008.02185.x.

    Article  CAS  PubMed  Google Scholar 

  67. Mazhari A. Multiple sclerosis-related pain syndromes: an imaging update. Curr Pain Headache Rep. 2016;20:63. https://doi.org/10.1007/s11916-016-0594-4.

    Article  PubMed  Google Scholar 

  68. Ferraro D, Plantone D, Morselli F, Dallari G, Simone AM, Vitetta F, et al. Systematic assessment and characterization of chronic pain in multiple sclerosis patients. Neurol Sci. 2018;39:445–53. https://doi.org/10.1007/s10072-017-3217-x.

    Article  PubMed  Google Scholar 

  69. Rog D, Nurmikko T, Young C. Oromucosal Δ9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther. 2007;29:2068–79. https://doi.org/10.1016/j.clinthera.2007.09.013.

    Article  CAS  PubMed  Google Scholar 

  70. Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008;9:506–21. https://doi.org/10.1016/j.jpain.2007.12.010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14:136–48. https://doi.org/10.1016/j.jpain.2012.10.009.

    Article  CAS  PubMed  Google Scholar 

  72. Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 2004;329:253. https://doi.org/10.1136/bmj.38149.566979.AE.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Smith C, Birnbaum G, Carter JL, Greenstein J, Lublin FD. Tizanidine treatment of spasticity caused by multiple sclerosis: results of a double-blind, placebo-controlled trial. US Tizanidine Study Group. Neurology. 1994;44:S34–42 (discussion S42–3).

  74. Vakhapova V, Auriel E, Karni A. Nightly sublingual tizanidine HCl in multiple sclerosis. Clin Neuropharmacol. 2010;33:151–4. https://doi.org/10.1097/WNF.0b013e3181daad7d.

    Article  CAS  PubMed  Google Scholar 

  75. Sachais BA. Baclofen, a new antispastic drug. Arch Neurol. 1977;34:422. https://doi.org/10.1001/archneur.1977.00500190056008.

    Article  CAS  PubMed  Google Scholar 

  76. From A, Heltberg A. A double-blind trial with baclofen (Lioresal®) and diazepam in spasticity due to multiple sclerosis. Acta Neurol Scand. 2009;51:158–66. https://doi.org/10.1111/j.1600-0404.1975.tb01366.x.

    Article  Google Scholar 

  77. Cartlidge NEF, Hudgson P, Weightman D. A comparison of baclofen and diazepam in the treatment of spasticity. J Neurol Sci. 1974;23:17–24. https://doi.org/10.1016/0022-510X(74)90137-3.

    Article  CAS  PubMed  Google Scholar 

  78. Cutter NC, Scott DD, Johnson JC, Whiteneck G. Gabapentin effect on spasticity in multiple sclerosis: a placebo-controlled, randomized trial. Arch Phys Med Rehabil. 2000;81:164–9. https://doi.org/10.1016/s0003-9993(00)90135-7.

    Article  CAS  PubMed  Google Scholar 

  79. Bennett MI, Simpson KH. Gabapentin in the treatment of neuropathic pain. Palliat Med. 2004;18:5–11. https://doi.org/10.1191/0269216304pm845ra.

    Article  PubMed  Google Scholar 

  80. McCleane GJ. Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blinded, placebo-controlled, crossover study. Anesth Analg. 1999;89:985. https://doi.org/10.1097/00000539-199910000-00030.

    Article  CAS  PubMed  Google Scholar 

  81. Harke H, Gretenkort P, Ladleif HU, Rahman S, Harke O. The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Anesth Analg. 2001. https://doi.org/10.1097/00000539-200102000-00039.

    Article  PubMed  Google Scholar 

  82. Cianchetti C, Zuddas A, Randazzo AP, Perra L, Marrosu MG. Lamotrigine adjunctive therapy in painful phenomena in MS: preliminary observations. Neurology. 1999;53:433. https://doi.org/10.1212/WNL.53.2.433.

    Article  CAS  PubMed  Google Scholar 

  83. Vollmer TL, Robinson MJ, Risser RC, Malcolm SK. A randomized, double-blind, placebo-controlled trial of duloxetine for the treatment of pain in patients with multiple sclerosis. Pain Pract. 2014;14:732–44. https://doi.org/10.1111/papr.12127.

    Article  PubMed  Google Scholar 

  84. Aiyer R, Barkin RL, Bhatia A. Treatment of neuropathic pain with venlafaxine: a systematic review. Pain Med. 2016. https://doi.org/10.1093/pm/pnw261.

    Article  Google Scholar 

  85. Vrethem M, Boivie J, Arnqvist H, Holmgren H, Lindström T, Thorell L-H. A comparison of amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. Clin J Pain. 1997;13:313–23. https://doi.org/10.1097/00002508-199712000-00009.

    Article  CAS  PubMed  Google Scholar 

  86. Wang H-Y, Frankfurt M, Burns LH. High-affinity naloxone binding to filamin A prevents mu opioid receptor–Gs coupling underlying opioid tolerance and dependence. PLoS ONE. 2008;3: e1554. https://doi.org/10.1371/journal.pone.0001554.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  87. Cree BAC, Kornyeyeva E, Goodin DS. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. 2010. https://doi.org/10.1002/ana.22006.

    Article  PubMed  Google Scholar 

  88. Gironi M, Martinelli-Boneschi F, Sacerdote P, Solaro C, Zaffaroni M, Cavarretta R, et al. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler J. 2008;14:1076–83. https://doi.org/10.1177/1352458508095828.

    Article  CAS  Google Scholar 

  89. Hyman N. Botulinum toxin (Dysport(R)) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study. J Neurol Neurosurg Psychiatry. 2000;68:707–12. https://doi.org/10.1136/jnnp.68.6.707.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–73. https://doi.org/10.1016/S1474-4422(14)70251-0.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Attal N. Pharmacological treatments of neuropathic pain: the latest recommendations. Rev Neurol (Paris). 2019;175:46–50. https://doi.org/10.1016/j.neurol.2018.08.005.

    Article  CAS  PubMed  Google Scholar 

  92. Sansone RA, Sansone LA. Pain, pain, go away: antidepressants and pain management. Psychiatry (Edgmont). 2008;5:16–9.

    PubMed  Google Scholar 

  93. Liampas A, Rekatsina M, Vadalouca A, Paladini A, Varrassi G, Zis P. Pharmacological management of painful peripheral neuropathies: a systematic review. Pain Ther. 2021;10:55–68. https://doi.org/10.1007/s40122-020-00210-3.

    Article  PubMed  Google Scholar 

  94. Stamoula E, Siafis S, Dardalas I, Ainatzoglou A, Matsas A, Athanasiadis T, et al. Antidepressants on multiple sclerosis: a review of in vitro and in vivo models. Front Immunol. 2021;12: 677879. https://doi.org/10.3389/fimmu.2021.677879.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67:674–94. https://doi.org/10.1111/jgs.15767

  96. Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dubner R. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med. 1992;326:1250–6. https://doi.org/10.1056/NEJM199205073261904.

    Article  CAS  PubMed  Google Scholar 

  97. Sindrup SH, Gram LF, Brøsen K, Eshøj O, Mogensen EF. The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms. Pain. 1990;42:135–44. https://doi.org/10.1016/0304-3959(90)91157-E.

    Article  PubMed  Google Scholar 

  98. Colombo B, Annovazzi POL, Comi G. Medications for neuropathic pain: current trends. Neurol Sci. 2006;27:s183–9. https://doi.org/10.1007/s10072-006-0598-7.

    Article  PubMed  Google Scholar 

  99. Foley P, Parker RA, de Angelis F, Connick P, Chandran S, Young C, et al. Efficacy of fluoxetine, riluzole and amiloride in treating neuropathic pain associated with secondary progressive multiple sclerosis: pre-specified analysis of the MS-SMART double-blind randomised placebo-controlled trial. Mult Scler Relat Disord. 2022;63: 103925. https://doi.org/10.1016/j.msard.2022.103925.

    Article  CAS  PubMed  Google Scholar 

  100. Falah M, Madsen C, Holbech JV, Sindrup SH. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis. Eur J Pain. 2012;16:860–9. https://doi.org/10.1002/j.1532-2149.2011.00073.x.

    Article  CAS  PubMed  Google Scholar 

  101. Jensen TS. Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain. 2002;6:61–8. https://doi.org/10.1053/eujp.2001.0324.

    Article  CAS  PubMed  Google Scholar 

  102. McCleane GJ. Lamotrigine in the management of neuropathic pain: a review of the literature. Clin J Pain. 2000;16:321–6. https://doi.org/10.1097/00002508-200012000-00008.

    Article  CAS  PubMed  Google Scholar 

  103. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118:289–305. https://doi.org/10.1016/j.pain.2005.08.013.

    Article  CAS  PubMed  Google Scholar 

  104. Kim PS, Fishman MA. Low-dose naltrexone for chronic pain: update and systemic review. Curr Pain Headache Rep. 2020;24:64. https://doi.org/10.1007/s11916-020-00898-0.

    Article  PubMed  Google Scholar 

  105. Sharafaddinzadeh N, Moghtaderi A, Kashipazha D, Majdinasab N, Shalbafan B. The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial. Mult Scler J. 2010;16:964–9. https://doi.org/10.1177/1352458510366857.

    Article  CAS  Google Scholar 

  106. Kaiman S, Österberg A, Sörensen J, Boivie J, Bertler Å. Morphine responsiveness in a group of well-defined multiple sclerosis patients: a study with i.v. morphine. Eur J Pain 2002;6:69–80. https://doi.org/10.1053/eujp.2001.0307.

  107. Dworsky-Fried Z, Chadwick CI, Kerr BJ, Taylor AMW. Multiple sclerosis and the endogenous opioid system. Front Neurosci. 2021;15: 741503. https://doi.org/10.3389/fnins.2021.741503.

    Article  PubMed Central  PubMed  Google Scholar 

  108. Marrie RA, Fisk JD, Walld R, Bolton JM, Sareen J, Patten SB, et al. Prescription opioid use in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2023;94:167–9. https://doi.org/10.1136/jnnp-2022-329508.

    Article  PubMed  Google Scholar 

  109. Campos RMP, Aguiar AFL, Paes-Colli Y, Trindade PMP, Ferreira BK, de Melo Reis RA, et al. Cannabinoid therapeutics in chronic neuropathic pain: from animal research to Human treatment. Front Physiol. 2021;12: 785176. https://doi.org/10.3389/fphys.2021.785176.

    Article  PubMed Central  PubMed  Google Scholar 

  110. Anand U, Pacchetti B, Anand P, Sodergren MH. Cannabis-based medicines and pain: a review of potential synergistic and entourage effects. Pain Manag. 2021;11:395–403. https://doi.org/10.2217/pmt-2020-0110.

    Article  PubMed  Google Scholar 

  111. Aborode AT, Awuah WA, Mikhailova T, Abdul- Rahman T, Pavlock S, Nansubuga EP, et al. OMICs Ttchnologies for natural compounds-based drug development. Curr Top Med Chem. 2022;22:1751–65. https://doi.org/10.2174/1568026622666220726092034.

    Article  CAS  PubMed  Google Scholar 

  112. Rudroff T, Sosnoff J. Cannabidiol to improve mobility in people with multiple sclerosis. Front Neurol. 2018;9:183. https://doi.org/10.3389/fneur.2018.00183.

    Article  PubMed Central  PubMed  Google Scholar 

  113. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005;65:812–9. https://doi.org/10.1212/01.wnl.0000176753.45410.8b.

    Article  PubMed  Google Scholar 

  114. Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82:1556–63. https://doi.org/10.1212/WNL.0000000000000363.

    Article  PubMed Central  PubMed  Google Scholar 

  115. Turcotte D, Doupe M, Torabi M, Gomori A, Ethans K, Esfahani F, et al. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Pain Med. 2015;16:149–59. https://doi.org/10.1111/pme.12569.

    Article  PubMed  Google Scholar 

  116. Piper BJ, DeKeuster RM, Beals ML, Cobb CM, Burchman CA, Perkinson L, et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. J Psychopharmacol. 2017;31:569–75. https://doi.org/10.1177/0269881117699616.

    Article  PubMed  Google Scholar 

  117. Nielsen S, Germanos R, Weier M, Pollard J, Degenhardt L, Hall W, et al. The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: a systematic review of reviews. Curr Neurol Neurosci Rep. 2018;18:8. https://doi.org/10.1007/s11910-018-0814-x.

    Article  CAS  PubMed  Google Scholar 

  118. Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 2010;70:2409–38. https://doi.org/10.2165/11585260-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  119. Link K, Knowles LM, Alschuler KN, Ehde DM. Characterizing cannabis use in a sample of adults with multiple sclerosis and chronic pain: an observational study. Mult Scler Relat Disord. 2023;75: 104742. https://doi.org/10.1016/j.msard.2023.104742.

    Article  CAS  PubMed  Google Scholar 

  120. Sirbu C-A, Georgescu R, Pleşa FC, Paunescu A, Marilena Ţânţu M, Nicolae AC, et al. Cannabis and cannabinoids in multiple sclerosis: from experimental models to clinical practice: a review. Am J Ther. 2023;30:e220–31. https://doi.org/10.1097/MJT.0000000000001568.

    Article  PubMed  Google Scholar 

  121. Hansen JS, Gustavsen S, Roshanisefat H, Kant M, Biering-Sørensen F, Andersen C, et al. Cannabis-based medicine for neuropathic pain and spasticity: a multicenter, randomized, double-blinded, placebo-controlled trial. Pharmaceuticals. 2023;16:1079. https://doi.org/10.3390/ph16081079.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  122. Otero-Romero S, Sastre-Garriga J, Comi G, Hartung H-P, Soelberg Sørensen P, Thompson AJ, et al. Pharmacological management of spasticity in multiple sclerosis: systematic review and consensus paper. Mult Scler J. 2016;22:1386–96. https://doi.org/10.1177/1352458516643600.

    Article  CAS  Google Scholar 

  123. Di Stefano G, De Stefano G, Di Lionardo A, Cruccu G, Truini A. Pharmacotherapeutic options for managing pain in multiple sclerosis. CNS Drugs. 2020;34:749–61. https://doi.org/10.1007/s40263-020-00731-7.

    Article  PubMed  Google Scholar 

  124. Yu B, Wu K, Xu X, Liu Y, Jiang J. Recent advances in nanoplatforms for the treatment of neuropathic pain. Spinal Cord. 2022;60:594–603. https://doi.org/10.1038/s41393-021-00746-x.

    Article  PubMed  Google Scholar 

  125. Bidve P, Prajapati N, Kalia K, Tekade R, Tiwari V. Emerging role of nanomedicine in the treatment of neuropathic pain. J Drug Target. 2020;28:11–22. https://doi.org/10.1080/1061186X.2019.1587444.

    Article  CAS  PubMed  Google Scholar 

  126. Zhu Y, Yao Y, Kuang R, Chen Z, Du Z, Qu S. Global research trends of nanotechnology for pain management. Front Bioeng Biotechnol. 2023. https://doi.org/10.3389/fbioe.2023.1249667.

    Article  PubMed Central  PubMed  Google Scholar 

  127. Kuthati Y, Navakanth Rao V, Busa P, Tummala S, Davuluri Venkata Naga G, Wong CS. Scope and applications of nanomedicines for the management of neuropathic pain. Mol Pharm. 2020;17:1015–27. https://doi.org/10.1021/acs.molpharmaceut.9b01027.

  128. Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164:1226–32. https://doi.org/10.1016/j.cell.2016.01.043.

    Article  CAS  PubMed  Google Scholar 

  129. Hunter Z, McCarthy DP, Yap WT, Harp CT, Getts DR, Shea LD, et al. A biodegradable nanoparticle platform for the induction of antigen-specific immune tolerance for treatment of autoimmune disease. ACS Nano. 2014;8:2148–60. https://doi.org/10.1021/nn405033r.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  130. Pearson RM, Casey LM, Hughes KR, Wang LZ, North MG, Getts DR, et al. Controlled delivery of single or multiple antigens in tolerogenic nanoparticles using peptide-polymer bioconjugates. Mol Ther. 2017;25:1655–64. https://doi.org/10.1016/j.ymthe.2017.04.015.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  131. Belousov AN, Belousova EY, Lekomtseva YV. Prospects for the application of nanotechnology in the treatment of multiple sclerosis. Int J Clin Med Case Rep. 2023;2:1–8. https://doi.org/10.31579/2834-8664/017.

    Article  Google Scholar 

  132. Yao L, Bojic D, Liu M. Applications and safety of gold nanoparticles as therapeutic devices in clinical trials. J Pharm Anal. 2023;13:960–7. https://doi.org/10.1016/j.jpha.2023.06.001.

    Article  PubMed Central  PubMed  Google Scholar 

  133. Chen ML, Yao L, Boger J, Mercer K, Thompson B, Jiang N. Non-invasive brain stimulation interventions for management of chronic central neuropathic pain: a scoping review protocol. BMJ Open. 2017;7: e016002. https://doi.org/10.1136/bmjopen-2017-016002.

    Article  PubMed Central  PubMed  Google Scholar 

  134. Johnson MI, Walsh DM. Continued uncertainty of TENS’ effectiveness for pain relief. Nat Rev Rheumatol. 2010;6:314–6. https://doi.org/10.1038/nrrheum.2010.77.

    Article  PubMed  Google Scholar 

  135. Kannan P, Bello UM, Winser SJ. Physiotherapy interventions may relieve pain in individuals with central neuropathic pain: a systematic review and meta-analysis of randomised controlled trials. Ther Adv Chronic Dis. 2022;13:204062232210786. https://doi.org/10.1177/20406223221078672.

    Article  Google Scholar 

  136. Sawant A, Dadurka K, Overend T, Kremenchutzky M. Systematic review of efficacy of TENS for management of central pain in people with multiple sclerosis. Mult Scler Relat Disord. 2015;4:219–27. https://doi.org/10.1016/j.msard.2015.03.006.

    Article  PubMed  Google Scholar 

  137. Mokhtari T, Ren Q, Li N, Wang F, Bi Y, Hu L. Transcutaneous electrical nerve stimulation in relieving neuropathic pain: basic mechanisms and clinical applications. Curr Pain Headache Rep. 2020;24:14. https://doi.org/10.1007/s11916-020-0846-1.

    Article  PubMed  Google Scholar 

  138. Katirci Kirmaci Zİ, Adigüzel H, Göğremiş M, Kirmaci YŞ, İnanç Y, Tuncel BD. The effect of transcutaneous electrical nerve stimulation (TENS) and interferential currents (IFC) on pain, functional capacity, and quality of life in patients with multiple sclerosis: a randomized controlled, single-blinded study. Mult Scler Relat Disord. 2023;71: 104541. https://doi.org/10.1016/j.msard.2023.104541.

    Article  PubMed  Google Scholar 

  139. Lefaucheur J-P, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014–2018). Clin Neurophysiol. 2020;131:474–528. https://doi.org/10.1016/j.clinph.2019.11.002.

    Article  PubMed  Google Scholar 

  140. Comi G, Solari A, Leocani L, Centonze D, Otero-Romero S. Italian consensus on treatment of spasticity in multiple sclerosis. Eur J Neurol. 2020;27:445–53. https://doi.org/10.1111/ene.14110.

    Article  CAS  PubMed  Google Scholar 

  141. Aloizou A-M, Pateraki G, Anargyros K, Siokas V, Bakirtzis C, Liampas I, et al. Transcranial magnetic stimulation (TMS) and repetitive TMS in multiple sclerosis. Rev Neurosci. 2021;32:723–36. https://doi.org/10.1515/revneuro-2020-0140.

    Article  PubMed  Google Scholar 

  142. Palm U, Ayache SS, Padberg F, Lefaucheur J-P. Non-invasive brain stimulation therapy in multiple sclerosis: a review of tDCS, rTMS and ECT results. Brain Stimul. 2014;7:849–54. https://doi.org/10.1016/j.brs.2014.09.014.

    Article  PubMed  Google Scholar 

  143. Mori F, Codecà C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, et al. Effects of nodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain. 2010;11:436–42. https://doi.org/10.1016/j.jpain.2009.08.011.

    Article  PubMed  Google Scholar 

  144. Ayache SS, Palm U, Chalah MA, Al-Ani T, Brignol A, Abdellaoui M, et al. Prefrontal tDCS decreases pain in patients with multiple sclerosis. Front Neurosci. 2016;10:147. https://doi.org/10.3389/fnins.2016.00147.

    Article  PubMed Central  PubMed  Google Scholar 

  145. Young J, Zoghi M, Khan F, Galea MP. The effect of transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis: randomized controlled trial. Pain Med. 2020;21:3451–7. https://doi.org/10.1093/pm/pnaa128.

    Article  PubMed  Google Scholar 

  146. Berra E, Bergamaschi R, De Icco R, Dagna C, Perrotta A, Rovaris M, et al. The effects of transcutaneous spinal direct current stimulation on neuropathic pain in multiple sclerosis: clinical and neurophysiological assessment. Front Hum Neurosci. 2019;13:31. https://doi.org/10.3389/fnhum.2019.00031.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  147. Provenzano DA, Williams JR, Jarzabek G, DeRiggi LA, Scott TF. Treatment of neuropathic pain and functional limitations associated with multiple sclerosis using an MRI-compatible spinal cord stimulator: a case report with two year follow-up and literature review. Neuromodulation Technol Neural Interface. 2016;19:406–13. https://doi.org/10.1111/ner.12409.

    Article  Google Scholar 

  148. Lam CM, Monroe BR. Successful treatment of central pain and spasticity in patient with multiple sclerosis with dorsal column, paresthesia-free spinal cord stimulator: a case report. A&A Pract. 2019;12:308–12. https://doi.org/10.1213/XAA.0000000000000918.

    Article  Google Scholar 

  149. Palm U, Chalah MA, Padberg F, Al-Ani T, Abdellaoui M, Sorel M, et al. Effects of transcranial random noise stimulation (tRNS) on affect, pain and attention in multiple sclerosis. Restor Neurol Neurosci. 2016;34:189–99. https://doi.org/10.3233/RNN-150557.

    Article  CAS  PubMed  Google Scholar 

  150. Harries AM, Mitchell RD. Percutaneous glycerol rhizotomy for trigeminal neuralgia: safety and efficacy of repeat procedures. Br J Neurosurg. 2011;25:268–72. https://doi.org/10.3109/02688697.2011.558946.

    Article  PubMed  Google Scholar 

  151. Patwardhan RV, Minagar A, Kelley RE, Nanda A. Neurosurgical treatment of multiple sclerosis. Neurol Res. 2006;28:320–5. https://doi.org/10.1179/016164106X98224.

    Article  PubMed  Google Scholar 

  152. Berk C, Constantoyannis C, Honey CR. The treatment of trigeminal neuralgia in patients with multiple sclerosis using percutaneous radiofrequency rhizotomy. Can J Neurol Sci/J Can Des Sci Neurol. 2003;30:220–3. https://doi.org/10.1017/S0317167100002626.

    Article  Google Scholar 

  153. Mousavi SH, Gehling P, Burchiel KJ. The long-term outcome of radiofrequency ablation in multiple sclerosis-related symptomatic trigeminal neuralgia. Neurosurgery. 2022;90:293–9. https://doi.org/10.1227/NEU.0000000000001817.

    Article  PubMed  Google Scholar 

  154. Martin S, Teo M, Suttner N. The effectiveness of percutaneous balloon compression in the treatment of trigeminal neuralgia in patients with multiple sclerosis. J Neurosurg. 2015;123:1507–11. https://doi.org/10.3171/2014.11.JNS14736.

    Article  PubMed  Google Scholar 

  155. Noorani I, Lodge A, Vajramani G, Sparrow O. The effectiveness of percutaneous balloon compression, thermocoagulation, and glycerol rhizolysis for trigeminal neuralgia in multiple sclerosis. Neurosurgery. 2019;85:E684–92. https://doi.org/10.1093/neuros/nyz103.

    Article  PubMed  Google Scholar 

  156. Hong T, Ding Y, Yao P. Long-term efficacy and complications of radiofrequency thermocoagulation at different temperatures for the treatment of trigeminal neuralgia. Biochem Res Int. 2020;2020:1–10. https://doi.org/10.1155/2020/3854284.

    Article  Google Scholar 

  157. Al Barim B, Lemcke L, Schwake M, Schipmann S, Stummer W. Repetitive percutaneous radiofrequency thermocoagulation for persistent idiopathic facial pain and central neuropathic pain attributed to multiple sclerosis: a retrospective monocentric analysis. Acta Neurochir (Wien). 2020;162:2791–800. https://doi.org/10.1007/s00701-020-04486-4.

    Article  PubMed  Google Scholar 

  158. Bender MT, Pradilla G, Batra S, See AP, James C, Pardo CA, et al. Glycerol rhizotomy and radiofrequency thermocoagulation for trigeminal neuralgia in multiple sclerosis. J Neurosurg. 2013;118:329–36. https://doi.org/10.3171/2012.9.JNS1226.

    Article  CAS  PubMed  Google Scholar 

  159. Texakalidis P, Xenos D, Karras CL, Rosenow JM. Percutaneous surgical approaches in multiple sclerosis-related trigeminal neuralgia: a systematic review and meta-analysis. World Neurosurg. 2021;146:342-50.e1. https://doi.org/10.1016/j.wneu.2020.11.006.

    Article  PubMed  Google Scholar 

  160. Spina A, Nocera G, Boari N, Iannaccone S, Mortini P. Efficacy of Gamma knife radiosurgery in the management of multiple sclerosis-related trigeminal neuralgia: a systematic review and meta-analysis. Neurosurg Rev. 2021;44:3069–77. https://doi.org/10.1007/s10143-021-01507-3.

    Article  PubMed  Google Scholar 

  161. Leduc W, Mathieu D, Adam E, Ferreira R, Iorio-Morin C. Gamma knife stereotactic radiosurgery for trigeminal neuralgia secondary to multiple sclerosis: a case-control study. Neurosurgery. 2023;93:453–61. https://doi.org/10.1227/neu.0000000000002440.

    Article  PubMed  Google Scholar 

  162. Franzini A, Tropeano MP, Olei S, De Robertis M, Rossini Z, Attuati L, et al. Gamma knife radiosurgery for the treatment of trigeminal neuralgia in patients with multiple sclerosis: a single-center retrospective study and literature review. World Neurosurg. 2021;149:e92-100. https://doi.org/10.1016/j.wneu.2021.02.074.

    Article  PubMed  Google Scholar 

  163. Serhan A, Kiwan A, Abushukair H, Yassin A. Deep brain stimulation use in treating multiple sclerosis tremor: a practical approach for meta-analyses. Mult Scler Relat Disord. 2022;58: 103491. https://doi.org/10.1016/j.msard.2022.103491.

    Article  PubMed  Google Scholar 

  164. Pereira EAC, Aziz TZ. Neuropathic pain and deep brain stimulation. Neurotherapeutics. 2014;11:496–507. https://doi.org/10.1007/s13311-014-0278-x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  165. Naranjo C, Del Reguero L, Moratalla G, Hercberg M, Valenzuela M, Failde I. Anxiety, depression and sleep disorders in patients with diabetic neuropathic pain: a systematic review. Expert Rev Neurother. 2019;19:1201–9. https://doi.org/10.1080/14737175.2019.1653760.

    Article  CAS  PubMed  Google Scholar 

  166. Boiko DI, Chopra H, Bilal M, Kydon PV, Herasymenko LO, Rud VO, et al. Schizophrenia and disruption of circadian rhythms: an overview of genetic, metabolic and clinical signs. Schizophr Res. 2024;264:58–70. https://doi.org/10.1016/j.schres.2023.12.002.

    Article  CAS  PubMed  Google Scholar 

  167. Humo M, Lu H, Yalcin I. The molecular neurobiology of chronic pain-induced depression. Cell Tissue Res. 2019;377:21–43. https://doi.org/10.1007/s00441-019-03003-z.

    Article  PubMed  Google Scholar 

  168. Shkodina AD, Zhyvotovska AI, Boiko DI. Sleep and armed conflict: future complications of war in Ukraine. Rev Neurol (Paris). 2022;178:869–71. https://doi.org/10.1016/j.neurol.2022.09.002.

    Article  PubMed  Google Scholar 

  169. Boiko DI, Skrypnikov AM, Shkodina AD, Hasan MM, Ashraf GM, Rahman MH. Circadian rhythm disorder and anxiety as mental health complications in post-COVID-19. Environ Sci Pollut Res. 2022;29:28062–9. https://doi.org/10.1007/s11356-021-18384-4.

    Article  CAS  Google Scholar 

  170. Boiko DI, Shyrai PO, Mats OV, Karpik ZI, Rahman MH, Khan AA, et al. Mental health and sleep disturbances among Ukrainian refugees in the context of Russian-Ukrainian war: a preliminary result from online-survey. Sleep Med. 2024;113:342–8. https://doi.org/10.1016/j.sleep.2023.12.004.

    Article  PubMed  Google Scholar 

  171. Wijma AJ, van Wilgen CP, Meeus M, Nijs J. Clinical biopsychosocial physiotherapy assessment of patients with chronic pain: the first step in pain neuroscience education. Physiother Theory Pract. 2016;32:368–84. https://doi.org/10.1080/09593985.2016.1194651.

    Article  PubMed  Google Scholar 

  172. Boiko DI, Kachur RV, Ajala OM, Bodnar LA, Zhyvotovska LV. Characteristics of anxiety and depressive manifestations in patients with acute myocardial infarction taking into account their personal accentuations. Azerbaijan Med J. 2021;2:25–31. https://doi.org/10.34921/amj.2021.2.004.

    Article  Google Scholar 

  173. Abu Alhaija ES, AlDaikki A, Al-Omairi MK, Al-Khateeb SN. The relationship between personality traits, pain perception and attitude toward orthodontic treatment. Angle Orthod. 2010;80:1141–9. https://doi.org/10.2319/012710-59.1.

    Article  PubMed Central  PubMed  Google Scholar 

  174. Heitmann H, Biberacher V, Tiemann L, Buck D, Loleit V, Selter RC, et al. Prevalence of neuropathic pain in early multiple sclerosis. Mult Scler J. 2016;22:1224–30. https://doi.org/10.1177/1352458515613643.

    Article  Google Scholar 

  175. Delva M, Skoryk K, Delva I. Predictors of neuropathic dysesthetic pain occurrence and chronification in multiple sclerosis (2-year prospective study). Acta Biomed. 2023;94:e2023229. https://doi.org/10.23750/abm.v94i6.14609.

  176. Driscoll MA, Edwards RR, Becker WC, Kaptchuk TJ, Kerns RD. Psychological interventions for the treatment of chronic pain in adults. Psychol Sci Public Interest. 2021;22:52–95. https://doi.org/10.1177/15291006211008157.

    Article  PubMed  Google Scholar 

  177. Li C, Hou W, Ding D, Yang Y, Gu S, Zhu Y. Evidence mapping based on systematic reviews of cognitive behavioral therapy for neuropathic pain. Neural Plast. 2023;2023:2680620. https://doi.org/10.1155/2023/2680620.

    Article  PubMed Central  PubMed  Google Scholar 

  178. Hayes SC. Acceptance and commitment therapy: towards a unified model of behavior change. World Psychiatry. 2019;18:226–7. https://doi.org/10.1002/wps.20626.

    Article  PubMed Central  PubMed  Google Scholar 

  179. Gromisch ES, Kerns RD, Czlapinski R, Beenken B, Otis J, Lo AC, et al. Cognitive behavioral therapy for the management of multiple sclerosis-related pain. Int J MS Care. 2020;22:8–14. https://doi.org/10.7224/1537-2073.2018-023.

    Article  PubMed Central  PubMed  Google Scholar 

  180. Ma T-W, Yuen AS-K, Yang Z. The efficacy of acceptance and commitment therapy for chronic pain. Clin J Pain. 2023;39:147–57. https://doi.org/10.1097/AJP.0000000000001096.

  181. Harrison AM, McCracken LM, Jones K, Norton S, Moss-Morris R. Using mixed methods case-series evaluation in the development of a guided self-management hybrid CBT and ACT intervention for multiple sclerosis pain. Disabil Rehabil. 2017;39:1785–98. https://doi.org/10.1080/09638288.2016.1209580.

    Article  PubMed  Google Scholar 

  182. Sadeghi-Bahmani D, Esmaeili L, Mokhtari F, Sadeghi Bahmani L, Afsharzadeh M, Shaygannejad V, et al. Effects of acceptance and commitment therapy (ACT) and mindfulness-based stress reduction (MBSR) on symptoms and emotional competencies in individuals with multiple sclerosis. Mult Scler Relat Disord. 2022;67: 104029. https://doi.org/10.1016/j.msard.2022.104029.

    Article  PubMed  Google Scholar 

  183. Hadoush H, Alawneh A, Kassab M, Al-Wardat M, Al-Jarrah M. Effectiveness of non-pharmacological rehabilitation interventions in pain management in patients with multiple sclerosis: systematic review and meta-analysis. NeuroRehabilitation. 2022;50:347–65. https://doi.org/10.3233/NRE-210328.

    Article  PubMed  Google Scholar 

  184. Kubsik A, Klimkiewicz P, Klimkiewicz R, Janczewska K, Woldańska-Okońska M. Rehabilitation in multiple sclerosis. Adv Clin Exp Med. 2017;26:709–15. https://doi.org/10.17219/acem/62329.

  185. Amatya B, Khan F, Galea M. Rehabilitation for people with multiple sclerosis: an overview of Cochrane reviews. Cochrane Database Syst Rev. 2019;1:CD012732. https://doi.org/10.1002/14651858.CD012732.pub2.

  186. Halabchi F, Alizadeh Z, Sahraian MA, Abolhasani M. Exercise prescription for patients with multiple sclerosis; potential benefits and practical recommendations. BMC Neurol. 2017;17:185. https://doi.org/10.1186/s12883-017-0960-9.

    Article  PubMed Central  PubMed  Google Scholar 

  187. Hasanpour DA. Influence of yoga and aerobics exercise on fatigue, pain and psychosocial status in patients with multiple sclerosis: a randomized trial. J Sports Med Phys Fitness. 2016;56:1417–22.

    Google Scholar 

  188. Demaneuf T, Aitken Z, Karahalios A, Leong TI, De Livera AM, Jelinek GA, et al. Effectiveness of exercise interventions for pain reduction in people with multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials. Arch Phys Med Rehabil. 2019;100:128–39. https://doi.org/10.1016/j.apmr.2018.08.178.

    Article  PubMed  Google Scholar 

  189. Hughes C, Smyth S, Lowe-Strong A. Reflexology for the treatment of pain in people with multiple sclerosis: a double-blind randomised sham-controlled clinical trial. Mult Scler J. 2009;15:1329–38. https://doi.org/10.1177/1352458509345916.

    Article  CAS  Google Scholar 

  190. Archer KR, Coronado RA, Wegener ST. The role of psychologically informed physical therapy for musculoskeletal pain. Curr Phys Med Rehabil Rep. 2018;6:15–25. https://doi.org/10.1007/s40141-018-0169-x.

    Article  Google Scholar 

  191. Coronado RA, Brintz CE, McKernan LC, Master H, Motzny N, Silva FM, et al. Psychologically informed physical therapy for musculoskeletal pain: current approaches, implications, and future directions from recent randomized trials. Pain Rep. 2020;5: e847. https://doi.org/10.1097/PR9.0000000000000847.

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurological diseases, Poltava State Medical University, Poltava, Ukraine

    Anastasiia D. Shkodina, Viktoriia A. Pinchuk, Kateryna V. Hryn, Anzhelina M. Kryvchun & Mykhailo Yu. Delva

  2. Neuro Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, 8900 N. Kendall Drive, Miami, FL, 33176, USA

    Mainak Bardhan

  3. Department of Biosciences, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, 602105, Tamil Nadu, India

    Hitesh Chopra

  4. New Vision University, Tbilisi, Georgia

    Onyekachi Emmanuel Anyagwa

  5. Department of Psychiatry, Narcology and Medical Psychology, Poltava State Medical University, Poltava, Ukraine

    Dmytro I. Boiko

  6. King George’s Medical University, Lucknow, India

    Vinay Suresh

  7. Rama Medical College Hospital and Research Centre, Hapur, India

    Amogh Verma

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  1. Anastasiia D. Shkodina
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Correspondence to Mainak Bardhan.

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Funding

This work was supported by Poltava State Medical University (research projects Nos. 0120U104165, 0121U108235, 0124U000094).

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Anastasiia D. Shkodina, Hitesh Chopra, Onyekachi Emmanuel Anyagwa , Mainak Bardhan, Viktoriia A. Pinchuk, Kateryna V. Hryn, Anzhelina M. Kryvchun, Dmytro I. Boiko, Vinay Suresh, Amogh Verma, and Mykhailo Yu. Delva have no conflicts of interest that are directly relevant to the content of this article.

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Authors’ contributions

ADS: conceptualization, methodology, writing—original draft, project administration, writing—review and editing; HC: writing—original draft, writing—review and editing; OEA: writing—original draft; MB: conceptualization, methodology, writing—review and editing; VAP: writing—original draft, KVH: writing—original draft; AMK: writing—original draft; DIB: writing—original draft, writing—review and editing; VS: resources, software, supervision, validation, writing—review and editing; AV: visualization, resources, software, validation; MYD: conceptualization, supervision, validation, writing—original draft.

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Shkodina, A.D., Bardhan, M., Chopra, H. et al. Pharmacological and Non-pharmacological Approaches for the Management of Neuropathic Pain in Multiple Sclerosis. CNS Drugs 38, 205–224 (2024). https://doi.org/10.1007/s40263-024-01072-5

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