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Advances in the Understanding and Management of Chronic Pain in Multiple Sclerosis: a Comprehensive Review

  • Neuropathic Pain (A Abd-Elsayed, Section Editor)
  • Published:
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Abstract

Purpose of Review

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system that can lead to severe physical, cognitive, and neurological deficits that often manifest in young adults. Central neuropathic pain is a common presenting symptom, often prompting patients to seek treatment with opioids, NSAIDS, antiepileptics, and antidepressants despite minimal effectiveness and alarming side-effect profiles. Additionally, spasticity occurs in more than 80% of MS patients and is an important consideration for further study in treatment.

Recent Findings

Related to inconsistencies in pain presentation and clinical reporting, current studies continue to investigate clinical patient presentation to define chronic pain characteristics to optimize treatment plans. Although often neuropathic in origin, the complex nature of such pain necessitates a multimodal approach for adequate treatment. While psychiatric comorbidities typically remain unchanged in their severity over time, physical conditions may lead to worsening chronic pain long-term, often due to decreased quality of life. The prevalence of neuropathic pain is ~ 86% in patients with multiple sclerosis and most commonly presents as extremity pain, trigeminal neuralgia, back pain, or headaches.

Summary

As MS symptoms are frequently unremitting and poorly responsive to conventional medical management, recent attention has been given to novel interventions for management of pain. Among these, medicinal cannabis therapy, targeted physical therapy, and neuromodulation offer promising results. In this review, we provide a comprehensive update of the current perspective of MS pathophysiology, symptomatology, and treatment.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J. 2017;19:1–10.

    PubMed  Google Scholar 

  2. Monteleone F, Nicoletti CG, Stampanoni Bassi M, Iezzi E, Buttari F, Furlan R, et al. Nerve growth factor is elevated in the CSF of patients with multiple sclerosis and central neuropathic pain. J Neuroimmunol. 2018;314:89–93.

    Article  CAS  Google Scholar 

  3. Shahrbanian S, Duquette P, Mayo NE. Impairment, disability and fatigue in multiple sclerosis. Casp J Intern Med. 2018;9:244–51.

    Google Scholar 

  4. 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 Neurol Sci. 2018;39:445–53.

    Article  Google Scholar 

  5. Shahrbanian S, Duquette P, Kuspinar A, Mayo NE. Contribution of symptom clusters to multiple sclerosis consequences. Qual Life Res. 2015;24:617–29.

    Article  Google Scholar 

  6. Green R, Cutter G, Friendly M, Kister I. Which symptoms contribute the most to patients’ perception of health in multiple sclerosis? Mult Scler J Exp Transl Clin. 2017;3:205521731772830.

    Google Scholar 

  7. Patejdl R, Zettl UK. Spasticity in multiple sclerosis: contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions. Autoimmun Rev Elsevier BV. 2017;16:925–36.

    Article  CAS  Google Scholar 

  8. Gilmour H, Ramage-Morin PL, Wong SL. Multiple sclerosis: prevalence and impact. Heal Rep. 2018;29:3–8.

    Google Scholar 

  9. Disanto G, Zecca C, MacLachlan S, Sacco R, Handunnetthi L, Meier UC, et al. Prodromal symptoms of multiple sclerosis in primary care. Ann Neurol. 2018;83:1162–73.

    Article  Google Scholar 

  10. Zhang Y, Taylor B V., Simpson S, Blizzard L, van der Mei I. Patient-reported outcomes are worse for progressive-onset multiple sclerosis than relapse-onset multiple sclerosis, particularly early in the disease process. Eur J Neurol. 2018;1–7.

  11. • Solaro C, Gamberini G, Masuccio FG. Depression in multiple sclerosis: epidemiology, aetiology, diagnosis and treatment. CNS Drugs Springer International Publishing. 2018;32:117–33. An important investigation of depression in patients with multiple sclerosis.

    Article  Google Scholar 

  12. Conradsson D, Ytterberg C, von Koch L, Johansson S. Changes in disability in people with multiple sclerosis: a 10-year prospective study. J Neurol. Springer Berlin Heidelberg. 2017;265:119–26.

    Article  Google Scholar 

  13. Kalia LV, OConnor PW. Severity of chronic pain and its relationship to quality of life in multiple sclerosis. Mult Scler J. Sage PublicationsSage CA: Thousand Oaks, CA. 2005;11:322–7.

    Article  Google Scholar 

  14. Crayton HJ, Rossman HS. Managing the symptoms of multiple sclerosis: a multimodal approach. Clin TherElsevier. 2006;28:445–60.

    Article  Google Scholar 

  15. Young J, Amatya B, Galea MP, Khan F. Chronic pain in multiple sclerosis: a 10-year longitudinal study. Scand J Pain No longer published by Elsevier. 2017;16:198–203.

    Article  Google Scholar 

  16. Marrie RA, Hanwell H. General health issues in multiple sclerosis. Contin Lifelong Learn Neurol. 2013;19:1046–57.

    Article  Google Scholar 

  17. Amtmann D, Askew RL, Kim J, Chung H, Ehde DM, Bombardier CH, et al. Pain affects depression through anxiety, fatigue, and sleep in multiple sclerosis. Rehabil Psychol. 2015;60:81–90.

    Article  Google Scholar 

  18. Chwastiak LA, Gibbons LE, Ehde DM, Sullivan M, Bowen JD, Bombardier CH, et al. Fatigue and psychiatric illness in a large community sample of persons with multiple sclerosis. J Psychosom Res. 2005;59:291–8.

    Article  Google Scholar 

  19. Scherder R, Kant N, Wolf ET, Pijnenburg B, Scherder EJ. Psychiatric and physical comorbidities and pain in patients with multiple sclerosis. J Pain Res Dove Press. 2018;11:325–34.

    Article  Google Scholar 

  20. Finan PH, Garland EL. The role of positive affect in pain and its treatment. Clin J Pain. 2015;31:177–87.

    Article  Google Scholar 

  21. • Scherder RJ, Kant N, Wolf ET, Pijnenburg BCM, Scherder EJA. Sensory function and chronic pain in multiple sclerosis. Pain Res Manag Hindawi. 2018;2018:1–9. Differnces of sensory function in patients with MS.

    Article  Google Scholar 

  22. Marck CH, De Livera AM, Weiland TJ, Jelinek PL, Neate SL, Brown CR, et al. Pain in people with multiple sclerosis: associations with modifiable lifestyle factors, fatigue, depression, anxiety, and mental health quality of life. Front Neurol. 2017;8:461.

    Article  Google Scholar 

  23. Arewasikporn A, Turner AP, Alschuler KN, Hughes AJ, Ehde DM. Cognitive and affective mechanisms of pain and fatigue in multiple sclerosis. Health Psychol. 2018;37:544–52.

    Article  Google Scholar 

  24. Senders A, Borgatti A, Hanes D, Shinto L. Association between pain and mindfulness in multiple sclerosis: a cross-sectional survey. Int J MS Care The Consortium of Multiple Sclerosis Centers. 2018;20:28–34.

    Article  Google Scholar 

  25. Mazhari A. Multiple sclerosis-related pain syndromes: an imaging update. Curr Pain Headache Rep Springer US. 2016;20:63.

    Article  Google Scholar 

  26. Hemond CC, Bakshi R. Magnetic resonance imaging in multiple sclerosis. Cold Spring Harb Perspect Med. Cold Spring Harbor Laboratory Press. 2018;8:a028969.

    Article  Google Scholar 

  27. Sigaut S, Merckx P, Peuch C, Necib S, Pingeon F, Mantz J. Does an educational strategy based on systematic preoperative assessment of simplified Apfel’s score decrease postoperative nausea and vomiting? Ann Fr Anesth Reanim. 2010;29:765–9.

    Article  CAS  Google Scholar 

  28. Ploughman M, Beaulieu S, Harris C, Hogan S, Manning OJ, Alderdice PW, et al. The Canadian survey of health, lifestyle and ageing with multiple sclerosis: methodology and initial results. BMJ Open. 2014;4:e005718.

    Article  Google Scholar 

  29. Fallata A, Salter A, Tyry T, Cutter G, Marrie RA. Trigeminal neuralgia commonly precedes the diagnosis of multiple sclerosis. Int J MS Care. 2017;19:240–6.

    Article  Google Scholar 

  30. Zakrzewska J, Wu J, Brathwaite T. A systematic review of the management of trigeminal neuralgia in patients with multiple sclerosis. World Neurosurg. 2018;111:291–306.

    Article  Google Scholar 

  31. Reder A, Amason B. Trigeminal neuralgia in multiple sclerosis relieved by a prostaglandin E analogue. Neurology. 1995;45:1097–100.

    Article  CAS  Google Scholar 

  32. Xu Z, Mathieu D, Heroux F, Abbassy M, Barnett G, Mohammadi A, et al. Stereotactic radiosurgery for trigeminal neuralgia in patients with multiple sclerosis: a multicenter study. Neurosurgery. 2018;0.

  33. Sahai-Srivastava S, Wang SL, Ugurlu C, Amezcua L. Headaches in multiple sclerosis: cross-sectional study of a multiethnic population. Clin Neurol Neurosurg. 2016;143:71–5.

    Article  Google Scholar 

  34. Mantia L, Prone V. Headache in multiple sclerosis and autoimmune disorders. Neurol Sci. 2015;36:S75–8.

    Article  Google Scholar 

  35. Togha M, Khoshsirat NA, Moghadasi AN, Mousavinia F, Mozafari M, Neishaboury M, et al. Headache in relapse and remission phases of multiple sclerosis: a case-control study. Iran J Neurol. 2016;15:1–8.

    PubMed  PubMed Central  Google Scholar 

  36. Husain F, Pardo G, Rabadi M. Headache and its management in patients with multiple sclerosis. Curr Treat Options Neurol. 2018;20:10.

    Article  Google Scholar 

  37. Gebhardt M, Kropp P, Jürgens TP, Hoffmann F, Zettl UK. Headache in the first manifestation of multiple sclerosis – prospective, multicenter study. Brain Behav. 2017;7:e00852.

    Article  Google Scholar 

  38. Gustavsen M, Celius E, Winsvold B, Moen S, Nygaard G, Berg-Hansen P, et al. Migraine and frequent tension-type headache are not associated with multiple sclerosis in a Norwegian case-control study. Mult Scler J Exp Transl Clin. 2016;2:1–4.

    Google Scholar 

  39. Terlizzi R, Merli E, Buccellato E, Giannini G, Favoni V, Pierangeli G, et al. Headache in multiple sclerosis: prevalence and clinical features in a case control-study. J Headache Pain. 2015;16:A83.

    Article  Google Scholar 

  40. Beggs CB, Giaquinta A, Veroux M, De Marco E, Mociskyte D, Veroux P. Mid-term sustained relief from headaches after balloon angioplasty of the internal jugular veins in patients with multiple sclerosis. PLoS One. 2018;13:e0191534.

    Article  Google Scholar 

  41. Murphey KL, Bethea JR, Fischer R. Neuropathic pain in multiple sclerosis—current therapeutic intervention and future treatment perspectives. Mult Scler Perspect Treat Pathog. 2017;53–69.

  42. 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.

    Article  Google Scholar 

  43. Khan A, Kamran S, Ponirakis G, Akhtar N, Khan R, George P, et al. Peripheral neuropathy in patients with multiple sclerosis. PLoS One. 2018.

  44. 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.

    Article  Google Scholar 

  45. Patten DK, Schultz BG, Berlau DJ. The safety and efficacy of low-dose naltrexone in the management of chronic pain and inflammation in multiple sclerosis, fibromyalgia, Crohn’s disease, and other chronic pain disorders. Pharmacotherapy. 2018;38:382–9.

    Article  CAS  Google Scholar 

  46. Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet Elsevier. 2003;362:1517–26.

    Article  CAS  Google Scholar 

  47. Gan TJ, Sinha AC, Kovac AL, Jones RK, Cohen SA, Battikha JP, et al. A randomized, double-blind, multicenter trial comparing transdermal scopolamine plus ondansetron to ondansetron alone for the prevention of postoperative nausea and vomiting in the outpatient setting. Anesth Analg. 2009;108:1498–504.

    Article  CAS  Google Scholar 

  48. Rice J, Cameron M. Cannabinoids for treatment of MS symptoms: state of the evidence. Curr Neurol Neurosci Rep. 2018;18:50.

    Article  Google Scholar 

  49. Rudroff T, Sosnoff J. Cannabidiol to improve mobility in people with multiple sclerosis. Front Neurol Frontiers Media SA. 2018;9:183.

    Article  Google Scholar 

  50. Turri M, Teatini F, Donato F, Zanette G, Tugnoli V, Deotto L, et al. Pain modulation after oromucosal cannabinoid spray (SATIVEX®) in patients with multiple sclerosis: a study with quantitative sensory testing and laser-evoked potentials. Medicines. 2018;5:59.

    Article  CAS  Google Scholar 

  51. Stockings E, Campbell G, Hall WD, Nielsen S, Zagic D, Rahman R, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions. Pain. 2018;159:1932–54.

    Article  CAS  Google Scholar 

  52. 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.

    Article  Google Scholar 

  53. Amato L, Minozzi S, Mitrova Z, Parmelli E, Saulle R, Cruciani F, et al. Systematic review of safeness and therapeutic efficacy of cannabis in patients with multiple sclerosis, neuropathic pain, and in oncological patients treated with chemotherapy. Epidemiol Prev. 41:279–93.

  54. Landa L, Jurica J, Sliva J, Pechackova M, Demlova R. Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice. Biomed Pap. 2018;162:18–25.

    Article  Google Scholar 

  55. Lynch ME, Ware MA. Cannabinoids for the treatment of chronic non-cancer pain: an updated systematic review of randomized controlled trials. J NeuroImmune Pharmacol. 2015;10:293–301.

    Article  CAS  Google Scholar 

  56. Jitpakdee T, Mandee S. Strategies for preventing side effects of systemic opioid in postoperative pediatric patients. 2014.

  57. Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, et al. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Taylor & Francis; 2013. https://doi.org/10.1179/016164109X12590518685660.

    Article  CAS  Google Scholar 

  58. Demaneuf T, Aitken Z, Karahalios A, Leong TI, De Livera A, Jelinek G, et al. The 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. 2018.

  59. Kahraman T, Ozdogar AT, Yigit P, Hosgel I, Mehdiyev Z, Ertekin O, et al. Feasibility of a 6-month yoga program to improve the physical and psychosocial status of persons with multiple sclerosis and their family members. Explore. 2018;14:36–43.

    Article  Google Scholar 

  60. Halabchi F, Alizadeh Z, Sahraian M, Abolhasani M. Exercise prescription for patients with multiple sclerosis; potential benefits and practical recommendations. BioMed Cent Neurol. 2017;17.

  61. Motl R, Sandroff B, Kwakkel G, Dalgas U, Feinstein A, Heesen C, et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017;16:848–56.

    Article  Google Scholar 

  62. Ryan J, Fortune J, Stennett A, Kilbride C, Anokye N, Victor C, et al. Changing physical activity behaviour for people with multiple sclerosis: protocol of a randomised controlled feasibility trial (iStep-MS). Br Med J Open. 2017;7.

  63. Rimmer J, Thirumalai M, Young H, Pekmezi D, Tracy T, Riser E, et al. Rationale and design of the tele-exercise and multiple sclerosis (TEAMS) study: a comparative effectiveness trial between a clinic- and home-based telerehabilitation intervention for adults with multiple sclerosis (MS) living in the deep south. Contemp Clin Trials. 2018;71:186–93.

    Article  Google Scholar 

  64. Abboud H, Hill E, Siddiqui J, Serra A, Walter B. Neuromodulation in multiple sclerosis. Mult Scler. 2017;23:1663–76.

    Article  Google Scholar 

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Authors and Affiliations

  1. Beth Israel Deaconess Medical Center, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA

    Ivan Urits

  2. Creighton University School of Medicine, Phoenix Regional Campus, Phoenix, AZ, USA

    Leena Adamian, Jacob Fiocchi & Dylan Hoyt

  3. A T Still University, Kirksville College Of Osteopathic Medicine, Kirksville, MO, USA

    Carly Ernst

  4. Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Alan D. Kaye

  5. Valley Anesthesiology and Pain Consultants, Phoenix, AZ, USA

    Omar Viswanath

  6. Department of Anesthesiology, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA

    Omar Viswanath

  7. Department of Anesthesiology, Creighton University School of Medicine, Omaha, NE, USA

    Omar Viswanath

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  1. Ivan Urits
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Correspondence to Ivan Urits.

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Conflict of Interest

Ivan Urits, Leena Adamian, Jacob Fiocchi, Dylan Hoyt, Carly Ernst, and Omar Viswanath declare no conflict of interest. Alan D. Kaye discloses that he is on the Speakers Bureau for Depomed, Inc. and Merck.

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Urits, I., Adamian, L., Fiocchi, J. et al. Advances in the Understanding and Management of Chronic Pain in Multiple Sclerosis: a Comprehensive Review. Curr Pain Headache Rep 23, 59 (2019). https://doi.org/10.1007/s11916-019-0800-2

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