Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Management of pain in multiple sclerosis: a pharmacological approach

Abstract

About half of patients with multiple sclerosis (MS) report pain; treatment for pain alone accounts for nearly 30% of the total use of medications for the management of all MS-related symptoms. Patients with MS can experience more than one type of pain simultaneously and at any point during the disease course, even in newly or recently diagnosed cases. Pain in MS can be associated with other symptoms, including spasticity, fatigue and mood disorder. Pain sufferers experience disruption in daily life activities, work, mood, recreation and general enjoyment of life, and report low satisfaction with pain management. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. The majority of clinical evidence regarding treatment stems from small pilot and open-label studies; therefore, treatment of pain associated with MS is often based on anecdotal reports and clinicians' experience. The open-label design of the majority of studies, the unavailability of large samples and the difficulty of performing placebo-controlled studies because of ethical considerations result in insufficient evidence to support or refute the effectiveness of pain medications. This Review presents available data regarding pharmacological approaches for addressing pain in MS and highlights the shortcomings in pain management research.

Key Points

  • Pain syndromes are common in individuals with multiple sclerosis (MS), even early in the disease, and differentiating neuropathic from non-neuropathic pain is difficult

  • Pain treatment in MS requires vigilance; patients can experience more than one type of pain, necessitating multiple pharmacological interventions, which can cause compounded adverse events, including clinical worsening of MS

  • Literature on pain management is lacking, particularly reports of randomized clinical trials, and clinicians often rely on experience and anecdotal reports for deciding treatment regimens

  • Although potentially effective for treating some types of pain in MS, tricyclic antidepressants and antiepileptic medications have notable adverse events, which often prohibits use of these drugs to their full potential

  • Correct identification and effective management of pain are crucial, as pain can markedly influence quality of life, including, among others, everyday activities, work and mood

  • Progress in the area of pain associated with MS will depend on the development of multiple-arm, randomized clinical trials to determine optimal treatment strategies

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Paty, D. W. & Ebers, G. C. in Multiple Sclerosis 135–191 (F. A. Davis Company, Philadelphia, 1999).

    Google Scholar 

  2. Brichetto, G., Messmer Uccelli, M., Mancardi, G. L. & Solaro, C. Symptomatic medication use in multiple sclerosis. Mult. Scler. 9, 458–460 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Hadjimichael, O., Kerns, R. D., Rizzo, M. A., Cutter, G. & Vollmer, T. Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain 127, 35–41 (2007).

    Article  PubMed  Google Scholar 

  4. Clifford, D. B. & Trotter, J. L. Pain in multiple sclerosis. Arch. Neurol. 41, 1270–1272 (1984).

    Article  CAS  PubMed  Google Scholar 

  5. Vermote, R., Ketalaer, P. & Carlton, H. Pain in multiple sclerosis patients: a prospective study using the McGill pain questionnaire. Clin. Neurol. Neurosurg. 88, 87–93 (1986).

    Article  CAS  PubMed  Google Scholar 

  6. Kassirer, M. R. & Osterberg, D. H. Pain in chronic multiple sclerosis. J. Pain Symptom Manage. 2, 95–97 (1987).

    Article  CAS  PubMed  Google Scholar 

  7. Moulin, D. E., Foley, K. M. & Ebers, G. C. Pain syndromes in multiple sclerosis. Neurology 38, 1830–1834 (1988).

    Article  CAS  PubMed  Google Scholar 

  8. Stenager, E., Knutsen, L. & Jensen, K. Acute and chronic pain syndromes in multiple sclerosis. Acta Neurol. Scand. 84, 197–200 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Warnell, P. The pain experience of a multiple sclerosis population: a descriptive study. Axon 13, 26–28 (1991).

    CAS  PubMed  Google Scholar 

  10. Archibald, C. J. et al. Pain prevalence, severity and impact in a clinical sample of multiple sclerosis patients. Pain 58, 89–93 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Indaco, A., Iachetta, C., Nappi. C., Socci, L. & Carrieri, P. B. Chronic and acute pain syndromes in patients with multiple sclerosis. Acta Neurol. 16, 97–102 (1994).

    CAS  Google Scholar 

  12. Stenager, E., Knudsen, L. & Jensen, K. Acute and chronic pain syndromes in multiple sclerosis. Ital. J. Neurol. Sci. 16, 629–632 (1995).

    Article  CAS  PubMed  Google Scholar 

  13. Beiske, A. G., Pedersen, E. D., Czujko, B. & Myhr, K. M. Pain and sensory complaints in multiple sclerosis. Eur. J. Neurol. 1, 479–482 (2004).

    Article  Google Scholar 

  14. Ehde, D. M. et al. Chronic pain in a large community sample of persons with multiple sclerosis. Mult. Scler. 6, 605–611 (2003).

    Article  Google Scholar 

  15. Svendsen, K. B. et al. Pain in patients with multiple sclerosis: a population-based study. Arch. Neurol. 60, 1089–1094 (2003).

    Article  PubMed  Google Scholar 

  16. Solaro, C. et al. The prevalence of pain in multiple sclerosis. A multicenter cross-sectional study. Neurology 63, 919–921 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Österberg, A., Boivie, J. & Thomas, K. A. Central pain in multiple sclerosis-prevalence and clinical characteristics. Eur. J. Pain 9, 531–542 (2005).

    Article  PubMed  Google Scholar 

  18. Ehde, D. M., Osborne, T. L., Hanley, M. A., Jensen, M. P. & Kraft, G. H. The scope and nature of pain in persons with multiple sclerosis. Mult. Scler. 12, 629–638 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Piwko, C. et al. Pain due to multiple sclerosis: analysis of the prevalence and economic burden in Canada. Pain Res. Manag. 12, 259–265 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Khan, F. & Pallant, J. Chronic pain in multiple sclerosis: prevalence, characteristics and impact on quality of life in an Australian community cohort. J. Pain 8, 614–623 (2007).

    Article  PubMed  Google Scholar 

  21. Boneschi, M. et al. Lifetime and actual prevalence of pain and headache in multiple sclerosis. Mult Scler. 14, 514–521 (2008).

    Article  Google Scholar 

  22. Douglas, C., Wollin, J. & Windsor, C. Illness and demographic correlates of chronic pain among a community-based sample of people with multiple sclerosis. Arch. Phys. Med. Rehabil. 89, 1923–1932 (2008).

    Article  PubMed  Google Scholar 

  23. Hirsh, A. T., Turner, A. P., Ehde, D. M. & Haselkorn, J. K. Prevalence and impact of pain in multiple sclerosis: physical and psychological contributors. Arch. Phys. Med. Rehabil. 90, 646–651 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Moses, H. & Brandes, D. W. Managing adverse effects of disease-modifying agents used for treatment of multiple sclerosis. Curr. Med. Res. Opin. 24, 2679–2690 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Cohen, B. A., Greenberg, P. A. & Saini, S. Delayed occurrence of a severe cutaneous reaction in a multiple sclerosis patient taking interferon beta-1b. Allergy Asthma Proc. 19, 85–88 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Calabresi, P. A. Considerations in the treatment of relapsing–remitting multiple sclerosis. Neurology 58 (Suppl. 4), S10–S22 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Walther, E. U. & Hohlfeld, R. Multiple sclerosis side effects of interferon beta therapy and their management. Neurology. 53, 1622–1627 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Galer, B. S. & Jensen, M. P. Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain Scale. Neurology 48, 332–338 (1997).

    Article  CAS  PubMed  Google Scholar 

  29. Grasso, M. G. et al. Pain in multiple sclerosis: a clinical and instrumental approach. Mult. Scler. 14, 506–513 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. Forbes, A., While, A., Mathes, L. & Griffiths, P. Health problems and health-related quality of life in people with multiple sclerosis. Clin. Rehabil. 20, 67–78 (2006).

    Article  PubMed  Google Scholar 

  31. Kalia, L. V. & O'Connor, P. W. Severity of chronic pain and its relationship to quality of life in multiple sclerosis. Mult. Scler. 11, 322–327 (2005).

    Article  PubMed  Google Scholar 

  32. Svendsen, K. B., Jensen, T. S., Hansen, H. J. & Bach, F. W. Sensory function and quality of life in patients with multiple sclerosis and pain. Pain 114, 473–481 (2005).

    Article  PubMed  Google Scholar 

  33. Brochet, B. et al. Pain and quality of life in the early stages after multiple sclerosis diagnosis: a 2-year longitudinal study. Clin. J. Pain. 25, 211–217 (2009).

    Article  PubMed  Google Scholar 

  34. Motl, R. W. & McAuley, E. Symptom cluster as a predictor of physical activity in multiple sclerosis: preliminary evidence. J. Pain Symptom Manage. 38, 270–280 (2009).

    Article  PubMed  Google Scholar 

  35. Aicher, S. A., Silverman, M. B., Winkler, C. W. & Bebo, B. F. Hyperalgesia in an animal model of multiple sclerosis. Pain 58, 89–93 (2004).

    Google Scholar 

  36. Olechowski, C. J., Troung, J. J. & Kerr, B. J. Neuropathic pain behaviours in a chronic–relapsing model of experimental autoimmune encephalomyelitis. Pain 141, 156–164. (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Lynch, J., Gallus, N., Ericson, M. & Beitz, A. Analysis of nociception, sex and peripheral nerve innervations in the TMEV animal model of multiple sclerosis. Pain 136, 293–304 (2008).

    Article  PubMed  Google Scholar 

  38. Saarto, T. & Wiffen, P. J. Antidepressants for neuropathic pain. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD005454 doi:10.1002/14651858.CD005454.pub2 (2007).

  39. Solaro, C., Brichetto, G., Battaglia, M. A., Messmer Uccelli, M. & Mancardi, G. L. Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study. Neurol. Sci. 25, 307–310 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Killian, J. M. & Fromm, G. H. Carbamazepine in the treatment of neuralgia: use and side effects. Arch. Neurol. 19, 129–136 (2001).

    Article  Google Scholar 

  41. Cianchetti, C., Zuddas, A., Randazzo, A. P., Perra, L. & Marrosu, M. G. Lamotrigine adjunctive therapy in painful phenomena in MS: preliminary observations. Neurology 53, 433 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Breuer, B. et al. Randomized double-blind, placebo-controlled two period crossover pilot trial of lamotrigine in patients with central pain due to multiple sclerosis. Clin. Ther. 29, 2022–2030 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Houtchens, M. K., Richert, J. R., Sami, A. & Rose, J. W. Open label gabapentin treatment for pain in multiple sclerosis. Mult. Scler. 3, 250–253 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. Rossi, S. et al. Effects of Levetiracetam on chronic pain in multiple sclerosis: results of a randomized placebo-controlled study. Eur. J. Neurol. 16, 360–366 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Solaro, C., Boemker, M. & Tanganelli, P. Pregabalin for treating paroxysmal symptoms in multiple sclerosis: a pilot study. J. Neurol. 256, 1773–1774 (2009).

    Article  PubMed  Google Scholar 

  46. Solaro, C. & Tanganelli, P. Acute delirium in patients with multiple sclerosis treated with pregabalin. Clin. Neuropharmacol. 32, 236–237 (2009).

    Article  PubMed  Google Scholar 

  47. Dario, A. & Tomei, G. Management of spasticity in multiple sclerosis by intrathecal baclofen. Acta Neurochir. Suppl. 97, 189–192 (2007).

    CAS  PubMed  Google Scholar 

  48. Herman, R. M., D'Luzansky, S. C. & Ippolito, R. Intrathecal baclofen suppresses central pain in patients with spinal lesions. A pilot study. Clin. J. Pain. 8, 338–345 (1992).

    Article  CAS  PubMed  Google Scholar 

  49. Sadiq, S. & Poopatana, C. Intrathecal basclofen and morphine in multiple sclerosis patients with severe pain and spasticity. J. Neurol. 254, 1464–1465 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Kalman, S., Österberg, A., Sörensen, J., Boivie, J. & Bertler, A. Morphine responsiveness in a group of well-defined multiple sclerosis patients: a study with i.v. morphine. Eur. J. Pain. 6, 69–80 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Sakurai, M. & Kanazawa, I. Positive symptoms in multiple sclerosis: their treatment with sodium channel blockers, lidocaine and mexiletine. J. Neurol. Sci. 162, 162–168 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Svendsen, K. B., Jensen, T. S. & Bach, F. W. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ 329, 253 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Solari, A. Role of health-related quality of life measures in the routine care of people with multiple sclerosis. Health Qual. Life Outcomes 18, 16 (2005).

    Article  Google Scholar 

  54. Rog, D. J., Nurmikko, T. J. & Young, C. A. Oromucosal delta9-tetrahydrocannabinol/ cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin. Ther. 29, 2068–2079 (2007).

    Article  CAS  PubMed  Google Scholar 

  55. Zajicek, J. et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 362, 1517–1526 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Wade, D. T., Makela, P., Robson, P., House, H. & Bateman, C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult. Scler. 10, 434–441 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Putzki, N. et al. Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis. Eur. J. Neurol. 16, 262–267 (2009).

    Article  CAS  PubMed  Google Scholar 

  58. Hooge, J. P. & Redekop, W. K. Trigeminal neuralgia in multiple sclerosis. Neurology 45, 1294–1296 (1995).

    Article  CAS  PubMed  Google Scholar 

  59. Jensen, T. S., Rasmussen, P. & Reske-Nielsen, E. Association of trigeminal neuralgia with multiple sclerosis: clinical and pathological features. Acta Neurol. Scand. 65, 182–189 (1982).

    Article  CAS  PubMed  Google Scholar 

  60. Love, S. & Coakham, H. B. Trigeminal neuralgia: pathology and pathogenesis. Brain 124, 2347–2360 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Mills, R. J., Young, C. A. & Smith, E. T. Central trigeminal involvement in multiple sclerosis using high-resolution MRI at 3T. Br. J. Radiol. 83, 493–498 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Cruccu, G. et al. Trigeminal neuralgia and pain related to multiple sclerosis. Pain 143, 186–191 (2009).

    Article  CAS  PubMed  Google Scholar 

  63. Hutchins, L. G., Harnsberger, H. R., Jacobs, J. M. & Apfelbaum, R. I. Trigeminal neuralgia (tic douloureux): MR imaging assessment. Radiology 175, 837–841 (1990).

    Article  CAS  PubMed  Google Scholar 

  64. Espir, M. L. & Millac, P. Treatment of paroxysmal disorders in multiple sclerosis with carbamazepine (Tegretol). J. Neurol. Neurosurg. Psychiatry 33, 528–531 (1970).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Solaro, C., Uccelli, M. M., Uccelli, A., Leandri, M. & Mancardi, G. L. Low-dose gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis. Eur. Neurol. 44, 45–48 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Ramsaransing, G., Zwanikken, C. & De Keyser, J. Worsening of symptoms of multiple sclerosis associated with carbamazepine. BMJ 320, 1113 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Leandri, M. et al. Lamotrigine in trigeminal neuralgia secondary to multiple sclerosis. J. Neurol. 247, 556–558 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Lunardi, G. et al. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology 48, 1714–1717 (1997).

    Article  CAS  PubMed  Google Scholar 

  69. Khan, O. A. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients. Neurology 51, 611–614 (1998).

    Article  CAS  PubMed  Google Scholar 

  70. Solaro, C. et al. An open-label trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients. Neurology 51, 609–611 (1998).

    Article  CAS  PubMed  Google Scholar 

  71. Zvartau-Hind, M., Din, M. U., Gilani, A., Lisak, R. P. & Khan, O. A. Topiramate relieves refractory trigeminal neuralgia in MS patients. Neurology 55, 1587–1588 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Solaro, C., Uccelli, M. M., Brichetto, G., Gasperini, C. & Mancardi, G. L. Topiramate relieves idiopathic and symptomatic trigeminal neuralgia. J. Pain Symptom Manage. 21, 367–368 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Reder, A. T. & Arnason, B. Trigeminal neuralgia in multiple sclerosis relieved by a prostaglandin E analogue. Neurology 45, 1097–1100 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. DMKG study group. Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis. J. Neurol. 250, 542–545 (2003).

  75. Attal, N. et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur. J. Neurol. 17, 1113–e88 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Linderoth, B. & Hakanson, S. Paroxysmal facial pain in disseminated sclerosis treated by retrogasserian glycerol injection. Acta Neurol. Scand. 80, 341–346 (1989).

    Article  CAS  PubMed  Google Scholar 

  77. Kondziolka, D., Lunsford, L. D. & Bissonette, D. J. Long-term results after glycerol rhizotomy for multiple sclerosis-related trigeminal neuralgia. Can. J. Neurol. Sci. 21, 137–140 (1994).

    Article  CAS  PubMed  Google Scholar 

  78. Berk, C., Constantoyannis, C. & Honey, C. R. The treatment of trigeminal neuralgia in patients with multiple sclerosis using percutaneous radiofrequency rhizotomy. Can. J. Neurol. Sci. 30, 220–223 (2003).

    Article  PubMed  Google Scholar 

  79. Broggi, G. & Franzini, A. Radiofrequency trigeminal rhizotomy in treatment of symptomatic non-neoplastic facial pain. J. Neurosurg. 57, 483–486 (1982).

    Article  CAS  PubMed  Google Scholar 

  80. Rogers, C. L. et al. Gamma knife radiosurgery for trigeminal neuralgia associated with multiple sclerosis. J. Neurosurg. 97 (Suppl. 5), 529–532 (2002).

    Article  PubMed  Google Scholar 

  81. Huang, E. et al. Gamma knife radiosurgery for treatment of trigeminal neuralgia in multiple sclerosis patients. Stereotact. Funct. Neurosurg. 79, 44–50 (2002).

    Article  PubMed  Google Scholar 

  82. Athanasiou, T. C., Patel, N. K., Renowden, S. A. & Coakham, H. B. Some patients with multiple sclerosis have neurovascular compression causing their trigeminal neuralgia and can be treated effectively with MVD: report of five cases. Br. J. Neurosurg. 19, 463–468 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Meaney, J. F. M. et al. Association between trigeminal neuralgia and multiple sclerosis: role of magnetic resonance imaging. J. Neurol. Neurosurg. Psychiatry. 59, 253–259 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Broggi, G. et al. Role of microvascular decompression in trigeminal neuralgia and multiple sclerosis. Lancet 354, 1878–1879 (1999).

    Article  CAS  PubMed  Google Scholar 

  85. Broggi, G., Ferroli, P., Franzini, A., Servello, D. & Dones, I. Microvascular decompression for trigeminal nevralgia: comments on a series of 250 cases, including 10 with multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 68, 59–64 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kanner, R. M. in Multiple Sclerosis Therapeutics (eds Rudick, R. & Goodkin, D) 542 (Martin Dunitz, London, 1999).

    Google Scholar 

  87. Al-Araji, A. H. & Oger, J. Reappraisal of Lhermitte's sign in multiple sclerosis. Mult. Scler. 11, 398–402 (2005).

    Article  PubMed  Google Scholar 

  88. Minagar, A. & Sheremata, W. A. Glossopharyngeal neuralgia and MS. Neurology 54, 1368–1370 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Halper, J. in Nursing Practice in Multiple Sclerosis: a Core Curriculum 2nd edn (eds Halper, J. et al.) 129–132 (Demos Medical Publishing, New York, 2006).

    Google Scholar 

  90. O'Connor, A. B., Schwid, S. R., Herrmann, D. N., Markman, J. D. & Dworkin, R. H. Pain associated with multiple sclerosis: systematic review and proposed classification. Pain 137, 96–111 (2008).

    Article  PubMed  Google Scholar 

  91. Solaro, C., Uccelli, M. M., Guglieri, P., Uccelli, A. & Mancardi, G. L. Gabapentin is effective in treating nocturnal painful spasms in multiple sclerosis. Mult. Scler. 6, 192–193 (2000).

    Article  CAS  PubMed  Google Scholar 

  92. Solaro, C. & Tanganelli, P. Tiagabine for treating painful tonic spasms in multiple sclerosis: a pilot study. J. Neurol. Neurosurg. Psychiatry 75, 341 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Restivo, D. A., Tinazzi, M., Patti, F., Palmeri, A. & Maimone, D. Botulinum toxin treatment of painful tonic spasms in multiple sclerosis. Neurology 61, 719–720 (2003).

    Article  CAS  PubMed  Google Scholar 

  94. Thompson, A. J. Symptomatic treatment in multiple sclerosis. Curr. Opin. Neurol. 11, 305–309 (1998).

    Article  CAS  PubMed  Google Scholar 

  95. Nicoletti, A. et al. Headache and multiple sclerosis: a population-based case–control study in Catania, Sicily. Cephalalgia 28, 1163–1169 (2008).

    Article  CAS  PubMed  Google Scholar 

  96. Vacca, G. et al. Multiple sclerosis and headache co-morbidity. A case–control study. Neurol. Sci. 28, 133–135 (2007).

    Article  CAS  PubMed  Google Scholar 

  97. Rolak, L. A. & Brown, S. Headaches and multiple sclerosis: a clinical study and review of the literature. J. Neurol. 237, 300–302 (1990).

    Article  CAS  PubMed  Google Scholar 

  98. Gee, J. R., Chang, J., Dublin, A. B. & Vijayan, N. The association of brainstem lesions with migraine-like headache: an imaging study of multiple sclerosis. Headache 45, 670–677 (2005).

    Article  PubMed  Google Scholar 

  99. Tortorella, P. et al. Assessment of MRI abnormalities of the brainstem from patients with migraine and multiple sclerosis. J. Neurol. Sci. 244, 137–141 (2006).

    Article  PubMed  Google Scholar 

  100. Villani, V. et al. Primary headache and multiple sclerosis: preliminary results of a prospective study. Neurol. Sci. 29, S146–S148 (2008).

    Article  PubMed  Google Scholar 

  101. Duncan, C. W., Watson, D. P. B. & Stein, A. Guideline Development Group. Diagnosis and management of headache in adults: summary of SIGN guideline. BMJ 337, a2329 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. La Mantia, L. Headache and multiple sclerosis: clinical and therapeutic correlations. Neurol. Sci. 30, S23–S26 (2009).

    Article  PubMed  Google Scholar 

  103. Pöllmann, W., Erasmus, L. P., Feneberg, W., Then Bergh, F. T. & Straube, A. Interferon beta but not glatiramer acetate therapy aggravates headache in MS. Neurology 59, 636–639 (2002).

    Article  PubMed  Google Scholar 

  104. Stuifbergen, A. K., Becker, H., Blozis, S., Timmerman, G. & Kullberg, V. A randomized clinical trial of a wellness intervention for women with multiple sclerosis. Arch. Phys. Med. Rehabil. 84, 467–476 (2003).

    Article  PubMed  Google Scholar 

  105. Stude, D. E. & Mick, T. Clinical presentation of patient with MS and response to manual chiropractic adjustive therapies. J. Manipulative Physiol. Ther. 16, 595–600 (1993).

    CAS  PubMed  Google Scholar 

  106. Vardy, T. C. Enhancing homeostasis using osteopathic techniques for multiple sclerosis. Aust. J. Osteopath. 8, 20–26 (1997).

    Google Scholar 

  107. Yates, H. A., Vardy, T. C., Kuchera, M. L., Ripley, B. D. & Johnson, J. C. Effects of osteopathic manipulative treatment and concentric and eccentric maximal effort exercise on women with multiple sclerosis: a pilot study. J. Am. Osteopathic Assoc. 102, 267–275 (2002).

    Google Scholar 

  108. Mills, N. & Allen, J. Mindfulness of movement as a coping strategy in multiple sclerosis. A pilot study. Gen. Hosp. Psychiatry 22, 425–431 (2000).

    Article  CAS  PubMed  Google Scholar 

  109. Lienau, F. S., Füllgraf, H., Moser, A. & Feuerstein, T. J. Why do cannabinoids not show consistent effects as analgesic drugs in multiple sclerosis? Eur. J. Neurol. 14, 1162–1169 (2007).

    Article  CAS  PubMed  Google Scholar 

  110. Marrie, R. A., Horwitz, R. I., Cutter, G., Tyry, T. & Vollmer, T. Association between comorbidity and clinical characteristics of MS. Acta Neurol. Scand. 29, 135–141 (2010).

    Google Scholar 

  111. Haythornthwaite, J. A. & Benrud-Larsen, L. M. Psychological aspects of neuropathic pain. Clin. J. Pain. 16, S101–S105 (2000).

    Article  CAS  PubMed  Google Scholar 

  112. Duarte, R. in Pain Management Secrets (ed. Kanner, R.) 6 (Hanley & Belfus, Philadelphia, 2003).

    Google Scholar 

  113. Farrar, J. T. Advances in clinical research methodology for pain clinical trials. Nat. Med. 16, 1284–1293 (2010).

    Article  CAS  PubMed  Google Scholar 

  114. Grond, S. et al. Assessment and treatment of neuropathic cancer pain following WHO guidelines. Pain 79, 15–20 (1999).

    Article  CAS  PubMed  Google Scholar 

  115. Treede, R. D. et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 70, 1630–1635 (2008).

    Article  CAS  PubMed  Google Scholar 

  116. Wewers, M. E. & Lowe, N. K. A critical review of visual analogue scales in the measurement of clinical phenomena. Res. Nurs. Health 13, 227–236 (1990).

    Article  CAS  PubMed  Google Scholar 

  117. Osborne, T. L., Raichle, K. A., Jensen, M. P., Ehde, D. M. & Kraft, G. The reliability and validity of pain interference measures in persons with multiple sclerosis. J. Pain Symptom Manage. 32, 217–229 (2006).

    Article  PubMed  Google Scholar 

  118. Rog, D. J., Nurmikko, T. J., Friede, T. & Young, C. A. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 65, 812–819 (2005).

    Article  PubMed  Google Scholar 

  119. Granger, C. V. Clinical measures of disability in multiple sclerosis patients. Neurol. Sci. 25, S353–S354 (2004).

    Google Scholar 

  120. Langley, G. B. & Shepperd, H. The visual analogue scale: its use in pain measurement. Rheumatol. Int. 5, 145–148 (1985).

    Article  CAS  PubMed  Google Scholar 

  121. Rog, D. J., Nurmikko, T. J., Friede, T. & Young, C. A. Validation and reliability of the Neuropathic Pain Scale (NPS) in multiple sclerosis. Clin. J. Pain. 23, 473–481 (2007).

    Article  PubMed  Google Scholar 

  122. Fischer, J. S. et al. Recent developments in the assessment of quality of life in multiple sclerosis. Mult. Scler. 5, 251–259 (1999).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the Italian Multiple Sclerosis Society and S. Minguzzi, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy, for support in preparing this Review.

Author information

Authors and Affiliations

Authors

Contributions

Both authors contributed equally to researching, discussing, writing, reviewing and editing this manuscript.

Corresponding author

Correspondence to Claudio Solaro.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Solaro, C., Messmer Uccelli, M. Management of pain in multiple sclerosis: a pharmacological approach. Nat Rev Neurol 7, 519–527 (2011). https://doi.org/10.1038/nrneurol.2011.120

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2011.120

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing