Skip to main content
Log in

Current Management of Pain Associated with Multiple Sclerosis

  • Review Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

While pain is a common problem in patients with multiple sclerosis (MS), it is not frequently mentioned by patients and a more direct approach is required in order to obtain information about pain from patients. Many patients with MS experience more than one pain syndrome; combinations of dysaesthesia, headaches and/or back or muscle and joint pain are frequent. For each pain syndrome a clear diagnosis and therapeutic concept needs to be established.

Pain in MS can be classified into four diagnostically and therapeutically relevant categories: (i) neuropathic pain due to MS (pain directly related to MS); (ii) pain indirectly related to MS; (iii) MS treatment-related pain; and (iv) pain unrelated to MS.

Painful paroxysmal symptoms such as trigeminal neuralgia (TN), or painful tonic spasms are treated with antiepileptics as first choice, e.g. carbamazepine, oxcarbazepine, lamotrigine, gabapentin, pregabalin, etc. Painful ‘burning’ dysaes-thesias, the most frequent chronic pain syndrome, are treated with TCAs such as amitriptyline, or antiepileptics such as gabapentin, pregabalin, lamotrigine, etc. Combinations of drugs with different modes of action can be particularly useful for reducing adverse effects. While escalation therapy may require opioids, there are encouraging results from studies regarding cannabinoids, but their future role in the treatment of MS-related pain has still to be determined.

Pain related to spasticity often improves with adequate physiotherapy. Drug treatment includes antispastic agents such as baclofen or tizanidine and in patients with phasic spasticity, gabapentin or levetiracetam are administered. In patients with severe spasticity, botulinum toxin injections or intrathecal baclofen merit consideration. While physiotherapy may ameliorate malposition-induced joint and muscle pain, additional drug treatment with paracetamol (acetaminophen) or NSAIDs may be useful. Moreover, painful pressure lesions should be avoided by using optimally adjusted aids.

Treatment-related pain associated with MS can occur with subcutaneous injections of interferon-β or glatiramer acetate, and may be reduced by optimizing the injection technique and by local cooling. Systemic (particularly ‘flu-like’) adverse effects of interferons, e.g. myalgias, can be reduced by administering paracetamol, ibuprofen or naproxen. A potential increase in the frequency of preexisting headaches after starting treatment with interferons may require optimization of headache attack therapy or even prophylactic treatment.

Pain unrelated to MS, such as back pain or headache, is common in patients with MS and may deteriorate as a result of the disease.

In summary, a careful analysis of each pain syndrome will allow the design of the appropriate treatment plan using various medical and nonmedical options (multimodal therapy), and will thus help to improve the quality of life (QOL) of the patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Table I
Table II
Table III
Table IV
Table V
Table VI
Table VII
Table VIII
Table IX
Table X
Table XI
Fig. 2

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Ehde DM, Gibbons LE, Chwastiak L, et al. Chronic pain in a large community sample of persons with multiple sclerosis. Mult Scler 2003; 9: 605–11

    Article  PubMed  Google Scholar 

  2. Stenager E, Knudsen L, Jensen K. Acute and chronic pain syndromes in multiple sclerosis: a 5-year follow-up study. Ital J Neurol Sci 1995; 16: 629–32

    Article  PubMed  CAS  Google Scholar 

  3. Stenager E, Knudsen L, Jensen K. Acute and chronic pain syndromes in multiple sclerosis. Acta Neurol Scand 1991; 84: 197–200

    Article  PubMed  CAS  Google Scholar 

  4. Osterberg A, Boivie J, Thuomas KA. Central pain in multiple sclerosis: prevalence and clinical characteristics. Eur J Pain 2005; 9(5): 531–42

    Article  PubMed  CAS  Google Scholar 

  5. Beiske AG, Pedersen ED, Czujko B, et al. Pain and sensory complaints in multiple sclerosis. Eur J Neurol 2004; 11(7): 479–82

    Article  PubMed  CAS  Google Scholar 

  6. Ehde DM, Osborne TL, Hanley MA, et al. The scope and nature of pain in persons with multiple sclerosis. Mult Scler 2006; 12(5): 629–38

    Article  PubMed  CAS  Google Scholar 

  7. Hadjimichael O, Kerns RD, Rizzo MA, et al. Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain 2007; 127(1-2): 35–41

    Article  PubMed  Google Scholar 

  8. Solaro C, Brichetto G, Amato MP, et al. The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study. PaIMS Study Group. Neurology 2004; 63(5): 919–21

    CAS  Google Scholar 

  9. Pöllmann W, Feneberg W, Erasmus L-P. Pain in multiple sclerosis: a still underestimated problem. The 1-year prevalence of pain syndromes, significance and quality of care of multiple sclerosis inpatients [in German]. Nervenarzt 2004; 75(2): 135–40

    Article  PubMed  Google Scholar 

  10. Solomon P. Congruence between health professionals’ and patients’ pain ratings: a review of the literature. Scand J Caring Sci 2001; 15: 174–80

    Article  PubMed  CAS  Google Scholar 

  11. Marchettini P, Formaglio F, Lacerenza M. Pain as heralding symptom in multiple sclerosis. Neurol Sci 2006; 27Suppl. 4: S294–6

    Article  Google Scholar 

  12. Merskey H, Bogduk N, editors. Classification of chronic pain. 2nd ed. Seattle (WA): IASP Press, 1994

    Google Scholar 

  13. Headache Classification Committee of the International Headache Society. The international classification of headache disorders. 2nd ed. Cephalalgia 2004; 24Suppl. 1: 1–160

    Google Scholar 

  14. Beard S, Hunn A, Wight J. Treatments for spasticity and pain in multiple sclerosis: a systematic review. Health Technol Assess 2003; 7: 1–124

    Google Scholar 

  15. Attal N, Cruccu G, Haanpaa M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. EFNS Task Force. Eur J Neurol 2006; 13(11): 1153–69

    Article  PubMed  CAS  Google Scholar 

  16. Rog DJ, Nurmikko TJ, Friede T, et al. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 2005; 65(6): 812–9

    Article  PubMed  Google Scholar 

  17. Sindrup SH, Jensen TS. Effect of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999; 83: 389–400

    Article  PubMed  CAS  Google Scholar 

  18. Sindrup SH, Jensen TS. Pharmacologie treatment of pain in polyneuropathy. Neurology 2000; 55: 915–20

    Article  PubMed  CAS  Google Scholar 

  19. Sindrup SH, Jensen TS. Pharmacotherapy of trigeminal neuralgia. Clin J Pain 2002; 18: 22–7

    Article  PubMed  Google Scholar 

  20. Kalia LV, O’Connor PW. Severity of chronic pain and its relationship to quality of life in multiple sclerosis. Mult Scler 2005; 11(3): 322–7

    Article  PubMed  Google Scholar 

  21. Khan F, Pallant J. Chronic pain in multiple sclerosis: prevalence, characteristics, and impact on quality of life in an Australian community cohort. J Pain 2007 Aug; 8(8): 614–23

    Article  PubMed  Google Scholar 

  22. Fleming WE, Pollak CP. Sleep disorders in multiple sclerosis. Semin Neurol 2005 Mar; 25(1): 64–8

    Article  PubMed  Google Scholar 

  23. Ehde DM, Osborne TL, Jensen MP. Chronic pain in persons with multiple sclerosis. Phys Med Rehabil Clin N Am 2005 May; 16(2): 503–12

    Article  PubMed  Google Scholar 

  24. Osborne TL, Jensen MP, Ehde DM, et al. Psychosocial factors associated with pain intensity, pain-related interference, and psychological functioning in persons with multiple sclerosis and pain. Pain 2007 Jan; 127(1-2): 52–62

    Article  PubMed  Google Scholar 

  25. Cleeland CS. The brief pain inventory. Pain Research Group. Copyright 1991, Dr Charles Cleeland, Anderson Cancer Center, Pain Research Group, 1100 Holcombe, Houston, TX 77030 (additional information available in: Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore 1994; 23(2): 129–38)

    CAS  Google Scholar 

  26. Melzack R. The McGill pain questionnaire: major properties and scoring methods. Pain 1975 Sep; 1(3): 277–99

    Article  PubMed  CAS  Google Scholar 

  27. Heckman-Stone C, Stone C. Pain management techniques used by patients with multiple sclerosis. J Pain 2001 Aug; 2(4): 205–8

    Article  PubMed  CAS  Google Scholar 

  28. Higginson IJ, Hart S, Silber E, et al. Symptom prevalence and severity in people severely affected by multiple sclerosis. J Palliat Care 2006; 22(3): 158–65

    PubMed  Google Scholar 

  29. Kümpfel T, Hoffmann LA, Pöllmann W, et al. Palliative care in patients with severe multiple sclerosis: two case reports and a survey among German MS neurologists. Palliat Med 2007 Mar; 21(2): 109–14

    Article  PubMed  Google Scholar 

  30. Young WF, Weaver M, Mishra B. Surgical outcome in patients with coexisting multiple sclerosis and spondylosis. Acta Neurol Scand 1999; 100: 84–7

    Article  PubMed  CAS  Google Scholar 

  31. Bashir K, Cai CY, Moore TA, et al. Surgery for cervical spinal cord compression in patients with multiple sclerosis. Neurosurgery 2000; 47: 637–42

    PubMed  CAS  Google Scholar 

  32. Etus V, Akansel G, Ilbay K, et al. Multiple sclerosis and coexisting intradural extramedullary spinal cord tumor: a case report. Neurol Sci 2002; 23: 119–22

    Article  PubMed  CAS  Google Scholar 

  33. Goodin DS, Frohman EM, Garmany GP, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002; 58: 169–78

    Article  PubMed  CAS  Google Scholar 

  34. Pöllmann W, Feneberg W, Steinbrecher A, et al. Therapy of pain syndromes in multiple sclerosis: an overview with evidence-based recommendations [in German]. Fortschr Neurol Psychiatr 2005; 73(5): 268–85

    Article  PubMed  Google Scholar 

  35. Feneberg W. Neurogenic bowel dysfunction: In: Henze T, Rieckmann P, Toyka KV. Symptomatic treatment of multiple sclerosis. Multiple Sclerosis Therapy Consensus Group (MSTCG) of the German Multiple Sclerosis Society. Eur Neurol 2006; 56 (2): 87–8

    Google Scholar 

  36. Optic Neuritis Study Group. The clinical profile of optic neuritis: experience of the Optic Neuritis Treatment Trial. Arch Ophthalmol 1991; 109: 1673–8

    Article  Google Scholar 

  37. Haas DC, Kent PF, Friedman DI. Headache caused by single lesion of multiple sclerosis in the periaqueductal gray area. Headache 1993; 33: 452–5

    Article  PubMed  CAS  Google Scholar 

  38. Feneberg W, Pöllmann W. Headache in multiple sclerosis: a prospective study using the IHS classification criteria [abstract]. J Neurol 2000; 247Suppl. 3: III/179

    Google Scholar 

  39. Pöllmann W, Mayr B, ten Bruggencate G, et al. Cervicogenic headache in multiple sclerosis with cervical spinal demyelination: coincidental or causal? Akt Neurol 2005; 32: 445–50

    Article  Google Scholar 

  40. Sellebjerg F, Barnes D, Filippini G, et al. EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses. Eur J Neurol 2005; 12(12): 939–46

    Article  PubMed  CAS  Google Scholar 

  41. Rieckmann P, Toyka KV, Bassetti C, et al. Escalating immunotherapy of multiple sclerosis: new aspects and practical application. Multiple Sclerosis Therapy Consensus Group. J Neurol 2004; 251(11): 1329–39

    Article  PubMed  CAS  Google Scholar 

  42. Hellwig K, Lukas C, Brune N, et al. Repeat intrathecal triamcinolone acetonide application reduces acute occurring painful dysesthesia in patients with relapsing remitting multiple sclerosis. ScientificWorldJournal 2006; 6: 460–5

    Article  PubMed  CAS  Google Scholar 

  43. Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Neurology 2002; 59Suppl. 2: S14–7

    Article  PubMed  Google Scholar 

  44. Zakrzewska JM, Chaudhry Z, Nurmikko TJ, et al. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain 1997; 73: 223–30

    Article  PubMed  CAS  Google Scholar 

  45. Fromm GH, Terrence CF, Chattha AS. Baclofen in the treatment of trigeminal neuralgia: double-blind study and long-term follow-up. Ann Neurol 1984; 15(3): 240–4

    Article  PubMed  CAS  Google Scholar 

  46. Chandra B. The use of clonazepam in the treatment of tic douloureux (a preliminary report). Proc Aust Assoc Neurol 1976; 13: 119–22

    PubMed  CAS  Google Scholar 

  47. Peiris JB, Perera GL, Devendra SV, et al. Sodium valproate in trigeminal neuralgia [letter]. Med J Aust 1980; 2: 278

    PubMed  CAS  Google Scholar 

  48. Kanai A, Suzuki A, Kobayashi M, et al. Intranasal lidocaine 8% spray for second-division trigeminal neuralgia. Br J Anaesth 2006; 97(4): 559–63

    Article  PubMed  CAS  Google Scholar 

  49. Hooge JP, Redekop WK. Trigeminal neuralgia in multiple sclerosis. Neurology 1995; 45: 1294–6

    Article  PubMed  CAS  Google Scholar 

  50. Solaro C, Lunardi GL, Capello E, et al. An open-label trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients. Neurology 1998; 51: 609–11

    Article  PubMed  CAS  Google Scholar 

  51. Solaro C, Messmer Uccelli M, et al. Low-dose gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis. Eur Neurol 2000; 44: 45–8

    Article  PubMed  CAS  Google Scholar 

  52. Khan OA. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients. Neurology 1998; 51: 611–4

    Article  PubMed  CAS  Google Scholar 

  53. Leandri M, Lundardi G, Inglese M, et al. Lamotrigine in trigeminal neuralgia secondary to multiple sclerosis. J Neurol 2000; 247: 556–8

    Article  PubMed  CAS  Google Scholar 

  54. Lunardi G, Leandri M, Albano C, et al. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology 1997; 48: 1714–7

    Article  PubMed  CAS  Google Scholar 

  55. DMKG Study Group. Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis. J Neurol 2003; 250: 542–5

    Article  CAS  Google Scholar 

  56. Zvartau-Hind M, Din MU, Gilani A, et al. Topiramate relieves refractory trigeminal neuralgia in MS patients. Neurology 2000; 55: 1587–8

    Article  PubMed  CAS  Google Scholar 

  57. D’Aleo G, Sessa E, Di Bella P, et al. Topiramate modulation of R3 nociceptive reflex in multiple sclerosis patients suffering paroxysmal symptoms. J Neurol 2001; 248: 996–9

    Article  PubMed  Google Scholar 

  58. Berk C, Constantoyannis C, Honey CR. The treatment of trigeminal neuralgia in patients with multiple sclerosis using percutaneous radiofrequency rhizotomy. Can J Neurol Sci 2003; 30: 220–3

    PubMed  Google Scholar 

  59. Kondziolka D, Lunsford LD, Bissonette DJ. Long-term results after glycerol rhizotomy for multiple sclerosis-related trigeminal neuralgia. Can J Neurol Sci 1994; 21: 137–40

    PubMed  CAS  Google Scholar 

  60. Pickett GE, Bisnaire D, Ferguson GG. Percutaneous retrogasserian glycerol rhizotomy in the treatment of tic douloureux associated with multiple sclerosis. Neurosurgery 2005 Mar; 56(3): 537–45

    Article  PubMed  Google Scholar 

  61. Broggi G, Ferroli P, Franzini A, et al. Role of microvascular decompression in trigeminal neuralgia and multiple sclerosis. Lancet 1999; 354: 1878–9

    Article  PubMed  CAS  Google Scholar 

  62. Huang E, Teh BS, Zeck O, et al. Gamma knife radiosurgery for treatment of trigeminal neuralgia in multiple sclerosis patients. Stereotact Funct Neurosurg 2002; 79(1): 44–50

    Article  PubMed  Google Scholar 

  63. McCleane G. Pharmacological management of neuropathic pain. CNS Drugs 2003; 17: 1031–43

    Article  PubMed  CAS  Google Scholar 

  64. Wiffen P, Collins S, McQuay H, et al. Anticonvulsant drugs for acute and chronic pain. Cochrane Database Syst Rev 2005 Jul 20; (3): CD001133

  65. Wiffen PJ, McQuay HJ, Moore RA. Carbamazepine for acute and chronic pain. Cochrane Database Syst Rev 2005 Jul 20; (3): CD005451

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

    Article  PubMed  CAS  Google Scholar 

  67. Zakrzewska JM, Patsalos PN. Oxcarbazepine: a new drug in the management of intractable trigeminal neuralgia. J Neurol Neurosurg Psychiatry 1989; 52: 472–6

    Article  PubMed  CAS  Google Scholar 

  68. Carrazana E, Mikoshiba I. Rationale and evidence for the use of oxcarbazepine in neuropathic pain. J Pain Symptom Manage 2003; 25(5 Suppl.): S31–5

    Article  PubMed  CAS  Google Scholar 

  69. Solaro C, Restivo D, Mancardi GL, et al. Oxcarbazepine for treating paroxysmal painful symptoms in multiple sclerosis: a pilot study. Neurol Sci 2007; 28(3): 156–8

    Article  PubMed  CAS  Google Scholar 

  70. Schmidt D, Elger CE. How is oxcarbazepine different from carbamazepine [in German]? Nervenarzt 2004; 75: 153–60

    Article  PubMed  CAS  Google Scholar 

  71. Beydoun A. Safety and efficacy of oxcarbazepine: results of randomized, double-blind trials. Pharmacotherapy 2000; 20 (8 Pt 2): 152–8S

    Article  Google Scholar 

  72. Solaro C, Brichetto G, Battaglia MA, et al. Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study. Neurol Sci 2005; 25(6): 307–10

    Article  PubMed  CAS  Google Scholar 

  73. Obermann M, Yoon MS, Sensen K, et al. Efficacy of pregabalin in the treatment of trigeminal neuralgia. Cephalalgia 2008; 28(2): 174–81

    PubMed  CAS  Google Scholar 

  74. Lüttmann RJ, Brinkmann B, Loddenkemper T, et al. Misoprostol in the treatment of trigeminal neuralgia in MS patients: a report of three cases [abstract]. Cephalalgia 2000; 20: 382

    Google Scholar 

  75. Reder AT, Arnason BG. Trigeminal neuralgia in multiple sclerosis relieved by a prostaglandin E analogue. Neurology 1995; 45: 1097–100

    Article  PubMed  CAS  Google Scholar 

  76. Solaro C, Uccelli MM, Brichetto G, et al. Topiramate relieves idiopathic and symptomatic trigeminal neuralgia. J Pain Symptom Manage 2001; 21: 367–8

    Article  PubMed  CAS  Google Scholar 

  77. Gilron I, Booher SL, Rowan JS, et al. Topiramate in trigeminal neuralgia: a randomized, placebo-controlled multiple crossover pilot study. Clin Neuropharmacol 2001; 24: 109–12

    Article  PubMed  CAS  Google Scholar 

  78. Lechin F, van der Dijs B, Lechin ME, et al. Pimozide therapy for trigeminal neuralgia. Arch Neurol 1989; 46: 960–3

    Article  PubMed  CAS  Google Scholar 

  79. Piovesan EJ, Teive HG, Kowacs PA, et al. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 2005; 65(8): 1306–8

    Article  PubMed  CAS  Google Scholar 

  80. Parmar BS, Shah KH, Gandhi IC. Baclofen in trigeminal neuralgia: a clinical trial. Indian J Dent Res 1989; 1: 109–13

    PubMed  CAS  Google Scholar 

  81. Steardo L, Leo A, Marano E. Efficacy of baclofen in trigeminal neuralgia and some other painful conditions: a clinical trial. Eur Neurol 1984; 23: 51–5

    Article  PubMed  CAS  Google Scholar 

  82. Fusco BM, Alessandri M. Analgesic effect of capsaicin in idiopathic trigeminal neuralgia. Anesth Analg 1992; 74: 375–7

    Article  PubMed  CAS  Google Scholar 

  83. Broggi G, Ferroli P, Franzini A, et al. Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2000; 68: 59–64

    Article  PubMed  CAS  Google Scholar 

  84. Broggi G, Ferroli P, Franzini A, et al. Operative findings and outcomes of microvascular decompression for trigeminal neuralgia in 35 patients affected by multiple sclerosis. Neurosurgery 2004; 55(4): 830–8, discussion 838-9

    Article  PubMed  Google Scholar 

  85. Athanasiou TC, Patel NK, Renowden SA, et al. 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 2005; 19(6): 463–8

    Article  PubMed  CAS  Google Scholar 

  86. Kondziolka D, Lunsford L, Flickinger J. Stereotactic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain 2002; 18: 42–7

    Article  PubMed  Google Scholar 

  87. Lim M, Villavicencio AT, Burneikiene S, et al. CyberKnife radiosurgery for idiopathic trigeminal neuralgia. Neurosurg Focus 2005 May 15; 18(5): E9

    Article  PubMed  Google Scholar 

  88. Henson CF, Goldman HW, Rosenwasser RH, et al. Glycerol rhizotomy versus gamma knife radiosurgery for the treatment of trigeminal neuralgia: an analysis of patients treated at one institution. Int J Radiat Oncol Biol Phys 2005; 63(1): 82–90

    Article  PubMed  Google Scholar 

  89. Cheng JS, Sanchez-Mejia RO, Limbo M, et al. Management of medically refractory trigeminal neuralgia in patients with multiple sclerosis. Neurosurg Focus 2005; 18(5): E13

    Article  PubMed  Google Scholar 

  90. Minagar A, Sheremata WA. Glossopharyngeal neuralgia and MS. Neurology 2000; 54: 1368–70

    Article  PubMed  CAS  Google Scholar 

  91. Garcia-Callejo FJ, Velert-Vila MM, Talamantes-Escriba F, et al. Clinical response of gabapentin for glossopharyngeal neuralgia [in Spanish]. Rev Neurol 1999; 28(4): 380–4

    PubMed  CAS  Google Scholar 

  92. Guido M, Specchio LM. Glossopharyngeal neuralgia responding to pregabalin. Headache 2006; 46(8): 1307–8

    Article  PubMed  Google Scholar 

  93. Espir ML, Millac P. Treatment of paroxysmal disorders in multiple sclerosis with carbamazepine (Tegretol). J Neurol Neurosurg Psychiatry 1970; 33: 528–31

    Article  PubMed  CAS  Google Scholar 

  94. Twomey JA, Espir MLE. Paroxysmal symptoms as the first manifestations of multiple sclerosis. J Neurol Neurosurg Psychiatry 1980; 43: 296–304

    Article  PubMed  CAS  Google Scholar 

  95. Cianchetti C, Zuddas A, Randazzo AP, et al. Lamotrigine adjunctive therapy in painful phenomena in MS: preliminary observations. Neurology 1999; 53: 433

    Article  PubMed  CAS  Google Scholar 

  96. Voiculescu V, Pruskauer-Apostol B, Alecu C. Treatment with acetazolamide of brain-stem and spinal paroxysmal disturbances in multiple sclerosis. J Neurol Neurosurg Psychiatry 1975; 38: 191–3

    Article  PubMed  CAS  Google Scholar 

  97. Blakeley J, Jankovic J. Secondary paroxysmal dyskinesias. Mov Disord 2002; 17: 726–34

    Article  PubMed  Google Scholar 

  98. Shibasaki H, Kuroiwa Y. Painful tonic seizures in multiple sclerosis. Arch Neurol 1974; 30: 47–51

    Article  PubMed  CAS  Google Scholar 

  99. Spissu A, Cannas A, Ferrigno P, et al. Anatomic correlates of painful tonic spasms in multiple sclerosis. Mov Disord 1999; 14: 331–5

    Article  PubMed  CAS  Google Scholar 

  100. Libenson MH, Stafstrom CE, Rosman NP. Tonic “seizures” in a patient with brainstem demyelination: a MRI study of brain and spinal cord. Pediatr Neurol 1994; 11: 258–62

    Article  PubMed  CAS  Google Scholar 

  101. Kuroiwa Y, Shibasaki H. Painful tonic seizure in multiple sclerosis: treatment with diphenylhydantoin and carbamazepine. Folia Pychiatr Neurol Jap 1968; 22: 107–19

    CAS  Google Scholar 

  102. Sakurai M, Kanazawa I. Positive symptoms in multiple sclerosis: their treatment with sodium channel blockers, lidocaine and mexiletine. J Neurol Sci 1999; 162: 162–8

    Article  PubMed  CAS  Google Scholar 

  103. Okada S, Kinoshita M, Fujioka T, et al. Two cases of multiple sclerosis with painful tonic seizures and dysesthesia ameliorated by the administration of mexiletine. Jpn J Med 1991; 30: 373–5

    Article  PubMed  CAS  Google Scholar 

  104. Galer BS, Harle J, Rowbotham MC. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. J Pain Symptom Manage 1996; 12: 161–7

    Article  PubMed  CAS  Google Scholar 

  105. Solaro C, Tanganelli P. Tiagabine for treating painful tonic spasms in multiple sclerosis: a pilot study [letter]. J Neurol Neurosurg Psychiatry 2004; 75(2): 341

    PubMed  CAS  Google Scholar 

  106. Sethi KD, Hess DC, Huffnagle VH, et al. Acetazolamide treatment of paroxysmal dystonia in central demyelinating disease. Neurology 1992; 42: 919–21

    Article  PubMed  CAS  Google Scholar 

  107. Vermote R, Ketelaer P, Carton H. Pain in multiple sclerosis patients. Clin Neurol Neurosurg 1986; 88: 87–92

    Article  PubMed  CAS  Google Scholar 

  108. Brochet B, Michel P, Henry P. Pain complaints in outpatients with multiple sclerosis: description and consequences on disability. Pain Clinic 1992; 5: 157–64

    Google Scholar 

  109. Clifford DB, Trotter JL. Pain in multiple sclerosis. Arch Neurol 1984; 41: 1270–2

    Article  PubMed  CAS  Google Scholar 

  110. Moulin DE, Foley KM, Ebers GC. Pain syndromes in multiple sclerosis. Neurology 1988; 38: 1830–4

    Article  PubMed  CAS  Google Scholar 

  111. Svendsen KB, Jensen TS, Hansen HJ, et al. Sensory function and quality of life in patients with multiple sclerosis and pain. Pain 2005; 114(3): 473–81

    Article  PubMed  Google Scholar 

  112. Feneberg W, Meister H, Pöllmann W. Dysesthesias and pain: a multidisciplinary treatment concept [in German]. In: Wötzel C, Wehner C, Pöllmann W, et al. editors. Therapy of multiple sclerosis. 2nd ed. Munich: Pflaum, 2000: 132–8

    Google Scholar 

  113. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev 2005 Jul 20; (3): CD005454

  114. Backonja M. Anticonvulsants for the treatment of neuropathic pain syndromes. Curr Pain Headache Rep 2003 Feb; 7(1): 39–42

    Article  PubMed  Google Scholar 

  115. Finnerup NB, Gottrup H, Jensen TS. Anticonvulsants in central pain. Expert Opin Pharmacother 2002; 3: 1411–20

    Article  PubMed  CAS  Google Scholar 

  116. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003; 60(11): 1524–34

    Article  PubMed  Google Scholar 

  117. Wiffen PJ, McQuay HJ, Edwards JE, et al. Gabapentin for acute and chronic pain. Cochrane Database Syst Rev 2005 Jul 20; (3): CD005452

  118. Houtchens MK, Richert JR, Sami A, et al. Open label gabapentin treatment for pain in multiple sclerosis. Mult Scler 1997; 3: 250–3

    Article  PubMed  CAS  Google Scholar 

  119. Samkoff LM, Daras M, Tuchman AJ, et al. Amelioration of refractory dysesthetic limb pain in multiple sclerosis by gabapentin. Neurology 1997; 49: 304–5

    Article  PubMed  CAS  Google Scholar 

  120. Chandra K, Shafiq N, Pandhi P, et al. Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a randomized, double-blind clinical trial. The GONIP Trial. Int J Clin Pharmacol Ther 2006; 44(8): 358–63

    CAS  Google Scholar 

  121. Vestergaard K, Andersen G, Gottrup H, et al. Lamotrigine for central poststroke pain: a randomized controlled trial. Neurology 2001; 56: 184–90

    Article  PubMed  CAS  Google Scholar 

  122. Eisenberg E, Lurie Y, Braker C, et al. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology 2001; 57(3): 505–9

    Article  PubMed  CAS  Google Scholar 

  123. Vinik AI, Tuchman M, Safirstein B, et al. Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized, double-blind, placebo-controlled studies. Pain 2007 Mar; 128(1-2): 169–79

    Article  PubMed  CAS  Google Scholar 

  124. McCleane G. Lamotrigine can reduce neurogenic pain associated with multiple sclerosis. Clin J Pain 1998; 14: 269–70

    Article  PubMed  CAS  Google Scholar 

  125. Rosenstock J, Tuchman M, LaMoreaux L, et al. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain 2004; 110(3): 628–38

    Article  PubMed  CAS  Google Scholar 

  126. Sabatowski R, Galvez R, Cherry DA, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebocontrolled clinical trial. The 1008-045 Study Group. Pain 2004; 109(1-2): 26–35

    Article  PubMed  CAS  Google Scholar 

  127. Dworkin RH, Corbin AE, Young Jr JP, et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebocontrolled trial. Neurology 2003; 60(8): 1274–83

    Article  PubMed  CAS  Google Scholar 

  128. Siddall PJ, Cousins MJ, Otte A, et al. Pregabalin in central neuropathic pain associated with spinal cord injury: a placebocontrolled trial. Neurology 2006; 67(10): 1792–800

    Article  PubMed  CAS  Google Scholar 

  129. Vranken JH, Dijkgraaf MG, Kruis MR, et al. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen. Pain 2007 Aug 17 [Epub ahead of print]

  130. Wallin J, Cui JG, Yakhnitsa V, et al. Gabapentin and pregabalin suppress tactile allodynia and potentiate spinal cord stimulation in a model of neuropathy. Eur J Pain 2002; 6(4): 261–72

    Article  PubMed  CAS  Google Scholar 

  131. Wernicke JF, Pritchett YL, D’Souza DN, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology 2006; 67(8): 1411–20

    Article  PubMed  CAS  Google Scholar 

  132. Silver M, Blum D, Grainger J, et al. Double-blind, placebo-controlled trial of lamotrigine in combination with other medications for neuropathic pain. J Pain Symptom Manage 2007 Oct; 34(4): 446–54

    Article  PubMed  CAS  Google Scholar 

  133. Breuer B, Pappagallo M, Knotkova H, et al. A randomized, double-blind, placebo-controlled, two-period, crossover, pilot trial of lamotrigine in patients with central pain due to multiple sclerosis. Clin Ther 2007; 29(9): 2022–30

    Article  PubMed  CAS  Google Scholar 

  134. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004; 328: 991–4

    Article  PubMed  CAS  Google Scholar 

  135. Davies PS, Galer BS. Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs 2004; 64(9): 937–47

    Article  PubMed  CAS  Google Scholar 

  136. Gilron I, Watson CP, Cahill CM, et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3): 265–75

    Article  PubMed  Google Scholar 

  137. Eisenberg E, McNicol E, Carr DB. Opioids for neuropathic pain. Cochrane Database Syst Rev 2006 Jul 19; (3): CD006146

  138. Hollingshead J, Dühmke RM, Cornblath DR. Tramadol for neuropathic pain. Cochrane Database Syst Rev 2006 Jul 19; (3): CD003726

  139. Sittl R. Transdermal buprenorphine in the treatment of chronic pain. Expert Rev Neurother 2005; 5(3): 315–23

    Article  PubMed  CAS  Google Scholar 

  140. Likar R, Sittl R. Transdermal buprenorphine for treating nociceptive and neuropathic pain: four case studies. Anesth Analg 2005 Mar; 100(3): 781–785

    Article  PubMed  Google Scholar 

  141. Dellemijn PL, van Duijn H, Vanneste JA. Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Symptom Manage 1998 Oct; 16(4): 220–9

    Article  PubMed  CAS  Google Scholar 

  142. Agarwal S, Polydefkis M, Block B, et al. Transdermal fentanyl reduces pain and improves functional activity in neuropathic pain states. Pain Med 2007; 8(7): 554–62

    Article  PubMed  Google Scholar 

  143. Kaiman S, Osterberg A, Sorensen J, et al. Morphine responsiveness in a group of well-defined multiple sclerosis patients: a study with i.V. morphine. Eur J Pain 2002; 6: 69–80

    Article  CAS  Google Scholar 

  144. Attal N, Guirimand F, Brasseur L, et al. Effects of IV morphine in central pain. Neurology 2002; 58: 554–63

    Article  PubMed  CAS  Google Scholar 

  145. Raja SN, Haythornthwaite JA, Pappagallo M, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002; 59: 1015–21

    Article  PubMed  CAS  Google Scholar 

  146. Gilron I, Bailey JM, Tu D, et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005; 352(13): 1324–34

    Article  PubMed  CAS  Google Scholar 

  147. Wade DT, Robson P, House H, et al. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil 2003; 17: 21–9

    Article  PubMed  Google Scholar 

  148. Zajicek J, Fox P, Sanders H, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. UK MS Research Group. Lancet 2003; 362(9395): 1517–26

    Article  PubMed  CAS  Google Scholar 

  149. 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(7460): 253

    Article  PubMed  CAS  Google Scholar 

  150. Iskedjian M, Bereza B, Gordon A, et al. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin 2007 Jan; 23(1): 17–24

    Article  PubMed  CAS  Google Scholar 

  151. Rog DJ, Nurmikko TJ, Young CA. Oromucosal Delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther 2007; 29(9): 2068–79

    Article  PubMed  CAS  Google Scholar 

  152. Raskin P, Donofrio PD, Rosenthal NR, et al. Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects. CAPSS-141 Study Group. Neurology 2004; 63(5): 865–73

    CAS  Google Scholar 

  153. Laughlin TM, Tram KV, Wilcox GL, et al. Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception. J Pharmacol Exp Ther 2002; 302: 1168–75

    Article  PubMed  CAS  Google Scholar 

  154. Novak V, Kanard R, Kissel JT, et al. Treatment of painful sensory neuropathy with tiagabine: a pilot study. Clin Auton Res 2001; 11(6): 357–61

    Article  PubMed  CAS  Google Scholar 

  155. Mattia C, Paoletti F, Coluzzi F, et al. New antidepressants in the treatment of neuropathic pain: a review. Minerva Anestesiol 2002; 68(3): 105–14

    PubMed  CAS  Google Scholar 

  156. Sindrup SH, Bach FW, Madsen C, et al. Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial. Neurology 2003; 60: 1284–9

    Article  PubMed  CAS  Google Scholar 

  157. Schüler P, Seibel K, Chevts V, et al. Analgesic effect of the selective noradrenaline reuptake inhibitor reboxetine [in German]. Nervenarzt 2002; 73(2): 149–54

    Article  PubMed  Google Scholar 

  158. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg 2003; 97: 1730–9

    Article  PubMed  CAS  Google Scholar 

  159. Sjölund BH. Pain and rehabilitation after spinal cord injury: the case of sensory spasticity? Brain Res Brain Res Rev 2002; 40(1-3): 250–6

    Article  PubMed  Google Scholar 

  160. Eide PK, Jorum E, Stubhaug A, et al. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. Pain 1994 Sep; 58(3): 347–54

    Article  PubMed  CAS  Google Scholar 

  161. Sakai T, Tomiyasu S, Ono T, et al. Multiple sclerosis with severe pain and allodynia alleviated by oral ketamine. Clin J Pain 2004; 20(5): 375–6

    Article  PubMed  Google Scholar 

  162. Chiba S, Ito M, Matsumoto H. Amantadine treatment for refractory pain and fatigue in patients with multiple sclerosis [letter]. Can J Neurol Sci 1992; 19: 309

    PubMed  CAS  Google Scholar 

  163. Otto M, Bach FW, Jensen TS, et al. Valproic acid has no effect on pain in polyneuropathy: a randomized, controlled trial. Neurology 2004; 62: 285–8

    Article  PubMed  CAS  Google Scholar 

  164. Thienel U, Neto W, Schwabe SK, et al. Topiramate in painful diabetic polyneuropathy: findings from three double-blind placebo-controlled trials. Topiramate Diabetic Neuropathic Pain Study Group. Acta Neurol Scand 2004 Oct; 110(4): 221–31

    Article  PubMed  CAS  Google Scholar 

  165. Nix WA. What is certain in pain therapy? The analgesic potency of neuroleptics in the treatment of chronic pain: a meta analysis [in German]. Schmerz 1998; 12: 30–8

    Article  PubMed  CAS  Google Scholar 

  166. Herman RM, D’Luzansky SC, Ippolito R. Intrathecal baclofen suppresses central pain in patients with spinal lesions: a pilot study. Clin J Pain 1992; 8: 338–45

    Article  PubMed  CAS  Google Scholar 

  167. Becker R, Uhle EI, Alberti O, et al. Continuous intrathecal baclofen infusion in the management of central deafferentation pain. J Pain Symptom Manage 2000; 20: 313–5

    Article  PubMed  CAS  Google Scholar 

  168. Paice JA, Penn RD, Kroin JS. Intrathecal octreotide for relief of intractable nonmalignant pain: 5-year experience with two cases. Neurosurgery 1996; 38: 203–7

    Article  PubMed  CAS  Google Scholar 

  169. Birknes JK, Sharan A, Rezai AR. Treatment of chronic pain with neurostimulation. Prog Neurol Surg 2006; 19: 197–207

    Article  PubMed  Google Scholar 

  170. Graff-Radford SB, Shaw LR, Naliboff BN. Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia. Clin J Pain 2000; 16: 188–92

    Article  PubMed  CAS  Google Scholar 

  171. Frese A, Husstedt IW, Ringelstein EB, et al. Pharmacologic treatment of central post-stroke pain. Clin J Pain 2006; 22(3): 252–60

    Article  PubMed  CAS  Google Scholar 

  172. MedlinePlus. Drugs, supplements, and herbal information [online]. Available from URL: http://www.nlm.nih.gov/medlineplus/druginformation.html [Accessed 2008 Feb 13]

  173. Drug information [online]. Available from URL: http://www.drugs.com [Accessed 2008 Feb 13]

  174. RxList, the internet drug index [online]. Available from URL: http://www.rxlist.com [Accessed 2008 Jan 3]

  175. US Food and Drug Administration [online]. Available from URL: www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm [Accessed 2008 Jan 3]

  176. Klewer J, Pöhlau D, Nippert I, et al. Problems reported by elderly patients with multiple sclerosis. J Neurosci Nurs 2001; 33: 167–71

    Article  PubMed  CAS  Google Scholar 

  177. Wötzel C, Wehner C, Pöllmann W, et al., editors. Therapy of multiple sclerosis [in German].2nded.Munich: Pflaum, 2000: 1–230

    Google Scholar 

  178. Haselkorn JK, Balsdon Richer C, Fry Welch D, et al. Multiple Sclerosis Council for Clinical Practice guidelines. Overview of spasticity management in multiple sclerosis: evidence-based management strategies for spasticity treatment in multiple sclerosis. J Spinal Cord Med 2005; 28(2): 167–99

    PubMed  CAS  Google Scholar 

  179. Khan F, Turner-Stokes L, Ng L, et al. Multidisciplinary rehabilitation for adults with multiple sclerosis. Cochrane Database Syst Rev 2007 Apr 18; (2): CD 006036.

  180. Rietberg MB, Brooks D, Uitdehaag BM, et al. Exercise therapy for multiple sclerosis. Cochrane Database Syst Rev 2005 Jan 25; (1): CD003980

  181. Rietberg MB, Brooks D, Uitdehaag BMJ, et al. Exercise therapy for multiple sclerosis. Cochrane Database of Systematic Reviews 2004; (3): CD003980

  182. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987 Feb; 67(2): 206–7.

    PubMed  CAS  Google Scholar 

  183. Allison SC, Abraham LD. Sensitivity of qualitative and quantitative spasticity measures to clinical treatment with cryotherapy. Int J Rehabil Res 2001 Mar; 24(1): 15–24

    Article  PubMed  CAS  Google Scholar 

  184. Miller L, Mattison P, Paul L, et al. The effects of transcutaneous electrical nerve stimulation (TENS) on spasticity in multiple sclerosis. Mult Scler 2007 May; 13(4): 527–33

    PubMed  CAS  Google Scholar 

  185. Rizzo MA, Hadjimichael OC, Preiningerova J, et al. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler 2004 Oct; 10(5): 589–95

    Article  PubMed  CAS  Google Scholar 

  186. Sachais BA, Logue JN, Carey MS. Baclofen, a new antispastic drug: a controlled, multicenter trial in patients with multiple sclerosis. Arch Neurol 1977; 34: 422–8

    Article  PubMed  CAS  Google Scholar 

  187. Ward AB, Kadies M. The management of pain in spasticity. Disabil Rehabil 2002; 24: 443–53

    Article  PubMed  CAS  Google Scholar 

  188. Shakespeare D, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev 2003; (4): CD001332

  189. Mueller ME, Gruenthal M, Olson WL, et al. Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis. Arch Phys Med Rehabil 1997; 78: 521–4

    Article  PubMed  CAS  Google Scholar 

  190. Solaro C, Uccelli MM, Guglieri P, et al. Gabapentin is effective in treating nocturnal painful spasms in multiple sclerosis. Mult Scler 2000; 6: 192–3

    PubMed  CAS  Google Scholar 

  191. Cutter NC, Scott DD, Johnson JC, et al. Gabapentin effect on spasticity in multiple sclerosis: a placebo-controlled, randomised trial. Arch Phys Med Rehabil 2000; 81: 164–9

    PubMed  CAS  Google Scholar 

  192. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculo-skeletal conditions: a systematic review. J Pain Symptom Manage 2004; 28(2): 140–75

    Article  PubMed  CAS  Google Scholar 

  193. Schapiro RT. Management of spasticity, pain, and paroysmal phenomena in multiple sclerosis. Curr Neurol Neurosci Reports 2001; 1: 299–302

    Article  CAS  Google Scholar 

  194. Hawker K, Frohman E, Racke M. Levetiracetam for phasic spasticity in multiple sclerosis. Arch Neurol 2003; 60: 1772–4

    Article  PubMed  Google Scholar 

  195. Vaney C, Heinzel-Gutenbrunner M, Jobin P, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult Scler 2004; 10: 417–24

    Article  PubMed  CAS  Google Scholar 

  196. Wade DT, Makela P, Robson P, et al. 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 2004; 10: 434–41

    Article  PubMed  CAS  Google Scholar 

  197. Wissel J, Haydn T, Muller J, et al. Low dose treatment with the synthetic cannabinoid nabilone significantly reduces spasticity-related pain: a double-blind placebo-controlled cross-over trial. J Neurol 2006 Oct; 253(10): 1337–41

    Article  PubMed  CAS  Google Scholar 

  198. Wade DT, Makela PM, House H, et al. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult Scler 2006; 12(5): 639–45

    Article  PubMed  CAS  Google Scholar 

  199. Lang AM. Botulinum toxin type A therapy in chronic pain disorders. Arch Phys Med Rehabil 2003; 84(3 Suppl. 1): S69–73

    Article  PubMed  Google Scholar 

  200. Göbel H, Jost WH. Botulinum toxin in specific pain therapy. Schmerz 2003; 17: 149–65

    Article  PubMed  Google Scholar 

  201. Wissel J, Muller J, Dressnandt J, et al. Management of spasticity associated pain with botulinum toxin A. J Pain Symptom Manage 2000; 20: 44–9

    Article  PubMed  CAS  Google Scholar 

  202. Mancini F, Sandrini G, Moglia A, et al. A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot. Neurol Sci 2005; 26(1): 26–31

    Article  PubMed  CAS  Google Scholar 

  203. Chalkiadaki A, Rohr UP, Hefter H. Early pain reduction in the treatment of spasticity after a single injection of botulinum A toxin [in German]. Dtsch Med Wochenschr 2001; 126: 1361–4

    Article  PubMed  CAS  Google Scholar 

  204. Cardoso E, Rodrigues B, Lucena R, et al. Botulinum toxin type A for the treatment of the upper limb spasticity after stroke: a meta-analysis. Arq Neuropsiquiatr 2005; 63(1): 30–3

    Article  PubMed  Google Scholar 

  205. Hyman N, Barnes M, Bhakta B, et al. Botulinum toxin (Dysport) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study. J Neurol Neurosurg Psychiatry 2000; 68(6): 707–12

    Article  PubMed  CAS  Google Scholar 

  206. Dario A, Scamoni C, Bono G, et al. Functional improvement in patients with severe spinal spasticity treated with chronic intrathecal baclofen infusion. Funct Neurol 2001; 16: 311–5

    PubMed  CAS  Google Scholar 

  207. Middel B, Kuipers-Upmeijer H, Bouma J, et al. Effect of intrathecal baclofen delivered by an implanted programmable pump on health-related quality of life in patients with severe spasticity. J Neurol Neurosurg Psychiatry 1997; 63: 204–9

    Article  PubMed  CAS  Google Scholar 

  208. Ochs A, Tonn JC. Functional outcome and clinical significance of long-term intrathecal baclofen therapy for severe spasticity. J Neuro Rehab 1996; 10: 159–66

    Google Scholar 

  209. Dahm PO, Nitescu PV, Appelgren LK, et al. Long-term intrathecal (i.t.) infusion of bupivacaine relieved intractable pain and spasticity in a patient with multiple sclerosis. Eur J Pain 1998; 2: 81–5

    Article  PubMed  Google Scholar 

  210. Jarrett L, Nandi P, Thompson AJ. Managing severe lower limb spasticity in multiple sclerosis: does intrathecal phenol have a role? J Neurol Neurosurg Psychiatry 2002; 73: 705–9

    Article  PubMed  CAS  Google Scholar 

  211. Heun R, Emser W, Schimrigk K. Evoked potentials under intrathecal and systemic corticosteroid application in patients with multiple sclerosis [in German]. Z EEG-EMG 1987; 20: 88–91

    Google Scholar 

  212. Hoffmann V, Schimrigk S, Islamova S, et al. Efficacy and safety of repeated intrathecal triamcinolone acetonide application in progressive multiple sclerosis patients. J Neurol Sci 2003; 211: 81–4

    Article  PubMed  CAS  Google Scholar 

  213. Salame K, Ouaknine GE, Rochkind S, et al. Surgical treatment of spasticity by selective posterior rhizotomy: 30 years experience. Isr Med Assoc J 2003; 5(8): 543–6

    PubMed  Google Scholar 

  214. Penn RD. Intrathecal baclofen for spasticity of spinal origin: seven years of experience. J Neurosurg 1992 Aug; 77(2): 236–40.

    Article  PubMed  CAS  Google Scholar 

  215. Gibson J, Frank A. Pain experienced by electric-powered chair users: a pilot exploration using pain drawings. Physiother Res Int 2005; 10(2): 110–5

    Article  PubMed  Google Scholar 

  216. Philadelphia Panel. Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions for neck pain. Phys Ther 2001; 81: 1701–17

    Google Scholar 

  217. Philadelphia Panel. Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions for shoulder pain. Phys Ther 2001; 81: 1719–30

    Google Scholar 

  218. Philadelphia Panel. Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions for knee pain. Phys Ther 2001; 81: 1675–700

    Google Scholar 

  219. Feine JS, Lund JP. An assessment of the efficacy of physical therapy and physical modalities for the control of chronic musculoskeletal pain. Pain 1997; 71: 5–23

    Article  PubMed  CAS  Google Scholar 

  220. Korthals-de Bos IB, Hoving JL, van Tulder MW, et al. Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial. BMJ 2003; 326: 911

    PubMed  Google Scholar 

  221. Price CI. Shoulder pain after stroke: a research challenge. Age Ageing 2002; 31Suppl. 3: 36–8

    Article  PubMed  Google Scholar 

  222. Turner-Stokes L, Jackson D. Shoulder pain after stroke: a review of the evidence base to inform the development of an integrated care pathway. Clin Rehabil 2002; 16: 276–98

    Article  PubMed  Google Scholar 

  223. Lim JY, Koh JH, Paik NJ. Intramuscular botulinum toxin-A reduces hemiplegic shoulder pain: a randomized, double-blind, comparative study versus intraarticular triamcinolone acetonide. Stroke 2008 Jan; 39(1): 126–31

    Article  PubMed  CAS  Google Scholar 

  224. Kidd BL, Langford RM, Wodehouse T. Arthritis and pain: current approaches in the treatment of arthritic pain. Arthritis Res Ther 2007; 9(3): 214

    Article  PubMed  CAS  Google Scholar 

  225. Schnitzer TJ. Update on guidelines for the treatment of chronic musculoskeletal pain. Clin Rheumatol 2006; 25Suppl. 1: 22–9

    Article  Google Scholar 

  226. Towheed TE, Maxwell L, Judd MG, et al. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006; (1): CD004257

  227. Jalan R, Williams R, Bernuau J. Paracetamol: are therapeutic doses entirely safe? Lancet 2006 Dec 23; 368(9554): 2195–6

    Article  PubMed  Google Scholar 

  228. Porcheret M, Jordan K, Croft P. Treatment of knee pain in older adults in primary care: development of an evidence-based model of care. Primary Care Rhumatology Society. Rheumatology (Oxford) 2007; 46(4): 638–48

    Article  CAS  Google Scholar 

  229. Qerama E, Fuglsang-Frederiksen A, Kasch H, et al. A double-blind, controlled study of botulinum toxin A in chronic my-ofascial pain. Neurology 2006 Jul 25; 67(2): 241–5

    Article  PubMed  CAS  Google Scholar 

  230. Albrecht H, Pöllmann W, König N. Acute foot drop paralysis in multiple sclerosis: peroneal nerve compression as differential diagnosis of acute onset [in German]. Nervenarzt 1996; 67: 163–9

    PubMed  CAS  Google Scholar 

  231. Henze T, Rieckmann P, Toyka KV. Symptomatic treatment of multiple sclerosis. Multiple Sclerosis Therapy Consensus Group (MSTCG) of the German Multiple Sclerosis Society. Eur Neurol 2006; 56(2): 85–7

    Article  Google Scholar 

  232. Henze T, Rieckmann P, Toyka KV. Symptomatic treatment of multiple sclerosis. Multiple Sclerosis Therapy Consensus Group (MSTCG) of the German Multiple Sclerosis Society. Eur Neurol 2006; 56(2): 87–8

    Article  Google Scholar 

  233. Brochet B, Lemaire G, Beddiaf A. Reduction of injection site reactions in multiple sclerosis (MS) patients newly started on interferon beta 1b therapy with two different devices [in French]. l’Epicure Study Group. Rev Neurol (Paris) 2006; 162(6-7): 735–40

    Article  PubMed  CAS  Google Scholar 

  234. Buhse M. Efficacy of EMLA cream to reduce fear and pain associated with interferon beta-1a injection in patients with multiple sclerosis. J Neurosci Nurs 2006; 38(4): 222–6

    Article  PubMed  Google Scholar 

  235. Neilley LK, Goodin DS, Goodkin DE, et al. Side effect profile of interferon beta-1b in MS: results of an open label trial. Neurology 1996; 46: 552–4

    Article  PubMed  CAS  Google Scholar 

  236. Reess J, Haas J, Gabriel K, et al. Both paracetamol and ibuprofen are equally effective in managing flu-like symptoms in relapsing-remitting multiple sclerosis patients during interferon beta-1a (AVONEX) therapy. Mult Scler 2002; 8: 15–8

    PubMed  CAS  Google Scholar 

  237. Walther EU, Hohlfeld R. Multiple sclerosis: side effects of interferon beta therapy and their management. Neurology 1999 Nov 10; 53(8): 1622–7

    Article  PubMed  CAS  Google Scholar 

  238. Rio J, Nos C, Bonaventura I, et al. Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-1a flu symptoms in MS: a randomized trial. Neurology 2004; 63(3): 525–8

    Article  PubMed  CAS  Google Scholar 

  239. Leuschen MP, Filipi M, Healey K. A randomized open label study of pain medications (naproxen, acetaminophen and ibuprofen) for controlling side effects during initiation of IFN beta-1a therapy and during its ongoing use for relapsing-remitting multiple sclerosis. Mult Scler 2004 Dec; 10(6): 636–42

    Article  PubMed  CAS  Google Scholar 

  240. Pöllmann W, Erasmus L-P, Feneberg W, et al. Interferon beta but not glatiramer acetate therapy aggravates headaches in MS. Neurology 2002; 59: 636–9

    Article  PubMed  Google Scholar 

  241. Evers S, Afra J, Frese A, et al. EFNS guideline on the drug treatment of migraine: report of an EFNS task force. Eur J Neurol 2006; 13(6): 560–72

    Article  PubMed  CAS  Google Scholar 

  242. Soos N, Shakery K, Mrowietz U. Localized panniculitis and subsequent lipoatrophy with subcutaneous glatiramer acetate (Copaxone) injection for the treatment of multiple sclerosis. Am J Clin Dermatol 2004; 5(5): 357–9

    Article  PubMed  Google Scholar 

  243. Pöllmann W, Erasmus LP, Feneberg W, et al. The effect of glatiramer acetate treatment on pre-existing headaches in patients with MS. Neurology 2006; 66(2): 275–7

    Article  PubMed  CAS  Google Scholar 

  244. Katz U, Kishner I, Magalashvili D, et al. Long-term safety of IVIg therapy in multiple sclerosis: 10 years experience. Autoimmunity 2006 Sep; 39(6): 513–7

    Article  PubMed  Google Scholar 

  245. Finkel AG, Howard JF, Mann JD. Successful treatment of headache related to intravenous immunglobulin with antimigraine medication. Headache 1998; 38: 317–21

    Article  PubMed  CAS  Google Scholar 

  246. Koes BW, van Tulder MW, Thomas S. Diagnosis and treatment of low back pain. BMJ 2006; 332(7555): 1430–4

    Article  PubMed  CAS  Google Scholar 

  247. van Tulder M, Becker A, Bekkering T, et al. European guidelines for the management of acute nonspecific low back pain in primary care (chapter 3). The COST B13 Working Group on Guidelines for the Management of Acute Low Back Pain in Primary Care. Eur Spine J 2006 Mar; 15Suppl. 2: S169–91

    Article  PubMed  Google Scholar 

  248. Philadelphia Panel. Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions for low back pain. Phys Ther 2001; 81: 1641–74

    Google Scholar 

  249. Hayden JA, van Tulder MW, Malmivaara A, et al. Exercise therapy for treatment of non-specific low back pain. Cochrane Database Syst Rev 2005 Jul 20; (3): CD000335

  250. Khadilkar A, Milne S, Brosseau L, et al. Transcutaneous electrical nerve stimulation for the treatment of chronic low back pain: a systematic review. Spine 2005; 30(23): 2657–66

    Article  PubMed  Google Scholar 

  251. Al-Smadi J, Warke K, Wilson I, et al. A pilot investigation of the hypoalgesic effects of transcutaneous electrical nerve stimulation upon low back pain in people with multiple sclerosis. Clin Rehabil 2003; 17: 742–9

    Article  PubMed  CAS  Google Scholar 

  252. Warke K, Al-Smadi J, Baxter D, et al. Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: a randomized, placebo-controlled clinical trial. Clin J Pain 2006; 22(9): 812–9

    Article  PubMed  Google Scholar 

  253. Airaksinen O, Brox JI, Cedraschi C, et al. European guidelines for the management of chronic nonspecific low back pain. The COST B13 Working Group on Guidelines for Chronic Low Back Pain. Eur Spine J 2006 Mar; 15Suppl. 2: S192–300

    Article  PubMed  Google Scholar 

  254. Kalso E, Allan L, Dobrogowski J, et al. Do strong opioids have a role in the early management of back pain? Recommendations from a European expert panel. Curr Med Res Opin 2005; 21(11): 1819–28

    Article  PubMed  Google Scholar 

  255. Foster L, Clapp L, Erickson M, et al. Botulinum toxin A and chronic low back pain: a randomised, double-blind study. Neurology 2001; 56: 1290–3

    Article  PubMed  CAS  Google Scholar 

  256. Leibing E, Leonhardt U, Koster G, et al. Acupuncture treatment of chronic low-back pain: a randomized, blinded, placebo-controlled trial with 9-month follow-up. Pain 2002; 96: 189–96

    Article  PubMed  Google Scholar 

  257. Ramirez-Lassepas M, Tulloch JW, et al. Acute radicular pain as a presenting symptom in multiple sclerosis. Arch Neurol 1992; 49: 255–8

    Article  PubMed  CAS  Google Scholar 

  258. Portenoy RK, Yang K, Thorton D. Chronic intractable pain: an atypical presentation of multiple sclerosis. J Neurol 1988; 235: 226–8

    Article  PubMed  CAS  Google Scholar 

  259. Armingeat T, Brondino R, Pham T, et al. Intravenous pamidronate for pain relief in recent osteoporotic vertebral compression fracture: a randomized double-blind controlled study. Osteoporos Int 2006; 17(11): 1659–65

    Article  PubMed  CAS  Google Scholar 

  260. Goemaere S, Van Laere M, De Neve P, et al. Bone mineral status in paraplegic patients who do or do not perform standing. Osteoporos Int 1994; 4: 138–43

    Article  PubMed  CAS  Google Scholar 

  261. La Mantia L, D’Amico D, Rigamonti A, et al. Interferon treatment may trigger primary headaches in multiple sclerosis patients. Mult Scler 2006; 12(4): 476–80

    Article  PubMed  Google Scholar 

  262. Rasmussen BK. Epidemiology of headache. Cephalalgia 1995; 15: 45–68

    PubMed  CAS  Google Scholar 

  263. Lampl C, Buzath A, Baumhackl U, et al. One-year prevalence of migraine in Austria: a nation-wide survey. Cephalalgia 2003; 23: 280–6

    Article  PubMed  CAS  Google Scholar 

  264. Freedman MS, Gray TA. Vascular headache: a presenting symptom of multiple sclerosis. Can J Neurol Sci 1989; 16: 63–6

    PubMed  CAS  Google Scholar 

  265. Weiller C, May A, Limmroth V, et al. Brain stem activation in spontaneous human migraine attacks. Nature Med 1995; 1(7): 658–60

    Article  PubMed  CAS  Google Scholar 

  266. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society [summary for patients in Ann Intern Med 2007 Oct 2; 147(7): 145]. Clinical Efficacy Assessment Subcommittee of the American College of Physicians, American College of Physicians, American Pain Society Low Back Pain Guidelines Panel. Ann Intern Med 2007 Oct 2; 147(7): 478–91

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Mrs J. Benson for copyediting the manuscript.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Walter Pöllmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pöllmann, W., Feneberg, W. Current Management of Pain Associated with Multiple Sclerosis. CNS Drugs 22, 291–324 (2008). https://doi.org/10.2165/00023210-200822040-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200822040-00003

Keywords

Navigation