Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Neurology and Neuroscience Reports
Published in: Current Neurology and Neuroscience Reports 1/2013

01-01-2013 | Demyelinating Disorders (DN Bourdette and V Yadav, Section Editors)

Pain and Multiple Sclerosis: Pathophysiology and Treatment

Authors: Claudio Solaro, Erika Trabucco, Michele Messmer Uccelli

Published in: Current Neurology and Neuroscience Reports | Issue 1/2013

Login to get access

Abstract

Pain is a common symptom in multiple sclerosis (MS) and has recently been estimated to be experienced by up to 75 % of patients. Pain can be present at any point in the course of the disease and patients may experience pain from various causes simultaneously. Pain in MS can also be secondary to other symptoms, such as spasticity, fatigue, and mood disorder. Of all drug use to treat MS symptoms, treatment for pain accounts for nearly 30 % of total use. At the same time, patients report low satisfaction with pain management. Pain affects quality of life and can influence a person’s participation in family life and work and affect mood. Most of the pain literature in the field of MS is based on open-label studies involving small numbers of subjects. Placebo-controlled trials in severe pain syndromes such as trigeminal neuralgia are unethical but for other types of MS-related pain conditions, placebo-controlled trials are ethical and necessary to establish efficacy, particularly given the well-documented placebo effect for various painful conditions This review discusses available data and emphasizes areas of pain research that require further attention
Literature
1.
Paty DW, Ebers GC. Multiple sclerosis 135–191. Philadelphia: F.A. Davis Company; 1999. p. 135–91.
2.
Brichetto G, Messmer Uccelli M, Mancardi GL, Solaro C. Symptomatic medication use in multiple sclerosis. Mult Scler. 2003;9(5):458–60.PubMedCrossRef
3.
"Part III: pain terms, a current list with definitions and notes on usage" (pp 209–214) Classification of chronic pain, second edition, IASP Task Force on Taxonomy, edited by H. Merskey and N. Bogduk, IASP Press, Seattle; 1994. p. 209–14.
4.
Treede RD, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–5.PubMedCrossRef
5.
O’Connor AB, Schwid SR, Herrmann DN, Markman JD, Dworkin RH. Pain associated with multiple sclerosis: systematic review and proposed classification. Pain. 2008;137:96–111.PubMedCrossRef
6.
7.
Vermote R, Ketalaer P, Carltonn H. Pain in multiple sclerosis patients: a prospective study using the McGill pain questionnaire. Clin Neurol Neurosurg. 1986;88:87–93.PubMedCrossRef
8.
Kassirer MR, Osterberg DH. Pain in chronic multiple sclerosis. J Pain Symptom Manage. 1987;2:95–7.PubMedCrossRef
9.
10.
Stenager E, Knutsen L, Jensen K. Acute and chronic pain syndromes in multiple sclerosis. Acta Neurol Scand. 1991;84:197–200.PubMedCrossRef
11.
Warnell P. The pain experience of a multiple sclerosis population: a descriptive study. Axon. 1991;13:26–8.PubMed
12.
Archibald CJ, et al. Pain prevalence, severity and impact in a clinical sample of multiple sclerosis patients. Pain. 1994;58:89–93.PubMedCrossRef
13.
Indaco A, Iachetta C, Nappi C, Socci L, Carrieri PB. Chronic and acute pain syndromes in patients with multiple sclerosis. Acta Neurol. 1994;16:97–102.
14.
Stenager E, Knudsen L, Jensen K. Acute and chronic pain syndromes in multiple sclerosis. Ital J Neurol Sci. 1995;16:629–32.PubMedCrossRef
15.
Beiske AG, Pedersen ED, Czujko B, Myhr KM. Pain and sensory complaints in multiple sclerosis. Eur J Neurol. 2004;1:479–82.CrossRef
16.
Ehde DM, et al. Chronic pain in a large community sample of persons with multiple sclerosis. Mult Scler. 2003;6:605–11.CrossRef
17.
Svendsen KB, et al. Pain in patients with multiple sclerosis: a population-based study. Arch Neurol. 2003;60:1089–94.PubMedCrossRef
18.
Solaro C, et al. The prevalence of pain in multiple sclerosis. A multicenter cross-sectional study. Neurology. 2004;63:919–21.PubMedCrossRef
19.
Österberg A, Boivie J, Thomas KA. Central pain in multiple sclerosis-prevalence and clinical characteristics. Eur J Pain. 2005;9:531–42.PubMedCrossRef
20.
Ehde DM, Osborne TL, Hanley MA, Jensen MP, Kraft GH. The scope and nature of pain in persons with multiple sclerosis. Mult Scler. 2006;12:629–38.PubMedCrossRef
21.
Hadjimichael O, Kerns RD, Rizzo MA, Cutter G, Vollmer T. Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain. 2007;127:35–41.PubMedCrossRef
22.
Piwko C, et al. Pain due to multiple sclerosis: analysis of the prevalence and economic burden in Canada. Pain Res Manag. 2007;12:259–65.PubMed
23.
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;8:614–23.PubMed
24.
Boneschi M, et al. Lifetime and actual prevalence of pain and headache in multiple sclerosis. Mult Scler. 2008;14:514–21.CrossRef
25.
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. 2008;89:1923–32.PubMedCrossRef
26.
Hirsh AT, Turner AP, Ehde DM, Haselkorn JK. Prevalence and impact of pain in multiple sclerosis: physical and psychological contributors. Arch Phys Med Rehabil. 2009;90:646–51.PubMedCrossRef
27.
Seixa D, Vasco Galhardo MJ, Guimarães J, Lima L. Pain in Portuguese patients with multiple sclerosis. Front Neurol. 2011;2:20.
28.
Aicher SA, Silverman MB, Winkler CW, Bebo Jr BF. Hyperalgesia in an animal model of multiple sclerosis. Pain. 2004;110:560–70.PubMedCrossRef
29.
• Olechowski CJ, Truong JJ, Kerr BJ. Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encephalomyelitis (EAE). Pain. 2009;141(1–2):156–64. This article reports the dysregulation of glutamate transport function in abnormal pain behavior in response to persistent noxious stimulation in EAE mice.PubMedCrossRef
30.
• Thibault K, Calvino B, Pezet S. Characterisation of sensory abnormalities observed in an animal model of multiple sclerosis: a behavioural and pharmacological study. Eur J Pain. 2011;15(3):231.e1–231.e16. This article reports the clinical signs linked to pain in two models of EAE related to time-course changes in disease representing a model of sensory abnormalities in MS. Thibault et al. also reported pain relief with medications such as gabapentin, duloxetine, and tramadol.CrossRef
31.
32.
Waxman SG, Dib-Hajj S, Cummins TR, Black JA. Sodium channels and pain. Proc Natl Acad Sci USA. 1999;96(14):7635–9. 6.PubMedCrossRef
33.
• Svendsen KB, Sørensen L, Jensen TS, Hansen HJ, Bach FW. MRI of the central nervous system in MS patients with and without pain. Eur J Pain. 2011;15(4):395–401. This study compares 13 subjects with MS with chronic pain and ten patients without pain. There was no association between chronic pain and the site of demyelinating lesions.PubMedCrossRef
34.
35.
Solaro C, Brichetto G, Battaglia MA, Messmer Uccelli M, Mancardi GL. Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study. Neurol Sci. 2005;25:307–10.PubMedCrossRef
36.
Killian JM, Fromm GH. Carbamazepine in the treatment of neuralgia: use and side effects. Arch Neurol. 2001;19:129–36.CrossRef
37.
Shirzadi M, Alvestad S, Hovdal H, et al. Comparison of carbamazepine rash in multiple sclerosis and epilepsy. Acta Neurol Scand. 2012;125(1):60–3.PubMedCrossRef
38.
Cianchetti C, Zuddas A, Randazzo AP, Perra L, Marrosu MG. Lamotrigine adjunctive therapy in painful phenomena in MS: preliminary observations. Neurology. 1999;53:433.PubMedCrossRef
39.
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. 2007;29:2022–30.PubMedCrossRef
40.
Houtchens MK, Richert JR, Sami A, Rose JW. Open label gabapentin treatment for pain in multiple sclerosis. Mult Scler. 1997;3:250–3.PubMedCrossRef
41.
Rossi S, et al. Effects of Levetiracetam on chronic pain in multiple sclerosis: results of a randomized placebo-controlled study. Eur J Neurol. 2009;16:360–6.PubMedCrossRef
42.
• Falah M, Madsen C, Holbech JV, Sindrup SH. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis. Eur J Pain. 2011;1532–2149. This study is a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3,000 mg/day versus placebo. There were no differences in the ratings of pain relief but an effect in patients with lancinating pain or without touch-evoked pain was observed.
43.
Solaro C, Boemker M, Tanganelli P. Pregabalin for treating paroxysmal symptoms in multiple sclerosis: a pilot study. J Neurol. 2009;256:1773–4.PubMedCrossRef
44.
Solaro C, Tanganelli P. Acute delirium in patients with multiple sclerosis treated with pregabalin. Clin Neuropharmacol. 2009;32:236–7.PubMedCrossRef
45.
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.PubMedCrossRef
46.
Sadiq S, Poopatana C. Intrathecal basclofen and morphine in multiple sclerosis patients with severe pain and spasticity. J Neurol. 2007;254:1464–5.PubMedCrossRef
47.
Kalman S, Österbergn A, Sörensenn 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. 2002;6:69–80.PubMedCrossRef
48.
Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 2004;329:253.PubMedCrossRef
49.
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;29:2068–79.PubMedCrossRef
50.
Zajicek J, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003;362:1517–26.PubMedCrossRef
51.
Wade DT, 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. 2004;10:434–41.PubMedCrossRef
52.
53.
54.
• Mills RJ, Young CA, Smith ET. Central trigeminal involvement in multiple sclerosis using high-resolution MRI at 3T. Br J Radiol. 2010;83:493–8. The objective of this study was to determine the prevalence of trigeminal lesions using high-resolution MRI at 3T. Forty-seven patients with MS with a high prevalence of detectable trigeminal abnormalities were studied. MRI results did not correspond to trigeminal symptoms.PubMedCrossRef
55.
•• Cruccu G, et al. Trigeminal neuralgia and pain related to multiple sclerosis. Pain. 2009;143:186–91. MRI scans were performed on 130 patients with MS: 50 with trigeminal neuralgia, 30 with trigeminal sensory disturbances other than trigeminal neuralgia and 50 without pain. Cruccu et al. concluded that the most likely cause of MS-related trigeminal neuralgia is a pontine plaque damaging the primary afferents. Nevertheless, in some patients a neurovascular contact may act as a concurring mechanism.PubMedCrossRef
56.
Hutchins LG, Harnsberger HR, Jacobs JM, Apfelbaum RI. Trigeminal neuralgia (tic douloureux): MR imaging assessment. Radiology. 1990;175:837–41.PubMed
57.
Lazar ML, Kirkpatrick JB. Trigeminal neuralgia and multiple sclerosis: demonstration of the plaque in an operative case. Neurosurgery. 1979;5:711–7.PubMedCrossRef
58.
Da Silva CJ, Da Rocha AJ, Mendes MF, Maja Jr ACM, Braga FT, Tilbery CP. Trigeminal involvement in multiple sclerosis: magnetic resonance imaging findings with clinical correlation in a series of patients. Mult Scler. 2005;11:282–5.PubMedCrossRef
59.
Nakashima I, Fujihara K, Kimpara T, Okita N, Takase S, Itoyama Y. Linear pontine trigeminal root lesions in multiple sclerosis: clinical and magnetic resonance imaging studies in 5 cases. Arch Neurol. 2001;58:101–4.PubMedCrossRef
60.
Gass A, Kitchen N, MacManus DG, Moseley IF, Hennerici MG, Miller DH. Trigeminal neuralgia in patients with multiple sclerosis: lesion localization with magnetic resonance imaging. Neurology. 1997;49(4):1142–4.PubMedCrossRef
61.
Meaney JFM, Watt JMG, Eldridge PR, Whitehouse GH, Wells JCD, Miles JB. Association between trigeminal neuralgia and multiple sclerosis: role of magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 1995;59:253–9.PubMedCrossRef
62.
Broggi G, Ferroli P, Franzini A, Nazzi V, Farina L, La Mantia L, Milanese C. 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.PubMedCrossRef
63.
Cruccu G, Leandri M, Feliciani M, Manfredi M. Idiopathic and symptomatic trigeminal pain. J Neurol Neurosurg Psychiatry. 1990;53(12):1034–42.PubMedCrossRef
64.
Bergamaschi R, Romani A, Versino M, Callieco R, Gaspari D, Citterio A, Cosi V. Usefulness of trigeminal somatosensory evoked potentials to detect subclinical trigeminal impairment in multiple sclerosis patients. Acta Neurol Scand. 1994;89:412–4.PubMedCrossRef
65.
Ramsaransing G, Zwanikken C, De Keyser J. Worsening of symptoms of multiple sclerosis associated with carbamazepine. BMJ. 2000;320:1113.PubMedCrossRef
66.
Leandri M, et al. Lamotrigine in trigeminal neuralgia secondary to multiple sclerosis. J Neurol. 2000;247:556–8.PubMedCrossRef
67.
Solaro C, et al. An open-label trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients. Neurology. 1998;51:609–11.PubMedCrossRef
68.
Solaro C, Uccelli MM, Brichetto G, Gasperini C, Mancardi GL. Topiramate relieves idiopathic and symptomatic trigeminal neuralgia. J Pain Symptom Manage. 2001;21:367–8.PubMedCrossRef
69.
Solaro C, Uccelli MM, Uccelli A, Leandri M, Mancardi GL. 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.PubMedCrossRef
70.
DMKG Study Group. Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis. J Neurol. 2003;250(542–545).
71.
Lunardi G, et al. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology. 1997;48:1714–7.PubMedCrossRef
72.
Khan OA. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients. Neurology. 1998;51:611–4.PubMedCrossRef
73.
Zvartau-Hind M, Din MU, Gilan A, Lisak RP, Khan OA. Topiramate relieves refractory trigeminal neuralgia in MS patients. Neurology. 2000;55:1587–8.PubMedCrossRef
74.
Reder AT, Arnason B. Trigeminal neuralgia in multiple sclerosis relieved by a prostaglandin E analogue. Neurology. 1995;45:1097–100.PubMedCrossRef
75.
Linderoth B, Hakanson S. Paroxysmal facial pain in disseminated sclerosis treated by retrogasserian glycerol injection. Acta Neurol Scand. 1989;80:341–6.PubMedCrossRef
76.
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
77.
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
78.
Broggi G, Franzini A. Radiofrequency trigeminal rhizotomy in treatment of symptomatic non-neoplastic facial pain. J Neurosurg. 1982;57:483–6.PubMedCrossRef
79.
Rogers CL, et al. Gamma knife radiosurgery for trigeminal neuralgia associated with multiple sclerosis. J Neurosurg. 2002;97 Suppl 5:529–32.PubMed
80.
Huang E, et al. Gamma knife radiosurgery for treatment of trigeminal neuralgia in multiple sclerosis patients. Stereotact Funct Neurosurg. 2002;79:44–50.PubMedCrossRef
81.
Broggi G, et al. Role of microvascular decompression in trigeminal neuralgia and multiple sclerosis. Lancet. 1999;354:1878–9.PubMedCrossRef
82.
Al-Araji AH, Oger J. Reappraisal of Lhermitte’s sign in multiple sclerosis. Mult Scler. 2005;11:398–402.PubMedCrossRef
83.
84.
Solaro C, Uccelli MM, Guglieri P, Uccelli A, Mancardi GL. Gabapentin is effective in treating nocturnal painful spasms in multiple sclerosis. Mult Scler. 2000;6:192–3.PubMed
85.
Solaro C, Tanganelli P. Tiagabine for treating painful tonic spasms in multiple sclerosis: a pilot study. J Neurol Neurosurg Psychiatry. 2004;75:341.PubMed
86.
Restivo DA, Tinazzi M, Patti F, Palmeri A, Maimone D. Botulinum toxin treatment of painful tonic spasms in multiple sclerosis. Neurology. 2003;61:719–20.PubMedCrossRef
87.
88.
Solaro C, Messmer Uccelli M. Management of pain in multiple sclerosis: a pharmacological approach. Nat Rev Neurol. 2011;7:519–27.PubMedCrossRef
89.
Lienau FS, Füllgraf H, Moser A, Feuerstein TJ. Why do cannabinoids not show consistent effects as analgesic drugs in multiple sclerosis? Eur J Neurol. 2007;14:1162–9.PubMedCrossRef
90.
Marrie RA, Horwitz RI, Cutter G, Tyry T, Vollmer T. Association between comorbidity and clinical characteristics of MS. Acta Neurol Scand. 2010;29:135–41.
91.
Haythornthwaite JA, Benrud-Larsen LM. Psychological aspects of neuropathic pain. Clin J Pain. 2000;16:S101–5.PubMedCrossRef
92.
Duarte R. In: Kanner R, editor. Pain management secrets, vol. 6. Philadelphia: Hanley & Belfus; 2003.
93.
• Saverino A, Solaro C. Pain in individuals with multiple sclerosis, knee prosthesis, and post-herpetic neuralgia: learning from focus group patients' experience. Clin J Pain. 2012;28(4):300–8. Unique, spontaneous descriptors, possibly disease-specific, emerged in various focus groups of subjects with MS and other diseases. All disease groups used descriptors not included in the McGill Pain Questionnaire, underlining the need for assessment measures of pain based on individual perception.PubMedCrossRef
94.
Vermote R, Ketalaer P, Carlton H. Pain in multiple sclerosis patients: a prospective study using the McGill Pain Questionnaire. Clin Neurol Neurosurg. 1986;88:87–93.PubMedCrossRef
Metadata
Title
Pain and Multiple Sclerosis: Pathophysiology and Treatment
Authors
Claudio Solaro
Erika Trabucco
Michele Messmer Uccelli
Publication date
01-01-2013
Publisher
Current Science Inc.
Published in
Current Neurology and Neuroscience Reports / Issue 1/2013
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-012-0320-5

Other articles of this Issue 1/2013

Current Neurology and Neuroscience Reports 1/2013 Go to the issue

Stroke (HP Adams Jr, Section Editor)

Reversible Cerebral Vasoconstriction Syndrome: A Review of Recent Research

Nerve and Muscle (M Hirano and LH Weimer, Section Editors)

Inclusion Body Myositis

Nerve and Muscle (M Hirano and LH Weimer, Section Editors)

Uses of Skin Biopsy for Sensory and Autonomic Nerve Assessment

Stroke (HP Adams Jr, Section Editor)

Use of Antidepressant Medications To Improve Outcomes After Stroke

Nerve and Muscle (M Hirano and LH Weimer, Section Editors)

Advances in Nerve Repair