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Cited by 61Multiple Sclerosis Research StudiesPain Mechanisms and TreatmentsPain Management and Treatment

Pain in multiple sclerosis: A systematic review of neuroimaging studies

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Seixas, D., Foley, P., Palace, J., Lima, D., Ramos, I., Tracey, I.·2014·NeuroImage: Clinical
DOI 10.1016/j.nicl.2014.06.014PMC PMC4141976
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Abstract

INTRODUCTION: While pain in multiple sclerosis (MS) is common, in many cases the precise mechanisms are unclear. Neuroimaging studies could have a valuable role in investigating the aetiology of pain syndromes. The aim of this review was to synthesise and appraise the current literature on neuroimaging studies of pain syndromes in MS. METHODS: We systematically searched PubMed and Scopus from their inception dates to the 2nd of April 2013. Studies were selected by predefined inclusion and exclusion criteria. Methodological quality was appraised. Descriptive statistical analysis was conducted. RESULTS: We identified 38 studies of variable methodology and quality. All studies but one used conventional structural magnetic resonance imaging, and the majority reported a positive association between location of demyelinating lesions and specific neuropathic pain syndromes. Most investigated headache and facial pain, with more common pain syndromes such as limb pain being relatively understudied. We identified a number of methodological concerns, which along with variable study design and reporting limit our ability to synthesise data. Higher quality studies were however less likely to report positive associations of lesion distribution to pain syndromes. CONCLUSIONS: Further high quality hypothesis-driven neuroimaging studies of pain syndromes in MS are required to clarify pain mechanisms, particularly for the commonest pain syndromes.

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  • Determining whether lesions are neuroanatomically plausible for explaining pain in multiple sclerosis is complex, as the correlation between lesion location and pain is at best moderate-to-good.

    “However, determining whether lesions are neuroanatomically plausible for explaining pain in MS is complex, as the correlation between lesion location and pain is at best moderate‐to‐good (Ismail et al. 2025; Ouyang et al. 2024; Seixas et al. 2014; Svendsen et al. 2011).”

    From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the <scp>NeuPSIG</scp> Algorithm (2026) · cites this paper as Seixas et al. 2014

    The Discussion says identifying culprit lesions often relied on anatomical assumptions, with few studies checking whether lesion timing matched pain onset. The Conclusion reports differing findings across studies and fewer positive associations in higher-quality studies. These passages support the difficulty of linking lesions to pain, but do not characterize the correlation as “moderate-to-good.” Page numbers are unavailable in our copy. (LLM, conf=0.86)

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References 63 · Cited by 61

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  1. Alstadhaug K. Breivik K. Rusic Z. Recurrent headache due to MS plaque Headache 48 2008 453 454 18081822 18081822
  2. Andrade C. Massano J. Guimarães J. Garrett M.C. Stretching the limbs? Tonic spasms in multiple sclerosis BMJ Case Reports 30 2012 23208828 PMC4544469 23208828
  3. 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 British Journal of Neurosurgery 19 2005 463 468 16574557 16574557
  4. Balasa R. Bajko Z. Trigeminal neuralgia in multiple sclerosis patients: a clinical comparison of trigeminal neuralgia in patients with and without underlying multiple sclerosis Romanian Journal of Neurology 9 2010 68 73
  5. Bax L. Moons K.G. Beyond publication bias Journal of Clinical Epidemiology 64 2011 459 462 21194886 21194886
  6. Bentley P.I. Kimber T. Schapira A.H. Painful third nerve palsy in MS Neurology 58 2002 1532 12034792 12034792
  7. 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 55 2004 830 838 15458591 15458591
  8. Burkey A.R. Abla-Yao S. Successful treatment of central pain in a multiple sclerosis patient with epidural stimulation of the dorsal root entry zone Pain Medicine (Malden, Mass.) 11 2010 127 132 20447296 20447296
  9. Campbell P. Wynne-Jones G. Dunn K.M. The influence of informal social support on risk and prognosis in spinal pain: a systematic review European Journal of Pain (London, England) 15 2011 444.e1 444.e14 20970363 PMC3142815 20970363
  10. Carrieri P.B. Montella S. Petracca M. Glossopharyngeal neuralgia as onset of multiple sclerosis Clinical Journal of Pain 25 2009 737 739 19920727 19920727
  11. Compston A. Coles A. Multiple sclerosis Lancet 372 2008 1502 1515 18970977 18970977
  12. Cordella R. Franzini A. La Mantia L. Marras C. Erbetta A. Broggi G. Hypothalamic stimulation for trigeminal neuralgia in multiple sclerosis patients: efficacy on the paroxysmal ophthalmic pain Multiple Sclerosis (Houndmills, Basingstoke, England) 15 2009 1322 1328 19812115 19812115
  13. Cruccu G. Biasiotta A. Di Rezze S. Fiorelli M. Galeotti F. Innocenti P. Mameli S. Millefiorini E. Truini A. Trigeminal neuralgia and pain related to multiple sclerosis Pain 143 2009 186 191 19171430 19171430
  14. Da Silva C.J. da Rocha A.J. Mendes M.F. Maia A.C. Jr. Braga F.T. Tilbery C.P. Trigeminal involvement in multiple sclerosis: magnetic resonance imaging findings with clinical correlation in a series of patients Multiple Sclerosis (Houndmills, Basingstoke, England) 11 2005 282 285 15957508 15957508
  15. Davey R. Al-Din A. Secondary trigeminal autonomic cephalgia associated with multiple sclerosis Cephalalgia: an International Journal of Headache 24 2004 605 607 15196304 15196304
  16. Deppe M. Müller D. Kugel H. Ruck T. Wiendl H. Meuth S.G. DTI detects water diffusion abnormalities in the thalamus that correlate with an extremity pain episode in a patient with multiple sclerosis NeuroImage: Clinical 2 2013 258 262 24179780 PMC3778262
  17. De Santi L. Monti L. Menci E. Bellini M. Annunziata P. Clinical–radiologic heterogeneity of occipital neuralgiform pain as multiple sclerosis relapse Headache 49 2009 304 307 18647183 18647183
  18. Donat J. A patient with cluster headache — due to a brainstem lesion Headache 52 2012 1035 1036 22077341 22077341
  19. Eldridge P.R. Sinha A.K. Javadpour M. Littlechild P. Varma T.R. Microvascular decompression for trigeminal neuralgia in patients with multiple sclerosis Stereotactic and Functional Neurosurgery 81 2003 57 64 14742965 14742965
  20. Filippi M. Rocca M.A. MR imaging of multiple sclerosis Radiology 259 2011 659 681 21602503 21602503
  21. Filippi M. Rocca M.A. Barkhof F. Brück W. Chen J.T. Comi G. DeLuca G. De Stefano N. Erickson B.J. Evangelou N. Fazekas F. Geurts J.J. Lucchinetti C. Miller D.H. Pelletier D. Popescu B.F. Lassmann H. Attendees of the Correlation Between Pathological MRI Findings in MS Workshop Association between pathological and MRI findings in multiple sclerosis Lancet Neurology 11 (2012) 349–360 [Pubmed: 22441196] 22441196
  22. Fragoso Y.D. Brooks J.B. Two cases of lesions in brainstem in multiple sclerosis and refractory migraine Headache 47 2007 852 854 17578534 17578534
  23. Gass A. Kitchen N. MacManus D.G. Moseley I.F. Hennerici M.G. Miller D.H. Trigeminal neuralgia in patients with multiple sclerosis: lesion localization with magnetic resonance imaging Neurology 49 1997 1142 1144 9339705 9339705
  24. Ge Y. Law M. Johnson G. Herbert J. Babb J.S. Mannon L.J. Grossman R.I. Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis lesions: characterizing hemodynamic impairment and inflammatory activity AJNR. American Journal of Neuroradiology 26 2005 1539 1547 15956527 15956527 PMC8149080
  25. 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 2005 670 677 15953299 15953299
  26. Gentile S. Ferrero M. Vaula G. Rainero I. Pinessi L. Cluster headache attacks and multiple sclerosis Journal of Headache and Pain 8 2007 245 247 17901919 17901919 PMC3451675
  27. Geurts J.J. Pouwels P.J. Uitdehaag B.M. Polman C.H. Barkhof F. Castelijns J.A. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging Radiology 236 2005 254 260 15987979 15987979
  28. González-Quintanilla V. Oterino A. Toriello M. de Pablos C. Wu Y. de Marco E. Pascual J. Cluster-tic syndrome as the initial manifestation of multiple sclerosis Journal of Headache and Pain 13 2012 425 429 22543446 22543446 PMC3381064
  29. Haas D.C. Kent P.F. Friedman D.I. Headache caused by a single lesion of multiple sclerosis in the periaqueductal gray area Headache 33 1993 452 455 8262789 8262789
  30. Headache Classification Committee of the International Headache Society Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain Cephalalgia 8 1988 1 96 3048700
  31. Headache Classification Subcommittee of the International Headache Society The International Classification of Headache Disorders: 2nd edition Cephalalgia: an International Journal of Headache 24 2004 9 160 14979299 14979299
  32. Hellwig K. Lukas C. Brune N. Schimrigk S. Przuntek H. Müller T. Repeat intrathecal triamcinolone acetonide application reduces acute occurring painful dysesthesia in patients with relapsing remitting multiple sclerosis TheScientificWorldJournal 6 2006 460 465 16604259 PMC5917289 16604259
  33. Inglese M. Park S.J. Johnson G. Babb J.S. Miles L. Jaggi H. Herbert J. Grossman R.I. Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T Archives of Neurology 64 2007 196 202 17296835 17296835
  34. Kalia L.V. O'Connor P.W. Severity of chronic pain and its relationship to quality of life in multiple sclerosis Multiple Sclerosis (Houndmills, Basingstoke, England) 11 2005 322 327 15957515 15957515
  35. Kister I. Caminero A.B. Monteith T.S. Soliman A. Bacon T.E. Bacon J.H. Kalina J.T. Inglese M. Herbert J. Lipton R.B. Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course Journal of Headache and Pain 11 2010 417 425 20625916 20625916 PMC3452278
  36. Leandri M. Cruccu G. Gottlieb A. Cluster headache-like pain in multiple sclerosis Cephalalgia: an International Journal of Headache 19 1999 732 734 10570729 10570729
  37. Liu F.C. Fuh J.L. Wang S.J. Symptomatic trigeminal autonomic cephalalgia associated with allodynia in a patient with multiple sclerosis Journal of the Chinese Medical Association: JCMA 71 2008 583 586 19015058 19015058
  38. McDonald W.I. Compston A. Edan G. Goodkin D. Hartung H.P. Lublin F.D. McFarland H.F. Paty D.W. Polman C.H. Reingold S.C. Sandberg-Wollheim M. Sibley W. Thompson A. van den Noort S. Weinshenker B.Y. Wolinsky J.S. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis Annals of Neurology 50 2001 121 127 11456302 11456302
  39. Meaney J.F. Watt J.W. Eldridge P.R. Whitehouse G.H. Wells J.C. Miles J.B. Association between trigeminal neuralgia and multiple sclerosis: role of magnetic resonance imaging Journal of Neurology, Neurosurgery, and Psychiatry 59 1995 253 259 7673952 PMC486023 7673952
  40. Minagar A. Sheremata W.A. Glossopharyngeal neuralgia and MS Neurology 54 2000 1368 1370 10746612 10746612
  41. 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 Archives of Neurology 58 2001 101 104 11176942 11176942
  42. 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 2008 96 111 17928147 17928147
  43. Pichiecchio A. Bergamaschi R. Tavazzi E. Romani A. Todeschini A. Bastianello S. Bilateral trigeminal enhancement on magnetic resonance imaging in a patient with multiple sclerosis and trigeminal neuralgia Multiple Sclerosis (Houndmills, Basingstoke, England) 13 2007 814 816 17613612 17613612
  44. Poldrack R.A. Fletcher P.C. Henson R.N. Worsley K.J. Brett M. Nichols T.E. Guidelines for reporting an fMRI study NeuroImage 40 2008 409 414 18191585 18191585 PMC2287206
  45. Polman C.H. Reingold S.C. Banwell B. Clanet M. Cohen J.A. Filippi M. Fujihara K. Havrdova E. Hutchinson M. Kappos L. Lublin F.D. Montalban X. O'Connor P. Sandberg-Wollheim M. Thompson A.J. Waubant E. Weinshenker B. Wolinsky J.S. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria Annals of Neurology 69 2011 292 302 21387374 21387374 PMC3084507
  46. McDonald W.I. Compston A. Edan G. Goodkin D. Hartung H.P. Lublin F.D. McFarland H.F. Paty D.W. Polman C.H. Reingold S.C. Sandberg-Wollheim M. Sibley W. Thompson A. van den Noort S. Weinshenker B.Y. Wolinsky J.S. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis Annals of Neurology 50 2001 121 127 11456302 11456302
  47. Ramirez-Lassepas M. Tulloch J.W. Quinones M.R. Snyder B.D. Acute radicular pain as a presenting symptom in multiple sclerosis Archives of Neurology 49 1992 255 258 1536627 1536627
  48. Poser C.M. Paty D.W. Scheinberg L. McDonald W.I. Davis F.A. Ebers G.C. Johnson K.P. Sibley W.A. Silberberg D.H. Tourtellotte W.W. New diagnostic criteria for multiple sclerosis: guidelines for research protocols Annals of Neurology 13 1983 227 231 6847134 6847134
  49. Rose A.S. Ellison G.W. Myers L.W. Tourtellotte W.W. Criteria for the clinical diagnosis of multiple sclerosis Neurology 26 1976 20 22 58393 58393
  50. Svendsen K.B. Sørensen L. Jensen T.S. Hansen H.J. Bach F.W. MRI of the central nervous system in MS patients with and without pain European Journal of Pain (London, England) 15 2011 395 401 20947397 20947397
  51. Tanei T. Kajita Y. Wakabayashi T. Motor cortex stimulation for intractable neuropathic facial pain related to multiple sclerosis Neurologia Medico-Chirurgica 50 2010 604 607 20671392 20671392
  52. Tortorella P. Rocca M.A. Colombo B. Annovazzi P. Comi G. Filippi M. Assessment of MRI abnormalities of the brainstem from patients with migraine and multiple sclerosis Journal of the Neurological Sciences 244 2006 137 141 16530789 16530789
  53. Tosi L. Righetti C.A. Zanette G. Beltramello A. A single focus of multiple sclerosis in the cervical spinal cord mimicking a radiculopathy Journal of Neurology, Neurosurgery, and Psychiatry 64 1998 277 9489549 PMC2169945 9489549
  54. Tracey I. Neuroimaging of pain mechanisms Current Opinion in Supportive and Palliative Care 1 2007 109 116 18685351 18685351
  55. Vandenbroucke J.P. In defense of case reports and case series Annals of Internal Medicine 134 2001 330 334 11182844 11182844
  56. Vilisaar J. Constantinescu C.S. SUNCT in multiple sclerosis Cephalalgia: an International Journal of Headache 26 2006 891 893 16776709 16776709
  57. Wise R.G. Tracey I. The role of fMRI in drug discovery Journal of Magnetic Resonance Imaging: JMRI 23 2006 862 876 16649197 16649197
  58. Yetimalar Y. Seçil Y. Inceoglu A.K. Eren S. Başoğlu M. Unusual primary manifestations of multiple sclerosis New Zealand Medical Journal 121 2008 47 59 18677330 18677330

Authors
Seixas, D., Foley, P., Palace, J., Lima, D., Ramos, I., & Tracey, I.
Affiliations
  • Universidade do Porto (PT)
  • University of Edinburgh (GB)
  • John Radcliffe Hospital (GB)
  • University of Oxford (GB)
Corresponding author
Seixas, D.
ORCID
Venue
NeuroImage: Clinical
Publisher
Elsevier BV
Published
2014
Volume
5
Pages
322-331
ISSN
2213-1582 (ISSN-L)
DOI
10.1016/j.nicl.2014.06.014
PMC
PMC4141976
OpenAlex
W2054556815
Cited by
61
References
63
Citations by year
2026: 5 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 3
FWCI
0.76
Type
journal article
Language
en
Open access
Licence
Locations
  • NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Fundação para a Ciência e a Tecnologia (SFRH/BD/27411/2006)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Keywords
multiple sclerosis, neuropathic pain, pain mechanisms, demyelinating lesions, lesion distribution, headache, facial pain, limb pain, structural MRI, pain syndromes
MeSH terms
Humans, Multiple Sclerosis, Pain, Neuroimaging

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