title: Pain in multiple sclerosis: a systematic review of neuroimaging studies.
abstract: BACKGROUND
  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.
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, UK ; Department of Experimental Biology, Faculty of Medicine, Porto University, Portugal ; Nuffield Division Anaesthetics, Nuffield Department of Clinical Neurosciences, University of Oxford, UK ; IBMC - Instituto de Biologia Molecular e Celular, Porto University, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Seixas
authors.affiliation: Department of Clinical Neurosciences, University of Edinburgh, UK ; Department of Palliative Medicine, University of Edinburgh, UK.
authors.forename: P
authors.initials: P
authors.lastname: Foley
authors.affiliation: Division of Clinical Neurology, University of Oxford, UK ; Oxford Radcliffe Hospitals NHS Trust, UK.
authors.forename: J
authors.initials: J
authors.lastname: Palace
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, Porto University, Portugal ; IBMC - Instituto de Biologia Molecular e Celular, Porto University, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Lima
authors.affiliation: Department of Radiology, Centro Hospitalar São João, Portugal ; Medical Imaging Group, Faculty of Medicine, Porto University, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Ramos
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, UK ; Nuffield Division Anaesthetics, Nuffield Department of Clinical Neurosciences, University of Oxford, UK.
authors.forename: I
authors.initials: I
authors.lastname: Tracey
mesh_terms: D006801:Humans; D009103:Multiple Sclerosis / Q000150:complications* / Q000503:physiopathology; D059906:Neuroimaging; D010146:Pain / Q000209:etiology* / Q000503:physiopathology
keywords: Headache; Magnetic resonance imaging; Multiple sclerosis; Pain; Review