Magnetic resonance spectroscopy across chronic pain disorders: a systematic review protocol synthesising anatomical and metabolite findings in chronic pain patients

BACKGROUND: Chronic pain is pain greater than 3 months duration that may result from disease, trauma, surgery, or unknown origin. The overlap between the psychological, behavioural, and management aspects of pain suggest that limbic brain neurochemistry plays a role in chronic pain pathology. Proton magnetic resonance spectroscopy ((1)H-MRS) can evaluate in vivo brain metabolites including creatine, N-acetylaspartate, myo-inositol, choline, glutamate, glutamine, and gamma-aminobutyric acid in chronic pain; however, a comprehensive systemic review of metabolite expression patterns across all brain areas has yet to be performed. METHODS AND ANALYSIS: Online databases including PubMed/MEDLINE, Google Scholar, EMBASE, the Cochrane Library, OVID, and PsycINFO will be searched for articles relating to (1)H-MRS and chronic pain. Study inclusion criteria will include ages of between 18 and 65 years with a definite diagnosis of chronic pain, no comorbidities, clearly stated brain volumes of interest, and imaging protocols, with comparisons to healthy controls. Two reviewers will extract data relating to volumes of interest, metabolites, study participant demographics, diagnostic method and pain scores, treatments and duration of treatment, scanner information, (1)H-MRS acquisition protocols, and spectral processing software. Where possible, volumes of interest will be reassigned as regions of interest consistent with known regional anatomical and functional properties to increase the power and relevance of the analysis. Statistical analyses will then be conducted using STATA. A central common pathway may exist for chronic pain due to the behavioural manifestations and management similarities between its different types. The goal of this systemic review is to generate a comprehensive neurochemical theory of chronic pain in different brain compartments. SYSTEMATIC REVIEW REGISTRATION: This study is registered with PROSPERO CRD42018112640.