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Fibromyalgia is characterized by chronic pain and a striking discrepancy between objective signs of tissue damage and severity of pain. Function and structural alterations in brain areas involved in pain processing may explain this feature. Previous case-control studies in fibromyalgia focused on acute pain processing using experimentally-evoked pain paradigms. Yet, these studies do not allow conclusions about chronic, stimulus-independent pain. Resting-state cerebral blood flow (rsCBF) acquired by arterial spin labelling (ASL) may be a more accurate marker for chronic pain. The objective was to integrate four different functional and structural neuroimaging markers to evaluate the neural correlate of chronic, stimulus-independent pain using a resting-state paradigm. In line with the pathophysiological concept of enhanced central pain processing we hypothesized that rsCBF is increased in fibromyalgia in areas involved in processing of acute pain. We performed an age matched case-control study of 32 female fibromyalgia patients and 32 pain-free controls and calculated group differences in rsCBF, resting state functional connectivity, grey matter volume and cortical thickness using whole-brain and region of interest analyses. We adjusted all analyses for depression and anxiety. As centrally acting drugs are likely to interfere with neuroimaging markers, we performed a subgroup analysis limited to patients not taking such drugs. We found no differences between cases and controls in rsCBF of the thalamus, the basal ganglia, the insula, the somatosensory cortex, the prefrontal cortex, the anterior cingulum and supplementary motor area as brain areas previously identified to be involved in acute processing in fibromyalgia. The results remained robust across all neuroimaging markers and when limiting the study population to patients not taking centrally acting drugs and matched controls. In conclusion, we found no evidence for functional or structural alterations in brain areas involved in acute pain processing in fibromyalgia that could reflect neural correlates of chronic stimulus-independent pain.

BackgroundMetamizole is used to treat pain in many parts of the world. Information on the safety profile of metamizole is scarce; no conclusive summary of the literature exists.ObjectiveTo determine whether metamizole is clinically safe compared to placebo and other analgesics.MethodsWe searched CENTRAL, MEDLINE, EMBASE, CINAHL, and several clinical trial registries. We screened the reference lists of included trials and previous systematic reviews. We included randomized controlled trials that compared the effects of metamizole, administered to adults in any form and for any indication, to other analgesics or to placebo. Two authors extracted data regarding trial design and size, indications for pain medication, patient characteristics, treatment regimens, and methodological characteristics. Adverse events (AEs), serious adverse events (SAEs), and dropouts were assessed. We conducted separate meta-analyses for each metamizole comparator, using standard inverse-variance random effects meta-analysis to pool the estimates across trials, reported as risk ratios (RRs). We calculated the DerSimonian and Laird variance estimate T2 to measure heterogeneity between trials. The pre-specified primary end point was any AE during the trial period.ResultsOf the 696 potentially eligible trials, 79 trials including almost 4000 patients with short-term metamizole use of less than two weeks met our inclusion criteria. Fewer AEs were reported for metamizole compared to opioids, RR = 0.79 (confidence interval 0.79 to 0.96). We found no differences between metamizole and placebo, paracetamol and NSAIDs. Only a few SAEs were reported, with no difference between metamizole and other analgesics. No agranulocytosis or deaths were reported. Our results were limited by the mediocre overall quality of the reports.ConclusionFor short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics. High-quality, adequately sized trials assessing the intermediate- and long-term safety of metamizole are needed.