Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH (N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula. Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.
Introduction: Chronic back pain is one of the most important socioeconomic problems that affects the global population. Elevated levels of inflammatory mediators, such as cytokines, have been correlated with pain, but their role in chronic back pain remains unclear. The effectiveness of anti-inflammatory drugs seems to be limited for chronic back pain. The authors wanted to investigate the levels of inflammatory mediators in long-term medically treated patients with persistent chronic back pain. Methods: Cytokine plasma levels of patients with chronic back pain (n=23), compared to pain-free healthy controls (n=30), were investigated by immunoassay. Patients with chronic back pain were exposed to long-term conservative medical therapy with physiotherapy and anti-inflammatories, also combined with antidepressants and/or muscle-relaxants. Results: The patients with chronic back pain expressed lower levels of the chemokines MCP1, CCL5, and CXCL6 compared to pain-free healthy controls. Significantly lower concentrations of the anti-inflammatory cytokines, interleukin (IL)-4 and granulocyte-colony stimulating factor were also found. Interestingly, levels of proinflammatory cytokines (IL-2, IL-6, IL-1β, tumor necrosis factor alpha), IL-10, granulocyte-macrophage colony-stimulating factor, and stromal cell-derived factor 1 alpha showed no significant differences between both groups. Conclusion: This decrease of inflammatory mediators in medically treated patients with chronic back pain is of unclear origin and might be either a long-term side effect of medical therapy or related to chronic pain. Further longitudinal research is necessary to elucidate the underlying cause of these findings.