Chronic low back pain (CLBP) is a leading cause of disability and costs in health care systems worldwide. Despite extensive research, the exact pathogenesis of CLBP, particularly the individual risk of chronification remains unclear. To investigate a possible role of the adaptive immune system in the pathophysiology of CLBP, we analyzed T cell related cytokine profiles, T cell related mRNA expression patterns and the distribution of T cell subsets in 37 patients suffering from nonspecific CLBP before and after multimodal therapy in comparison to 25 healthy controls. Serum patterns of marker cytokines were analyzed by Luminex technology, mRNA expression of cytokines and specific transcription factors was measured by real-time PCR, and distribution of TH1-, TH2-, TH17- and regulatory T cell (Tregs) subsets was determined by multicolor flow cytometry. We found that CLBP patients exhibit an increased number of anti-inflammatory Tregs, while pro-inflammatory TH17 cells are decreased, resulting in an altered TH17/Treg ratio. Accordingly, FoxP3 and TGF-β-mRNA expression was elevated, while expression of IL-23 was reduced. Serum cytokine analyses proved to be unsuitable to monitor the adaptive immune response in CLBP patients. We further show that even after successful therapy with lasting reduction of pain, T cell subset patterns remained altered after a follow-up period of 6 months. These findings suggest an involvement of TH17/Treg cells in the pathogenesis of CLBP and emphasize the importance of these cells in the crosstalk of pain and immune response.Trial RegistrationGerman Clinical Trial Register: Registration Trial DRKS00005954.
Direct intercellular communication via gap junctions has an important role in the development of the nervous system, ranging from cell migration and neuronal differentiation to the formation of neuronal activity patterns. This study characterized and compared the specific spatio-temporal expression patterns of connexins (Cxs) 37, 43 and 45 during early human developmental stages (since the 5th until the 10th developmental week) in the spinal cord (SC) and dorsal root ganglia (DRG) using double immunofluorescence and transmission electron microscopy. We found the expression of all three investigated Cxs during early human development in all the areas of interest, in the SC, DRG, developing paravertebral ganglia of the sympathetic trunk, notochord and all three meningeal layers, with predominant expression of Cx37. Comparing the expression of different Cxs between distinct developmental periods, we did not find significant differences. Specific spatio-temporal pattern of Cxs expression might reflect their relevance in the development of all areas of interest via cellular interconnectivity and synchronization during the late embryonic and early fetal period of human development.
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