The latter theory may be supported by our surprising findings that the observed TH17/Treg imbalance persisted despite clinical improvement after multimodal therapy even after a follow-up period of 6 months. In summary, we found a persisting TH17/Treg imbalance with an increased count of anti-inflammatory Tregs and a decreased number of pro-inflammatory TH17 cells in peripheral blood of CLBP patients pointing to a strong association between chronic pain and immune suppression rather than immune activation. Importantly, these findings are not reflected by serum cytokine concentration, indicating a major role of specific T cell subset measurements in the analysis of pain-related immune responses. Taken together, the results of the current study suggest an involvement of TH17/Treg in the pathogenesis of CLBP and emphasize the importance of these cells in the crosstalk of pain and immune response. Cell locomotion may be navigated by gradients of soluble factors. Similar to chemotaxis by microorganisms, chemotactic Dantrolene sodium hemiheptahydrate migrations by neuronal cells or neutrophils can be desensitized in the constant presence of a chemo-attractant. To restart the inactivated guidance, the cell needs to periodically sample the concentration of chemo-attractant and integrate this with the signaling processes so that it resets the cell movement according to the environmental change. In addition to soluble chemo-attractants, the chemistry and topography of a Dopamine HCl growth substrate to which the cells have attached can also control cell motility. For example, at the boundary of different extracellular matrix coatings, cells tend to differentiate and selectively adhere to the area where the preferred ECM molecules reside. On a substrate fabricated with a gradient of growthpromoting ECM, neuronal growth cones can navigate up the concentration gradient. However, in all these experimental settings, there has been no clear answer as to whether or not ECM-guided motility can become adaptive and if so, how can the desensitized ECM-guidance be reactivated.Here, we grow fish keratocytes onto substrates that are coated with micro-scaled paths of fibronectin, which enables us to assess ECM navigation by analyzing different motile behaviors as the cells crawling along or across the FBN paths.