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at the same time, changes in intracellular Ca 2+ lead to the opening of neuronal pannexin 1 channels to open and activate cystatinase 1, followed by the release of high mobility group box-1 protein and the activation of nuclear factor kappa-B signaling pathway in astrocytes (Karatas et al., 2013), which triggers substantial inflammatory response, producing a variety of inflammatory cytokines such as interleukin (IL)-1 (Ghaemi et al., 2018), IL-6 (Ghaemi et al., 2018) and tumor necrosis factor (TNF)- (Ghaemi et al., 2018) as well as Toll-like receptor (Ghaemi et al., 2016) production, which prolongs trigeminal nerve stimulation, leading to sensitization of the dura mater and triggering of headache (Figure 1B)
This includes patients with acute muscle strains, tendon irritation, ligament sprains, plantar fascia irritation, Achilles tendinopathy, patellar tendinopathy, rotator cuff irritation, tennis elbow, golfers elbow, or localized joint-adjacent soft-tissue pain
Most chronic diseases are related to oxidative stress arising from the affected tissue losing the capacity to maintain glutathione at adequate healthy levels
