“…Prolonged muscle contraction, ischemia/hypoxia, metabolic disorders, and cell stress also lead to increased release of neurotransmitters, inflammatory cytokines, and myokines, which necessary in the pathophysiology of myofascial pain [2,25,31]. Damage to these muscles cause the release of neuropeptides, cytokines, and inflammatory substances such as potassium, bradykinin, cytokines, tumor necrosis factor, interleukin 1β, norepinephrine, protons, prostaglandins, ATP and substances P that can stimulate nociceptors in the muscle thereby releasing CGRP (calcitonin gene-related peptide) [2,8,9,15,18,25]. Mast cells will be degranulated by substance P and release serotonin, histamine, and upregulation of anti-inflammatory cytokines (IL-4 and IL-10) and also the pro-inflammatory factors (TNF-α and IL-6).…”