Targeting voltage-gated sodium channels for treatment for chronic visceral pain

Figure 3 Possible mechanisms underlying the modulation of voltage-gated sodium channel activity. Inflammatory mediators such as nerve growth factor (NGF), prostaglandin (PG) E2, interleukin (IL)-1β may sensitize sodium channels by different intracellular signal transduction pathways such as protein kinase A (PKA), protein kinase C (PKC), mitogen-activated protein kinase and calmodulin (CaM). In addition, a recent study showed that aquaporin (AQP)-1 directly interacted with the sodium channel, thus contributing to the perception of pain[48]. TTX: Tetrodotoxin; LIF: leukemia inhibitory factor; Trk: Tyrosine receptor kinase; TNF: Tumor necrosis factor; TRAF: Tumor necrosis factor receptor-associated factor; TRADD: TNF receptor-associated death domain protein.