Pathophysiology of cation channels in pain: Focus on TRP Channels

Abstract

In neurons such as dorsal root ganglion (DRG) and trigeminal ganglia, calcium (Ca2+) and sodium ion concentrations are higher in in outside than in cytosol, although potassium ion concentration was higher in inside of the neurons than outside of the neurons. Within the ions, it has been suggested that a dysregulation of Ca2+ homeostasis acts a key role in the pathogenesis of oxidative stress associated nerve damage. Ca2+ is a main intracellular messenger involved in several physiological functions of neurons such survival, death, synaptic plasticity and neurotransmitter release. It has specific role in induction of peripheral pain. Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. The TRP superfamily is containing 6 subfamilies with 28 members in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the voltage gated calcium channels. Some TRP channels such as TRP melastatin 2 (TRPM2), melastatin 7 (TRPM7) and TRP ankyrin 1 (TRPA1) are activated by oxidative stress. Expression levels of TRPA1, TRPM2 and TRPM7 are high in DRG, phagocytic cells and hippocampus, respectively. Therefore, TRPM2 is important channels in physiological activity of phagocytic cells such as neutrophil and monocytes (Heiner et al. 2006). TRPM7 and TRPA1 have main roles in cerebral ischemia and peripheral pain molecular pathways, respectively (Carrasco et al. 2018; Sun, 2017). Till today specific antagonists of most TRP channels have not been discovered yet and they have potential targets for discovering drugs in neuroscience. In pain etiology, Ca2+ is important and it has been demonstrated in some studies that the administration of an antagonist to Ca2+ channels induces a reduction in chemotherapeutic  agents-induced neuropathic pain.  In the presentation, I discussed novel results of Ca2+ on the peripheral pain by the regulation of TRP channels.  I concluded that the results of recent studies suggest that increased cytosolic Ca2+ has through inhibition of TRP channels main role in etiology of peripheral pain. It seems to that the TRP channels are potential target for treatment of peripheral pain.