Regulation of Ca_v3.2-mediated pain signals by hydrogen sulfide

Abstract

Hydrogen sulfide (H₂S), an endogenous gasotransmitter, is generated from L-cysteine by 3 distinct enzymes including cystathionine-γ-lyase (CSE), and targets multiple molecules, thereby playing various roles in health and disease. H₂S triggers or accelerates somatic pain and visceral nociceptive signals in the pancreas, colon and bladder by enhancing the activity of Ca_v3.2 T-type calcium channels. H₂S also activates TRPA1, which participates in H₂S-induced somatic pain signaling. However, Ca_v3.2 predominantly mediates colonic nociception by H₂S, because genetic deletion of TRPA1 does not reduce H₂S-induced colonic pain. The functional upregulation of the CSE/H₂S/Ca_v3.2 system is involved in neuropathic pain and visceral pain accompanying pancreatitis and cystitis. Ca_v3.2 also appears to participate in irritable bowel syndrome (IBS), although the role of endogenous H₂S generation by CSE in IBS is still open to question. In this review, we describe how H₂S regulates pain signals, particularly by interacting with Ca_v3.2.