[Regulation of Ca3.2-mediated pain signals by hydrogen sulfide].

Hydrogen sulfide (HS), 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. HS triggers or accelerates somatic pain and visceral nociceptive signals in the pancreas, colon and bladder by enhancing the activity of Ca3.2 T-type calcium channels. HS also activates TRPA1, which participates in HS-induced somatic pain signaling. However, Ca3.2 predominantly mediates colonic nociception by HS, because genetic deletion of TRPA1 does not reduce HS-induced colonic pain. The functional upregulation of the CSE/HS/Ca3.2 system is involved in neuropathic pain and visceral pain accompanying pancreatitis and cystitis. Ca3.2 also appears to participate in irritable bowel syndrome (IBS), although the role of endogenous HS generation by CSE in IBS is still open to question. In this review, we describe how HS regulates pain signals, particularly by interacting with Ca3.2.