Colonic Hydrogen Sulfide–Induced Visceral Pain and Referred Hyperalgesia Involve Activation of Both Cav3.2 and TRPA1 Channels in Mice

Abstract

Luminal hydrogen sulfide (H2S), a gasotransmitter, causes colonic pain / referred hyperalgesia in mice, most probably via activation of T-type Ca2+ channels. Here we analyzed the mechanisms for H2S-induced facilitation of colonic pain signals. Intracolonic administration of NaHS, an H2S donor, evoked visceral pain−like nociceptive behavior and referred hyperalgesia in mice, an effect abolished by NNC 55-0396, a selective T-type Ca2+-channel blocker, or by knockdown of Cav3.2. AP18, a TRPA1 blocker, also prevented the NaHS-induced colonic pain and referred hyperalgesia. These findings demonstrate that H2S-induced colonic pain and referred hyperalgesia require activation of both Cav3.2 and TRPA1 channels in mice. Keywords:: hydrogen sulfide, T-type calcium channel, TRPA1