Colonic Hydrogen Sulfide–Induced Visceral Pain and Referred Hyperalgesia Involve Activation of Both Ca_v3.2 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 Ca_v3.2. 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 Ca_v3.2 and TRPA1 channels in mice.