Hydrogen sulfide as a novel nociceptive messenger

Hydrogen sulfide (H 2S), an endogenous gasotransmitter, modulates various biological events such as inflammation in the mammalian body. The present study investigated possible involvement of H 2S in peripheral nociceptive processing. Intraplantar (i.pl.) administration of NaHS, a H 2S donor, produced prompt hyperalgesia in rats, accompanied by expression of Fos in the spinal dorsal horn. The H 2S-evoked hyperalgesia was blocked by 5,5′-dithio-bis-(2-nitrobenzoic acid) (DTNB), an oxidizing agent, or ethosuximide and mibefradil, T-type Ca 2+ channel inhibitors. l-Cysteine, an endogenous source for H 2S, given i.pl., also elicited hyperalgesia, an effect being abolished by dl-propargylglycine (PPG) and β-cyanoalanine (BCA), inhibitors of cystathionine-γ-lyase, a H 2S synthesizing enzyme. PPG and/or BCA partially inhibited the hyperalgesia induced by i.pl. lipopolysaccharide, an effect being reversed by i.pl. NaHS. In the patch-clamp study using undifferentiated NG108-15 cells that express T-type, but not other types, of Ca 2+ channels, NaHS enhanced the currents through the T-type channels, an effect being blocked by DTNB. Thus, H 2S appears to function as a novel nociceptive messenger through sensitization of T-type Ca 2+ channels in the peripheral tissues, particularly during inflammation.