title: Hydrogen sulfide as a novel nociceptive messenger.
abstract: Hydrogen sulfide (H(2)S), an endogenous gasotransmitter, modulates various biological events such as inflammation in the mammalian body. The present study investigated possible involvement of H(2)S in peripheral nociceptive processing. Intraplantar (i.pl.) administration of NaHS, a H(2)S donor, produced prompt hyperalgesia in rats, accompanied by expression of Fos in the spinal dorsal horn. The H(2)S-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(2)S, given i.pl., also elicited hyperalgesia, an effect being abolished by DL-propargylglycine (PPG) and beta-cyanoalanine (BCA), inhibitors of cystathionine-gamma-lyase, a H(2)S 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(2)S appears to function as a novel nociceptive messenger through sensitization of T-type Ca(2+) channels in the peripheral tissues, particularly during inflammation.
authors.affiliation: Division of Physiology and Pathophysiology, Department of Pharmacy, School of Pharmacy, Kinki University, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishiki
authors.forename: Keita
authors.initials: K
authors.lastname: Nagasawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Yumi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takahashi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Wada
authors.forename: Seiji
authors.initials: S
authors.lastname: Ichida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D020747:Calcium Channels, T-Type; D006862:Hydrogen Sulfide