Hydrogen sulfide as a novel nociceptive messenger.
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.
Kawabata
Atsufumi
A
Division of Physiology and Pathophysiology, Department of Pharmacy, School of Pharmacy, Kinki University, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
Ishiki
Tsuyoshi
T
Nagasawa
Keita
K
Yoshida
Shigeru
S
Maeda
Yumi
Y
Takahashi
Tomoko
T
Sekiguchi
Fumiko
F
Wada
Tetsuyuki
T
Ichida
Seiji
S
Nishikawa
Hiroyuki
H
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
D020747:Calcium Channels, T-Type; D006862:Hydrogen Sulfide