Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in nociception/hyperalgesia elicited by protease-activated receptor-2 activation in mice and rats.
Activation of the peripheral protease-activated receptor-2 (PAR-2) triggers nociceptive behaviour and thermal hyperalgesia in rats. The present study created a novel mouse model for PAR-2-triggered nociception, and then examined the roles of NMDA receptors and the nitric oxide (NO) pathway in nociceptive processing by PAR-2. Intraplantar administration of the PAR-2 agonist SLIGRL-NH(2) elicited nociceptive responses in mice, an effect being more specific in mast cell-depleted mice. This PAR-2-triggered nociception was abolished by the NMDA receptor antagonist MK-801, but not the neuronal NO synthase inhibitor 7-nitro indazole. In contrast, the PAR-2-triggered thermal hyperalgesia in rats was blocked by both agents. Our study thus provides a novel mouse model for PAR-2-mediated nociception, and suggests that NMDA receptors are involved in PAR-2-triggered nociception and hyperalgesia, while NO contributes only to the latter.
Department of Pathophysiology and Therapeutics, School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
Atsufumi
A
Kawabata
Naoyuki
N
Kawao
Hideki
H
Itoh
Chiho
C
Shimada
Kaori
K
Takebe
Ryotaro
R
Kuroda
Takashi
T
Masuko
Kazuo
K
Kataoka
Shinji
S
Ogawa
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D044464:Receptor, PAR-2; D016194:Receptors, N-Methyl-D-Aspartate; D018179:Receptors, Thrombin; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; C080122:7-nitroindazole