Differential effects of intraplantar capsazepine and ruthenium red on capsaicin-induced desensitization in mice.
Intraplantar injection of capsaicin (1.6 microg/paw) into the mouse hindpaw produced an acute paw-licking/biting response. This study was designed (1) to investigate the antinociceptive effects of intraplantar administration of capsazepine, a competitive vanilloid receptor antagonist, and ruthenium red, a noncompetitive antagonist, in the nociceptive licking/biting response induced by intraplantar injection of capsaicin, and (2) to determine whether these compounds were able to prevent capsaicin-induced desensitization in mice. Both capsazepine and ruthenium red produced a dose-dependent reduction in the capsaicin-induced nociceptive response. In licking/biting response to intraplantar capsaicin, ruthenium red was more potent than capsazepine in producing antinociceptive activity as assayed by the capsaicin test. The first injection of capsaicin induced a profound desensitization to the second and third injections of capsaicin at the interval of 15 or 30 min. The capsaicin-induced desensitization was prevented dose-dependently by antinociceptive doses of capsazepine, whereas ruthenium red in doses exhibiting antinociceptive activity was without effect on capsaicin-induced desensitization. The present results suggest that both capsazepine and ruthenium red can produce a local peripheral antinociceptive action, which may be mediated by inhibiting the membrane ion channel activated by capsaicin. In addition, these data suggest that capsazepine may act in the mechanism clearly different from ruthenium red in the capsaicin-induced nociceptive desensitization.
Sakurada
Tsukasa
T
Department of Biochemistry, Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan. tsukasa@daiichi-cps.ac.jp
Matsumura
Toshihiro
T
Moriyama
Tomoko
T
Sakurada
Chikai
C
Ueno
Shinya
S
Sakurada
Shinobu
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005528:Foot; D007267:Injections; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced* / Q000523:psychology; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D012430:Ruthenium Red / Q000494:pharmacology*
D011955:Receptors, Drug; D012430:Ruthenium Red; C071423:capsazepine; D002211:Capsaicin