Effect of spinal nitric oxide inhibition on capsaicin-induced nociceptive response.
Pretreatment with the nitric oxide synthase (NOS) inhibitor L-NG-nitro arginine methyl ester (L-NAME), injected intraperitoneally (i.p.) or intrathecally (i.t.), produced a significant antinociception in the mouse assessed by the capsaicin-induced paw licking procedure. Varying the administration time of an effective dose of L-NAME (160nmol, i.t.) resulted in a significant decrease of the brief nociceptive behavioral response induced by capsaicin, even when L-NAME was given 2 hr before capsaicin. L-NAME, injected i.p. or i.t., produced a dose-related reduction in paw licking in the second phase of the formalin (2.0%) response without affecting the first phase. L-Arginine (600 mg/kg, i.p.) but not D-arginine (600 mg/kg, i.p.) reversed the antinociceptive effect of L-NAME in the capsaicin test. Antinociceptive effect of L-NAME, injected i.p. or i.t., was more potent in the second phase response of formalin-induced paw licking than in capsaicin-induced nociceptive response. The inhibitory action of L-NAME was reversed by L-arginine but not D-arginine in the second phase response. L-Arginine alone was without affecting capsaicin- and formalin-induced nociceptive responses. These results suggest that spinal nitric oxide (NO) may be involved in the mechanisms of capsaicin-induced brief nociceptive stimuli, but not in the first, acute phase of the formalin-induced response in mice.
Sakurada
T
T
Department of Biochemistry, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan.
Sugiyama
A
A
Sakurada
C
C
Tan-No
K
K
Yonezawa
A
A
Sakurada
S
S
Kisara
K
K
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D005557:Formaldehyde / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000201:enzymology*; D013237:Stereoisomerism
D005557:Formaldehyde; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester