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.