Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia.

The effect of inhibition of nitric oxide synthase (NOS) on hindpaw hyperalgesia (assessed using mechanical and thermal noxious stimuli) and oedema formation following intraplantar injection of carrageenan (150 microl, 2% w v(-1)) in the rat was determined. For this purpose, NOS inhibitors including L-N(G) nitro-arginine methyl ester (L-NAME; isoform non-selective NOS inhibitor), 7-nitroindazole (7-NI) and 1-(2-trifluoromethylphenyl) imidazole (TRIM; both relatively selective inhibitors of neuronal NOS) were used. Mechanical/thermal nociceptive threshold values and hindpaw weight were recorded prior to and 3 h after administration of carrageenan. NOS inhibitors (5-25 mg kg(-1), i.p.) were administered 2.5 h after carrageenan. L-NAME, 7-NI and TRIM inhibited carrageenan-induced mechanical and thermal hyperalgesia. Calculated ED50 values (micromol kg(-1), i.p.) were 63.4, 96.2 and 92.7 (mechanical) and 42.2, 53.9 and 62.1 (thermal), respectively. None of the drugs affected pain perception in the non-injected hindpaw or carrageenan-induced hindpaw weight gain. Thus, 7-NI and TRIM, at doses previously reported not to influence cardiovascular haemodynamics, inhibit hyperalgesia in the rat regardless of the type of noxious stimulus employed. Accordingly, selective inhibitors of neuronal NOS may prove useful for the treatment of prolonged pain in man.