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 hyp eralgesia (assessed using mechanical and thermal noxious stimuli) and oedema formation following intraplantar injection of carrageenan (150 mu l, 2% w v(-1)) in the rat was determined. For this purpose, NOS inh ibitors including L-NG nitro-arginine methyl ester (L-NAME; isoform no n-selective NOS inhibitor), 7-nitroindazole (7-NI) and 1-(2-trifluorom ethylphenyl) imidazole (TRIM; both relatively selective inhibitors of neuronal NOS) were used. Mechanical/thermal nociceptive threshold valu es and hindpaw weight were recorded prior to and 3 h after administrat ion of carrageenan. NOS inhibitors (5-25 mg kg(-1), i.p.) were adminis tered 2.5 h after carrageenan. L-NAME, 7-NI and TRIM inhibited carrage enan-induced mechanical and thermal hyperalgesia. Calculated ED,, valu es (mu mol 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 p ain perception in the non-injected hindpaw or carrageenan-induced hind paw weight gain. Thus, 7-NI and TRIM, at doses previously reported not to influence cardiovascular haemodynamics, inhibit hyperalgesia in th e rat regardless of the type of noxious stimulus employed. Accordingly , selective inhibitors of neuronal NOS may prove useful for the treatm ent of prolonged pain in man. (C) 1998 Elsevier Science Ltd. All right s reserved.