Rlc. Handy et Pk. Moore, EFFECTS OF SELECTIVE INHIBITORS OF NEURONAL NITRIC-OXIDE SYNTHASE ON CARRAGEENAN-INDUCED MECHANICAL AND THERMAL HYPERALGESIA, Neuropharmacology, 37(1), 1998, pp. 37-43
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.