EFFECT OF TOPICAL ADMINISTRATION OF L-ARGININE ON FORMALIN-INDUCED NOCICEPTION IN THE MOUSE - A DUAL ROLE OF PERIPHERALLY FORMED NO IN PAINMODULATION

1 We investigated the effects of intraplantar (i.pl.) administration o f L-arginine and NG-nitro-L-arginine methyl eater (L-NAME) on formalin -induced behavioural nociception in the mouse. 2 L- but not D-arginine , at 0.1-1 mu g per paw, coadministered with i.pl. formalin, enhanced the second- but not the first-phase nociceptive responses, whereas it was without significant effects at 3 mu g per paw, and conversely, pro duced antinociception at 10 mu g per paw, resulting in a bell-shaped d ose-response curve. 3 L-NAME at 0.1-1 mu g per paw, when administered i.pl., exhibited antinociceptive activity in the second phase in a dos e-dependent manner, although its D-enantiomer produced no effect. 4 An antinociceptive dose (I mu g per paw) of L-NAME (i.pl.) considerably reduced the increase in second-phase nociception elicited by low doses (1 mu g per paw) of i.pl. L-arginine. The second-phase nociception de crease induced by a large dose (10 mu g per paw) of i.pl. L-arginine w as markedly reversed by i.pl. L-NAME at 0.1 mu g per paw, raising it t o a level above that of the control (formalin only). 5 These results s uggest that peripheral NO plays a dual role in nociceptive modulation, depending on the tissue level, inducing either nociceptive or antinoc iceptive responses.