Role of nitric oxide in zymosan induced paw inflammation and thermal hyperalgesia

Objective: To assess the involvement of spinal inducible nitric oxide synth ase (iNOS) in inflammation and nociception. Materials and Methods: The time course of iNOS mRNA expression in rat spina l cord and inflamed paw was assessed by means of quantitative real time RT- PCR. In addition, the effects of the iNOS inhibitor L-NIL on inflammatory p aw edema and thermal hyperalgesia were studied in comparison to those of th e NO-donor RE-2047. L-NIL (3, 9, 27 and 81 mg/kg) and RE-2047 (3, 9 and 27 mg/kg) or vehicle were administered orally 15 min prior to the intraplantar injection of 0.625 mg zymosan. Results: Following zymosan injection, mRNA expression of iNOS increased in the inflamed paw and spinal cord with a maximum at 2.5 and 4 h, respectivel y. In the spinal cord iNOS mRNA started to decline at 10h whereas it remain ed at maximum in the inflamed paw up to the end of the observation period o f 24 h. As expected, RE-2047 had significant pronociceptive and proinflamma tory effects. L-NIL significantly reduced paw inflammation at 27 and 81 mg/ kg but failed to reduce hyperalgesia at the doses tested. Conclusions: The results show that iNOS is upregulated in the inflamed tiss ue and spinal cord with a similar time course. The effects obtained with L- NIL suggest that iNOS differently contributes to the inflammatory and nocic eptive response induced by zymosan.