A role for spinal nitric oxide in mediating visceral hyperalgesia in the rat

Background & Aims: Intracolonic instillation of zymosan in rats produces hyperalgesia (i.e., facilitates the visceromotor response to colorectal distention) mediated by activity at spinal N-methyl-D-aspartate (NMDA) and non-NMDA receptors, Nitric oxide (NO.) production often increases after NMDA receptor activation; NO. may then function as a further messenger. This study was designed to investigate the role of spinal NO. in this model of visceral hyperalgesia. Methods: Zymosan or saline was given intracolonically, and the visceromotor response to noxious colorectal distention (80 mm Hg, 20 seconds) was measured 3 hours afterward. Results: There was a significant enhancement of the visceromotor response in zymosan-, but not saline-treated, rats. This hyperalgesia was dose-dependently and reversibly attenuated by intrathecal administration of the nonselective NO. synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (100-800 nmol) as well as by the selective neuronal NOS inhibitor ARL 17477 (30-600 nmol). In support of these observations, there was a significant increase in the number of cells labeled for NADPH diaphorase or neuronal NOS in the lumbosacral spinal cord after intracolonic instillation of zymosan, but not saline. Conclusions: These data suggest that colonic inflammation induces the expression of neuronal NOS in the spinal cord and that increased production of spinal NO. is necessary for maintenance of zymosan-produced visceral hyperalgesia.