A role for spinal nitric oxide in mediating visceral hyperalgesia in the rat.
OBJECTIVE
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.
Coutinho
S V
SV
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Gebhart
G F
GF
D000009:Abdominal Muscles / Q000503:physiopathology; D000818:Animals; D003106:Colon; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006614:Hindlimb; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007267:Injections; D007278:Injections, Spinal; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D014781:Viscera / Q000503:physiopathology*; D015054:Zymosan
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D015054:Zymosan; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D009252:NADPH Dehydrogenase