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

AbstractBACKGROUND & 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.
AuthorsS V Coutinho, G F Gebhart
JournalGastroenterology (Gastroenterology) Vol. 116 Issue 6 Pg. 1399-408 (Jun 1999) ISSN: 0016-5085 [Print] United States
PMID10348823 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Enzyme Inhibitors
  • Nitric Oxide
  • Zymosan
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • NADPH Dehydrogenase
Topics
  • Abdominal Muscles (physiopathology)
  • Animals
  • Colon
  • Enzyme Inhibitors (pharmacology)
  • Hindlimb
  • Hyperalgesia (chemically induced, metabolism, physiopathology)
  • Injections
  • Injections, Spinal
  • Male
  • Muscle Contraction (physiology)
  • Muscle, Skeletal (physiopathology)
  • NADPH Dehydrogenase (metabolism)
  • Nitric Oxide (physiology)
  • Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
  • Nitric Oxide Synthase Type I
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord (metabolism)
  • Viscera (physiopathology)
  • Zymosan

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