The release of spinal prostaglandin E2 and the effect of nitric oxide synthetase inhibition during strychnine-induced allodynia.

Abstract

The removal of spinal glycinergic inhibition by intrathecal strychnine produces an allodynia-like state in rodents. Our objective was to measure spinal prostaglandin E2 (PGE2) release during strychnine-allodynia and examine the effects of Nomega-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthetase. Under halothane, rats were fitted with intrathecal and spinal microdialysis catheters, and microelectrodes implanted into the locus coeruleus for measurement of catechol oxidation current (CAOC) using voltammetry. Animals were then administered urethane and treated as follows: 1) baseline control 10 min, intrathecal strychnine (40 microg) 10 min, 10 min of hair deflection, and 2) 10-min control followed by intrathecal strychnine (40 microg) with hair deflection for 60 min. Spinal dialysate samples were collected for PGE2 levels determined by using immunoassay. In separate experiments, the effect of intrathecal strychnine (40 microg) followed by hair deflection was studied in rats pretreated with intrathecal l-NOARG (50 nmol). After intrathecal strychnine, hair deflection significantly increased spinal PGE2 release (619% +/- 143%), locus coeruleus CAOC (181% +/- 6%), and mean arterial pressure (123% +/- 2%) P < 0.05. Pretreatment with intrathecal l-NOARG significantly inhibited strychnine-allodynia. In this model, hair deflection evokes spinal PGE2 release, locus coeruleus activation, and an increase in mean arterial pressure. L-NOARG pretreatment attenuated the locus coeruleus CAOC, a biochemical index of strychnine-allodynia, suggesting a mediator role of nitric oxide. A mediator role of nitric oxide is also implicated, helping to explain the pathophysiology of this allodynic pain.

• Authors: B Milne, S R Hall, M E Sullivan, C Loomis
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 93 Issue 3 Pg. 728-33 (Sep 2001) ISSN: 0003-2999 [Print] United States
• PMID: 11524348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catechols
• Enzyme Inhibitors
• Poisons
• Nitroarginine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type I
• Nos1 protein, rat
• Strychnine
• Dinoprostone

Topics

• Animals
• Catechols (metabolism)
• Dinoprostone (metabolism)
• Enzyme Inhibitors (pharmacology)
• Hemodynamics (drug effects)
• Hyperalgesia (chemically induced, metabolism)
• Male
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitric Oxide Synthase Type I
• Nitroarginine (pharmacology)
• Oxidation-Reduction
• Physical Stimulation
• Poisons
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (drug effects, metabolism)
• Strychnine