Electrophysiological evidence for a role of nitric oxide in prolonged chemical nociception in the rat.
The role of nitric oxide in the periphery and the spinal cord, during acute electrically-evoked and prolonged chemically-evoked nociceptive stimulation, was investigated in rats anaesthetised with halothane. The responses of single dorsal horn neurones to electrically-evoked A beta fibre and C fibre inputs were reduced by topical application (directly onto the spinal cord) of both the nitric oxide inhibitor, nitro-L-arginine methyl ester (L-NAME; 500-1500 micrograms) and the precursor of nitric oxide, L-arginine (4500 micrograms). Administration of L-NAME, either directly into the receptive field (500-1500 micrograms) or intravenously (10-100 mg/kg) had little or no effect on the acute electrically-evoked activity. Intravenous injection of L-NAME, administered 40 min prior to injection of formalin, significantly reduced the prolonged second peak of firing, with only a small effect on the short-duration first peak. Administration of L-NAME, directly into the site of injection of formalin, as a 10 min pretreatment, significantly reduced the second but not the first peak of the response. Topical application of L-NAME onto the spinal cord, as a 30 min pretreatment, significantly reduced both the first and second peaks of the response. This inhibition was not reversed by the coadministration of L-arginine, which was inhibitory by itself. Thus, nitric oxide may be involved, in a complex way, in nociceptive events both in the periphery and within the spinal cord.
Haley
J E
JE
Department of Pharmacology, University College London, U.K.
Dickenson
A H
AH
Schachter
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009412:Nerve Fibers / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester