8101218

pubmed:Citation

1

The present study was designed to characterize the antinociception produced by the administration of a potent muscarinic agonist into the intrathecal space of the lumbar spinal cord of male Sprague-Dawley rats. Seven days after surgical implantation of intrathecal catheters, animals were injected with graded doses of (+)-cis-methyldioxolane. (+)-cis-Methyldioxolane produced hot-plate and tail-flick antinociception for up to 90 min, peaking 5 to 30 min after injection. The dose of (+)-cis-methyldioxolane that inhibited nociception by 50% was 12 nmol in both the hot-plate and tail-flick tests. This antinociception was not accompanied by a general depression of other spontaneous motor responses. The tissue concentration of (+)-cis-methyl-dioxolane in the lumbar spinal cord present at the time of maximal hot-plate and tail-flick antinociception was approximately 12 microM. In similarity to (+)-cis-methyldioxolane, intrathecally administered (+)-muscarine also produced strong hot-plate and tail-flick antinociceptive responses. In contrast, intrathecally administered N-methylcarbachol, a nicotinic agonist, had no effect on nociception. Five-minute pretreatment with graded doses of pirenzepine, methoctramine, idazoxan, LY53857, or S-(-)-zacopride each significantly antagonized hot-plate and tail-flick antinociception produced by 37.5 nmol of (+)-cis-methyldioxolane in a dose-related manner with median effective antagonist doses in the range of 0.4 to 2.2 nmol. Intrathecal pretreatment with graded doses of prazosin or naloxone enhanced the antinociception produced by (+)-cis-methyldioxolane in the tail-flick but not the hot-plate tests. Intrathecal vehicle, S(-)-propranolol or mecamylamine did not alter (+)-cis-methyldioxolane-induced antinociception. The data suggest that the antinociceptive responses produced by intrathecally administered (+)-cis-methyldioxolane involve the stimulation of muscarinic M1 and/or M2 cholinergic receptors, and may also involve activation of alpha-2 adrenergic, 5-hydroxytryptamine1c/2 and 5-hydroxytryptamine3 serotonergic receptor systems at the level of the lumbar cord.

eng

IM

MEDLINE

0022-3565

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NLM

329-38

pubmed-meshheading:8101218-Adrenergic alpha-Antagonists, pubmed-meshheading:8101218-Analgesia, pubmed-meshheading:8101218-Animals, pubmed-meshheading:8101218-Carbachol, pubmed-meshheading:8101218-Diamines, pubmed-meshheading:8101218-Dioxolanes, pubmed-meshheading:8101218-Dose-Response Relationship, Drug, pubmed-meshheading:8101218-Drug Interactions, pubmed-meshheading:8101218-Injections, Spinal, pubmed-meshheading:8101218-Male, pubmed-meshheading:8101218-Mecamylamine, pubmed-meshheading:8101218-Muscarine, pubmed-meshheading:8101218-Nociceptors, pubmed-meshheading:8101218-Pain Measurement, pubmed-meshheading:8101218-Parasympathomimetics, pubmed-meshheading:8101218-Pirenzepine, pubmed-meshheading:8101218-Rats, pubmed-meshheading:8101218-Rats, Sprague-Dawley, pubmed-meshheading:8101218-Receptors, Adrenergic, alpha, pubmed-meshheading:8101218-Receptors, Muscarinic, pubmed-meshheading:8101218-Receptors, Opioid, pubmed-meshheading:8101218-Receptors, Serotonin, pubmed-meshheading:8101218-Spinal Cord, pubmed-meshheading:8101218-Time Factors, pubmed-meshheading:8101218-Tissue Distribution

Characterization of the antinociception produced by intrathecally administered muscarinic agonists in rats.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't