Pain
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We assessed whether intrathecal administration of the uncompetitive and competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could produce differential modulation on chemical and mechanical nociception in normal and monoarthritic rats. In addition, the antinociceptive interaction of ketamine and (+/-)CPP on monoarthritic pain was also studied using isobolographic analysis. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. ⋯ Irrespective of the nociceptive test employed, both antagonists showed greater antinociceptive activity in monoarthritic than in healthy rats. Combinations produced synergy of a supra-additive nature in the capsaicin test, but only additive antinociception in paw pressure testing. The efficacy of the drugs, alone or combined, is likely to depend on the differential sensitivity of tonic versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.
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Comparative Study
Serotonin (5-HT) excites rat masticatory muscle afferent fibers through activation of peripheral 5-HT3 receptors.
In the present study, we combined immunohistochemical experiments with in vivo single unit recordings to examine whether 5-HT(3) receptors are expressed by masticatory (masseter and temporalis) sensory ganglion neurons and to investigate the effects of intramuscular injection of 5-HT on the excitability and mechanical threshold of rat masticatory muscle afferent fibers. The expression of 5-HT(3) receptors by masticatory ganglion neurons was examined using immunohistochemical techniques. In vivo extracellular single unit recording techniques were used to assess changes in the excitability of individual masticatory muscle afferent fibers. ⋯ Unexpectedly, a significant concentration-related decrease in median blood pressure in response to 5-HT injection was found. This 5-HT-induced decrease in blood pressure was not antagonized by tropisetron or mimicked by 2-methyl-5-HT, indicating that the drop in blood pressure was not 5-HT(3) receptor-mediated. The present results indicate that 5-HT excites slowly conducting masticatory muscle afferent fibers through activation of peripheral 5-HT(3) receptors, and suggest that similar mechanisms may contribute to 5-HT-evoked muscle pain in human subjects.