Pain
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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.
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The effects of nitrous oxide (N2O) are thought to be mediated by several pharmacological pathways at different levels of the central nervous system. Here, we focus on excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord with respect to its importance for the nociceptive processing. The effects of 50% N2O on electrically evoked and spontaneous excitatory glutamatergic transmission and on the response to exogenous administration of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptor agonists were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. ⋯ Moreover N2O changed the distribution of miniature EPSC amplitude, but not frequency distribution in most neurons. N2O inhibits glutamatergic transmission in the superficial dorsal horn by modulating the NMDA- and AMPA-receptors. Our findings raise the possibility that the antinociceptive effect of N2O may be directly mediated at the level of the spinal cord.