Journal of neurophysiology
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Behavioral evidence in rats indicates that injection of tumor necrosis factor alpha (TNFalpha) into skeletal muscle results in a prolonged mechanical sensitization without gross inflammation. To investigate whether a peripheral mechanism could underlie this effect, in the present study, TNFalpha (1 or 0.1 microg) was injected into the rat masseter muscle to assess its effect on the excitability and mechanical threshold (MT) of muscle nociceptors as well as on inflammation. Expression of TNFR1 (P55 receptors) and TNFR2 (P75 receptors) by the masseter muscle and trigeminal ganglion neurons that innervate that muscle was determined by Western blot and immunohistochemistry, respectively. ⋯ P55 and P75 receptors were expressed by 29 and 62% of masseter nociceptors, respectively. These findings indicate that TNFalpha induces mechanical sensitization of masseter nociceptors that is mediated through activation of peripheral P55 and P75 receptors. These results support the hypothesis that a peripheral receptor mechanism could contribute to TNFalpha-induced noninflammatory mechanical sensitization of skeletal muscle previously reported in behaving rats.
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Analgesic effects of serotonin (5-hydroxytryptamine [5-HT]) type 3 (5-HT3) receptors may involve the release of gamma-aminobutyric acid (GABA) in the spinal dorsal horn. However, the precise synaptic mechanisms for 5-HT3 receptor-mediated spinal analgesia are not clear. In this study, we investigated whether GABAergic neurons in the superficial dorsal horn (SDH) express functional 5-HT3 receptors and how these 5-HT3 receptors affect GABAergic inhibitory synaptic transmission in the SDH, by using slice preparations from adult glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mice. ⋯ The amplitude of mIPSCs was not affected by 2-Me-5-HT, suggesting that 5-HT augments GABAergic synaptic transmission via presynaptic mechanisms. The present observations indicate that 5-HT3 receptors are expressed on both somadendritic regions and presynaptic terminals of GABAergic neurons and regulate GABAA receptor-mediated inhibitory synaptic transmission in the SDH. Taken together, these results provide clues for the underlying mechanisms of the antinociceptive actions of 5-HT3 receptors in the spinal dorsal horn.