Journal of Pharmacological Sciences | |
Presynaptic Inhibitory Effects of Fluvoxamine, a Selective Serotonin Reuptake Inhibitor, on Nociceptive Excitatory Synaptic Transmission in Spinal Superficial Dorsal Horn Neurons of Adult Mice | |
Hideki Ono1  Mitsuo Tanabe3  Daisuke Kodama2  Orie Tomoyose1  | |
[1] Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan;Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Japan;Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Japan | |
关键词: fluvoxamine; patch clamp; excitatory postsynaptic current; strontium; spinal cord; | |
DOI : 10.1254/jphs.14127FP | |
学科分类:药学 | |
来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society | |
【 摘 要 】
References(40)Fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, has been shown to exert analgesic effects in humans and laboratory animals. However, its effects on spinal nociceptive synaptic transmission have not been fully characterized. Here, whole-cell recordings were made from dorsal horn neurons in spinal slices with attached dorsal roots from adult mice, and the effects of fluvoxamine on monosynaptic A-fiber- and C-fiber-mediated excitatory postsynaptic currents (EPSCs) evoked in response to electrical stimulation of a dorsal root were studied. Fluvoxamine (10 �? 100 μM) concentration-dependently suppressed both monosynaptic A-fiber- and C-fiber-mediated EPSCs, which were attenuated by the selective 5-HT1A receptor antagonist WAY100635. In the presence of the selective 5-HT3 receptor antagonist tropisetron, fluvoxamine hardly suppressed A-fiber-mediated EPSCs, whereas its inhibitory effect on C-fiber-mediated EPSCs was not affected. Although fluvoxamine increased the paired-pulse ratio of A-fiber-mediated EPSCs, it increased the frequency of spontaneous and miniature EPSCs (sEPSCs and mEPSCs). Since sEPSCs and mEPSCs appeared to arise largely from spinal interneurons, we then recorded strontium-evoked asynchronous events occurring after A-fiber stimulation, whose frequency was reduced by fluvoxamine. These results suggest that fluvoxamine reduces excitatory synaptic transmission from primary afferent fibers via presynaptic mechanisms involving 5-HT1A and/or 5-HT3 receptors, which may contribute to its analgesic effects.
【 授权许可】
Unknown
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