title: Presynaptic inhibitory effects of fluvoxamine, a selective serotonin reuptake inhibitor, on nociceptive excitatory synaptic transmission in spinal superficial dorsal horn neurons of adult mice.
abstract: 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.
authors.affiliation: Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan.
authors.forename: Orie
authors.initials: O
authors.lastname: Tomoyose
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kodama
authors.forename: Hideki
authors.initials: H
authors.lastname: Ono
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tanabe
mesh_terms: D000375:Aging; D000818:Animals; D003864:Depression, Chemical; D016666:Fluvoxamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008815:Mice, Inbred Strains; D059225:Nociception / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors