Presynaptic inhibitory effects of fluvoxamine,a selective serotonin reuptake inhibitor,on nociceptive excitatory synaptic transmission in spinal superficial dorsal horn neurons of adult mice

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. © the japanese pharmacological society.