5-HT_1B receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons

BACKGROUND AND PURPOSE Although 5-HT_1B receptors are expressed in trigeminal sensory neurons, it is still not known whether these receptors can modulate nociceptive transmission from primary afferents onto medullary dorsal horn neurons. EXPERIMENTAL APPROACH Primary afferent-evoked EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices using a conventional whole-cell patch clamp technique under a voltage-clamp condition. KEY RESULTS CP93129, a selective 5-HT_1B receptor agonist, reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, CP93129 reduced the frequency of spontaneous miniature EPSCs without affecting the current amplitude. The CP93129-induced inhibition of EPSCs was significantly occluded by GR55562, a 5-HT_1B/1D receptor antagonist, but not LY310762, a 5-HT_1D receptor antagonist. Sumatriptan, an anti-migraine drug, also decreased EPSC amplitude, and this effect was partially blocked by either GR55562 or LY310762. On the other hand, primary afferent-evoked EPSCs were mediated by the Ca ²⁺ influx passing through both presynaptic N-type and P/Q-type Ca²⁺ channels. The CP93129-induced inhibition of EPSCs was significantly occluded by ω-conotoxin GVIA, an N-type Ca²⁺ channel blocker. CONCLUSIONS AND IMPLICATIONS The present results suggest that the activation of presynaptic 5-HT_1B receptors reduces glutamate release from primary afferent terminals onto medullary dorsal horn neurons, and that 5-HT_1B receptors could be, at the very least, a potential target for the treatment of pain from orofacial tissues.