Effects of nociceptin/orphanin FQ on excitatory synaptic transmission in rat trigeminal caudal neurons

ABSTRACT

spinal trigeminal nucleus(medullary dorsal hornMDH) is implicated in the processing of nociceptive information in the orofacial region. In the present study, whole cell patch clamp recordings were carried out on MDH neurons in brainstem slice of neonatal rats to investigate the characteristics of spontaneous excitatory postsynaptic currents(sEPSCs) and the roles of nociceptin/orphanin FQ on excitatory synaptic transmission. In the presence of strychnine(1 microM) and bicuculline(20 microM), spontaneous inward currents at -70mV were observed. The baseline frequency, amplitude and decay time constant of sEPSCs were 2.0+/-0.5Hz, 23.0+/-1.8pA, 3.8+/-0.2ms, respectively. sEPSCs were mediated by non-NMDA and NMDA receptors. The specific AMPA receptor antagonist GYKI-52466(50 microM) completely blocked the non-NMDA mediated sEPSCs, indicating that they are mediated by an AMPA-preferring receptor. Perfusion of the opioid orphan receptor(ORL1) agonist nociceptin(3 microM) reduced the freque ncy of sEPSCs and miniature EPSCs(mEPSCs). The effects of nociceptin were blocked by the selective ORL1 receptor antagonist (Nphe')nociceptin(1-13)NH2(3 microM) and were not affected by the non-specific opioid receptor antagonist naloxone(10 microM). To investigate the specificity of this synaptic inhibition, we selectively activated the nociceptive C fibers with capsaicin, which induced a strong increase in the frequency of sEPSCs. In the presence of nociceptin, the response to capsaicin was diminished. In conclusion, these results suggest that nociceptin inhibits excitatory synaptic transmission in the MDH by acting on presynaptic ORL1 receptors.