Orphanin FQ nociceptin modulates glutamate- and kainic acid-induced currents in acutely isolated rat spinal dorsal horn neurons

The heptadecapeptide orphanin FQ (OFQ), also known as nociceptin (NOC), is a newly discovered endogenous ligand for the opioid-like G-protein coupled receptor, ORL1. In the present study, the effects of OFQ/NOC on glutamate (Glu), kainic acid (KA) and quisqualic acid (QA) induced currents were examined in isolated rat spinal dorsal horn neurons of young rats using whole-cell patch-clamp techniques. Glu, KA and QA elicited rapid inward currents in 90%, 69%, 83% of tested neurons. OFQ/NOC(0.03 similar to 300 nM) failed to induce any changes of membrane currents, but modulated Glu-, KA- and QA-elicited currents. OFQ/NOC inhibited and potentiated Glu-induced currents in 40.6% and 27.3% of examined cells (n=106) respectively. In about one third examined neurons, OFQ/NOC had no detectable effects on Glu responses. OFQ/NOC also inhibited and enhanced KA- and QA-induced currents (inhibition: KA, 67.1%, n=76; QA, 50%, n=36. Potentiation: KA, 23.7%, n=76; QA, 16.7%, n=36). In about 10% of tested cells, Glu-induced currents were potentiated after the application of OFQ/NOC, and lasted for 20 similar to 30 min. The inhibitory effects of OFQ/NOC on KA and QA responses were naloxone-insensitive. The C-terminal fragment OFQ(8-17) presented same effects on EAA-induced responses. Taken together, OFQ/NOC primarily inhibited Glu-, KA- and QA-induced currents in isolated rat spinal dorsal horn neurons via non-opioid mechanism, which might contribute to nociceptive transmission in the spinal level.