Activation of spinal nociceptin receptors induces cardiovascular depression and antinociception in an independent manner in mice

The nociceptin receptor (NOP) was discovered in 1994 and was designated opioid-like receptor; activation of NOP leads to reduced neuronal excitability. Although suggested by the anatomical localization of NOP in brain or spinal cord, the cardiovascular or nociceptive effects of its endogenous ligand, nociceptin, are equivocal. Taking advantage from intrathecal application of nociceptin to simultaneously activate NOP on sympathetic preganglionic neurons in the intermediolateral column (IML) and superficial laminae of dorsal horn, we investigated whether the nociceptin-induced cardiovascular effects engage the participation of baroreflex, and whether the concurrently elicited changes in blood pressure and pain responses are interrelated. NOPs in the thoracic spinal cord of ICR or C57BL/6 mice were identified with immunofluorescence staining and were activated through intrathecal administration of nocicetpin. The elicited changes in cardiovascular parameters and tail-flick nociceptive responses were measured. Positive immunoreactivity against NOP colocalized with neurons in the IML and superficial dorsal horn layers of thoracic spinal cord. Intrathecal administration of nociceptin (1, 2, or 5 nmol) elicited a significant and dose-dependent decrease in blood pressure or heart rate that was paralleled by reduced baroreflex-mediated sympathetic vasomotor tone and mirrored by augmented cardiac vagal baroreflex, alongside prolonged tail-flick latency with an efficacy of hypotension