The nociceptin receptor is another new type of opioid receptor found after mu-opioid receptor, kappa-opioid receptor and delta-opioid receptor, which not only has structural similar features to classical opioid receptors, but also mediates same or similar intracellular biological response. Nociceptin receptor has a unique modulation of pain response. On the one hand, it usually exerts the analgesic effect at the dorsal root ganglia and spinal cord levels, and synergistic with other opioid receptors at the level of the spinal cord to enhance the analgesic effect. On the other hand, at the level of the spinal cord, nociceptin receptor produces hyperalgesia that antagonizes the analgesic effects of other opioid receptors. In addition, the regulation of pain sensation by nociceptin receptors also shows some differences among different species. This provides a theoretical basis for further elucidation of the pain regulation of the endogenous opioid system.