Cholecystokinin fails to block the spinal inhibitory effects of nociceptin in sham operated and neuropathic rats

Cholecystokinin (CCK) has a number of roles in the central nervous system and can reduce the analgesic effect of activation of mu (micro), delta (delta) and kappa (kappa) opioid receptors. CCK has been proposed to be a major reason for reduced effects of morphine after nerve injury. This study examines if CCK modulates the effect of the Opioid Receptor Like-1 (ORL1) agonist, nociceptin on dorsal horn neurone activity in vivo in the spinal nerve ligation model of neuropathic pain compared with sham-operated and naive rats. In naive and neuropathic rats nociceptin alone inhibited the C-fibre evoked response, post-discharge, wind-up and input, while in sham operated rats nociceptin did not cause any inhibition but by contrast caused a facilitation of post-discharge and wind-up. CCK alone had no significant effect, although did cause slight facilitation in the three groups. In the presence of CCK the inhibitory effect of nocieceptin was blocked in naive animals, but in contrast the inhibitory effect of nociceptin was enhanced by CCK in sham and neuropathic rats. These results emphasize the differences between ORL1 and other opioid receptors. This loss of the inhibitory effect of CCK on nociceptin after nerve injury may be of clinical interest in the treatment of neuropathic pain.