The analgesic efficacy of opioids is reduced in neuropathic pain states and increased in inflammation. Since the neuropeptide cholecystokinin (CCK) plays a role in the modulation of opiate-induced analgesia, the morphine-mediated release of CCK in the spinal cord of rats was compared with in vivo microdialysis in normals and different pain models. The effect of systemic and intrathecal (i.t.) morphine on the extracellular level of CCK was analyzed in the spinal cord dorsal horn of halothane-anaesthetized normal rats as well as during peripheral neuropathy and inflammation. No difference was found in basal CCK level among groups. However, morphine significantly increased extracellular CCK concentration after both systemic and spinal application in intact as well as axotomized rats and this effect was naloxone-reversible in non-lesioned animals. Similar results were seen in axotomized rats. In contrast, morphine did not induce CCK release during carrageenan-induced inflammation. These data provide evidence that the ability of opiates to release CCK under different pain states may play a key role in their analgesic efficacy.
de Araujo Lucas, G., Alster, P., Brodin, E., & Wiesenfeld-Hallin, Z. (1998). Differential release of cholecystokinin by morphine in rat spinal cord. Neurosci Lett, 245(1), 13–16.