Effect of morphine on cholecystokinin and μ-opioid receptor-like immunoreactivities in rat spinal dorsal horn neurons after peripheral axotomy and inflammation

Abstract

In order to further investigate the interaction between the octapeptide cholecystokinin and opioid analgesia in the spinal cord we used double-colour immunofluorescence to examine the anatomical distribution of cholecystokinin and μ-opioid receptors in the dorsal horn, as well as the effect of morphine on cholecystokinin- and μ-opioid receptor-like immunoreactivities following peripheral nerve injury and inflammation. μ-opioid receptor-like immunoreactivity was present in 65.6% of cholecystokinin-positive neurons in laminae I and II of rat spinal cord. Conversely, 40.4% of μ-opioid receptor-positive neurons contained cholecystokinin-like immunoreactivity. Systemic application of morphine (1, 3 or 10 mg/kg; i.v.) after sciatic nerve section significantly, but reversibly, decreased μ-Opioid receptor-like immunoreactivity in the medial half of lamina II in segment L5 of the ipsilateral dorsal horn, and cholecystokinin-like immunoreactivity was also markedly reduced in the same region. These effects were dose- and time-dependent and could be prevented by naloxone preadministration. In contrast, no significant change in the pattern of distribution or intensity of μ-opioid receptor- and cholecystokinin-like immunoreactivities was observed in intact rats or during peripheral inflammation. These results provide a cellular basis for the interaction of μ-opioid receptors and cholecystokinin at the spinal level by showing a high degree of co-existence of these two molecules in local interneurons, and also show that morphine can induce rapid and short lasting effects on μ-opioid receptors after peripheral nerve injury. The results contribute to our understanding of how endogenous cholecystokinin reduces the analgesic effect of morphine.