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

In order to further investigate the interaction between the octapeptide cho lecystokinin and opioid analgesia in the spinal cord we used double-colour immunofluorescence to examine the anatomical distribution of cholecystokini n and mu-opioid receptors in the dorsal horn, as well as the effect of morp hine on cholecystokinin- and mu-opioid receptor-like immunoreactivities fol lowing peripheral nerve injury and inflammation. mu-opioid receptor-like im munoreactivity was present in 65.6% of cholecystokinin-positive neurons in laminae I and II of rat spinal cord. Conversely, 40.4% of mu-opioid recepto r-positive neurons contained cholecystokinin-like immunoreactivity. Systemi c application of morphine (1, 3 or 10 mg/kg; i.v.) after sciatic nerve sect ion significantly, but reversibly, decreased mu-Opioid receptor-like immuno reactivity in the medial half of lamina II in segment L5 of the ipsilateral dorsal horn, and cholecystokinin-like immunoreactivity was also markedly r educed in the same region. These effects were dose- and time-dependent and could be prevented by naloxone preadministration. In contrast, no significa nt change in the pattern of distribution or intensity of mu-opioid receptor - and cholecystokinin-like immunoreactivities was observed in intact rats o r during peripheral inflammation. These results provide a cellular basis for the interaction of mu-opioid rec eptors and cholecystokinin at the spinal level by showing a high degree of co-existence of these two molecules in local interneurons, and also show th at morphine can induce rapid and short lasting effects on mu-opioid recepto rs after peripheral nerve injury. The results contribute to our understandi ng of how endogenous cholecystokinin reduces the analgesic effect of morphi ne. (C) 1999 IBRO. Published by Elsevier Science Ltd.