title: Effect of morphine on cholecystokinin and mu-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 mu-opioid receptors in the dorsal horn, as well as the effect of morphine on cholecystokinin- and mu-opioid receptor-like immunoreactivities following peripheral nerve injury and inflammation. Mu-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 mu-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 mu-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 mu-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 mu-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 mu-opioid receptors after peripheral nerve injury. The results contribute to our understanding of how endogenous cholecystokinin reduces the analgesic effect of morphine.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: de Araujo Lucas
authors.forename: R
authors.initials: R
authors.lastname: Elde
authors.forename: Z
authors.initials: Z
authors.lastname: Wiesenfeld-Hallin
authors.forename: T
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D019771:Axotomy; D002766:Cholecystokinin / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; D002766:Cholecystokinin