Cholecystokinin/opioid interactions

Cholecystokinin (CCK) acts as an anti-opioid peptide. The mechanisms of CCK -opioid interaction under normal and pathological conditions were examined with various techniques. Nerve injury induces upregulation of CCK mRNA and CCK2 receptors in sensory neurons. The involvement of CCK in spinal nocicep tion in normal and axotomized rats was examined. The CCK2 receptor antagoni st CI-988 did not reduce spinal hyperexcitability following repetitive C-fi ber stimulation in normal or axotomized rats, suggesting that CCK is probab ly not released from injured primary afferents. With in vivo microdialysis intravenous (i.v.) or intrathecal (i.t.) morphine increased the extracellul ar level of CCK in the dorsal horn in a naloxone reversible manner. Morphin e also released CCK after axotomy, but not during carrageenan-induced infla mmation. In contrast, K+-stimulation failed to increase extracellular level s of CCK in axotomized rats, but did so in inflamed rats. Double-coloured i mmunofluorescence technique revealed partial co-localization between CCK-li ke immunoreactivity (LI) and mu-opioid receptor (MOR)-LI in superficial dor sal horn neurons. The presence of MOR in CCK containing neurons suggests a possible direct influence of opioids on CCK release in the spinal cord. Axo tomy, but not inflammation, induced a moderate decrease in CCK- and MOR-LI in the dorsal horn. I.v. morphine further temporarily reduced CCK- and MOR- LIs in axotomized, but not in normal or inflamed, rats. While the effect of morphine on CCK-LI can be interpreted as the result of increased CCK relea se, the effect on MOR-LI may be related to changes in the microenvironment of the dorsal ham induced by nerve injury. (C) 1999 Elsevier Science B.V. A ll rights reserved.