Arthritis-induced increase in cholecystokinin release in the rat anterior cingulate cortex is reversed by diclofenac

Given a hypothesised role for CCK in the anterior cingulate cortex (ACC) for the sensation of pain, the aim of the present study was to investigate whether the increased CCK release could be affected by two different analgesic drugs, morphine and the non-selective cyclooxygenase inhibitor diclofenac. Since opioids stimulate CCK release in other CNS regions we have also studied the effect of morphine by itself on the CCK-LI release in the ACC of non-arthritic rats. Three to seven hours after intraarticular carrageenan injection, at the time when the animals are known to show pain-related behaviour, in vivo microdialysis in awake rats revealed increased CCK-LI release in the ACC. The CCK-LI release was significantly attenuated by diclofenac (25 mg/kg i.m.), but not by morphine (10 mg/kg s.c.). Neither diclofenac (25 mg/kg i.m.) nor morphine (5 or 10 mg/kg s.c.) affected the CCK-LI release in the ACC in non-arthritic rats. The results obtained with diclofenac indicate that prostaglandins contribute to the increased CCK-LI release in the ACC during monoarthritis. However, the lack of effect of morphine suggests that the CCK release in the ACC is not directly related to the sensation of pain. Further on, the failure of morphine to affect the extracellular level of CCK-LI in the ACC in control animals as well as in animals with carrageenan-induced monoarthritis is in contrast to previous studies on the frontal cortex or the dorsal horn of the spinal cord, in which similar doses of morphine stimulate CCK release. Thus, compared to these regions, CCK release may be differently regulated in the ACC.