Spinal effect of the cholecystokinin-B receptor antagonist CI-988 on hyperalgesia, allodynia and morphine-induced analgesia in diabetic and mononeuropathic rats

Since evidence points to the involvement of cholecystokinin (CCK) in nocice ption, we examined the effect of intrathecal CI-988, an antagonist of the C CK-B receptors, on mechanical hyperalgesia and allodynia in normal, mononeu ropathic and diabetic rats,. Owing to the anti-opioid activity of CCK, it h as been suggested that hyperactivity in the spinal CCK system is responsibl e for the low sensitivity of neuropathic pain to opioids. We therefore also evaluated the effect of the combination of i.t. CI-988 + i.v. morphine on mechanical hyperalgesia in diabetic and mononeuropathic rats using isobolog raphic analysis. Although ineffective in normal rats, CI-988 induced antino ciceptive effects in diabetic (290 +/- 20 g with a cut-off of 750 g) and mo noneuropathic (117 +/- 16 g; cut-off 750 g) rats, suggesting an involvement of the CCKergic system in neurogenic pain conditions. The combination of C I-988 and morphine showed a superadditive interaction in the diabetic rats only (477 +/- 16 g; cut-off 750 g), in comparison with the antinociceptive effect of each drug. In addition, CI-988 exhibited a weak anti-allodynic ef fect in mononeuropathic rats, and no anti-allodynic effect in diabetic rats . These results show the CCK-B receptor blockade-mediated antinociceptive e ffects and reveals the antinociceptive action of morphine in diabetic rats after CCKergic system inhibition. (C) 2000 International Association for th e Study of Pain. Published by Elsevier Science B.V. All rights reserved.