The role of spinal cholecystokinin B receptors in thermal allodynia and hyperalgesia in diabetic mice

We examined the tail-flick response to various hear intensities in diabetic and non-diabetic mice. Heat intensities were set to one of six values by a djusting the source of voltage for a 50-W projection bulb to 20, 25, 35, 50 , 65 and 80 V. Tail-flick latencies at source voltages of 35 and 50 V in di abetic mice were significantly shorter than those in non-diabetic mice. How ever, rail-flick latencies at 25, 65 and 80 V in diabetic mice were not sig nificantly altered. Although tail-flick latencies in non-diabetic mice were not affected by i.t. pre-treatment with CI-988, a selective cholecystokini n B (CCKB) receptor antagonist, those at 35 and 50 V in diabetic mice were significantly increased. In non-diabetic mice, i.t. pre-treatment with chol ecystokinin octapeptide (CCK-8), at a dose of 0.3 ng, decreased tail-flick latencies at 35 and 50 V. Furthermore, the attenuation of tail-flick latenc ies induced by i.t. pre-treatment with CCK-8 in non-diabetic mice was rever sed by i.t. pre-treatment with CI-988. Protein kinase C (PKC) activator pho rbol-12, 13-dibutyrate (PDBu)-induced reduction in the tail-flick latencies at heat intensities of 35 and 50 V in non-diabetic mice was dose-dependent ly and significantly reversed by i.t. pre-treatment with CI-988. On the oth er hand, the CCK-g-induced thermal hyperalgesia and allodynia at heat inten sities of 35 and 50 V in non-diabetic mice were inhibited when PKC activity was inhibited by i.t. pre-treatment with calphostin C. These results indic ate that the thermal allodynia and hyperalgesia in diabetic mice may be due , at least in part, to the activation of CCKB receptors followed by the act ivation of PKC in the spinal cord. (C) 2001 Elsevier Science B.V. All right s reserved.