Coudoré-Civiale M A, Courteix C, Boucher M, Méen M, Fialip J, Eschalier A, Ardid D
INSERM EPI 9904, Laboratoire de Physiologie, Faculté de Pharmacie, place Henri-Dunant, 63001 Cedex 1, Clermont-Ferrand, France.
Neurosci Lett. 2000 May 26;286(1):37-40. doi: 10.1016/s0304-3940(00)01080-6.
The aim of this study was to determine the influence of an intrathecally injected cholecystokinin-B (CCK-B) receptor antagonist, CI-988, on the analgesic effect of morphine and clomipramine in diabetic rats. Administered alone, morphine (0.1 mg/kg, i.v.) and clomipramine (3 mg/kg, i.v.) have respectively no effect and only a slight effect on vocalization thresholds to paw pressure in diabetic rats, but, when coadministered with CI-988 (0.1 microg/rat, i.t.), an appreciable antinociceptive effect was observed. This suggests that a spinal blockade of cholecystokininergic system increases the analgesia induced by morphine or clomipramine. A CCK-B receptor antagonist could thus be used to lower dosages of morphine or antidepressant drugs in the management of neuropathic pain in humans, and thereby reduce their side effects.
本研究的目的是确定鞘内注射胆囊收缩素B（CCK - B）受体拮抗剂CI - 988对糖尿病大鼠吗啡和氯米帕明镇痛作用的影响。单独给药时，吗啡（0.1毫克/千克，静脉注射）和氯米帕明（3毫克/千克，静脉注射）对糖尿病大鼠爪部压力发声阈值分别无作用和仅有轻微作用，但是，当与CI - 988（0.1微克/只，鞘内注射）合用时，观察到明显的抗伤害感受作用。这表明胆囊收缩素能系统的脊髓阻断增强了吗啡或氯米帕明诱导的镇痛作用。因此，CCK - B受体拮抗剂可用于降低人类神经性疼痛治疗中吗啡或抗抑郁药物的剂量，从而减少其副作用。
