鞘内注射吗啡的不同效应及其与胆囊收缩素B拮抗剂的相互作用对大鼠两种实验性单神经病模型热痛觉过敏的影响

Differential effects of intrathecally administered morphine and its interaction with cholecystokinin-B antagonist on thermal hyperalgesia following two models of experimental mononeuropathy in the rat.

作者信息

Yamamoto T, Sakashita Y

机构信息

Department of Anesthesiology, School of Medicine, Chiba University, Japan.

出版信息

Anesthesiology. 1999 May;90(5):1382-91. doi: 10.1097/00000542-199905000-00023.

DOI:10.1097/00000542-199905000-00023

PMID:10319787

Abstract

BACKGROUND

Cholecystokinin-B receptor activation has been reported to reduce morphine analgesia. Neuropathic pain is thought to be relatively refractory to opioids. One possible mechanisms for a reduced effect of morphine on neuropathic pain is the induction of cholecystokinin in the spinal cord by nerve injury. The authors evaluated the role of the spinal cholecystokinin-B receptor on morphine analgesia in two rat neuropathic pain models: chronic constriction injury and partial sciatic nerve injury.

METHODS

A chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. A partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 7 and 11 days after the nerve injury. The effect of the drugs was reflected in the degree of paw withdrawal latency to thermal nociceptive stimulation. The paw withdrawal latencies of injured and uninjured paws were measured 5, 15, 30, and 60 min after the drugs were injected.

RESULTS

In the chronic constriction injury model, intrathecal morphine increased the paw withdrawal latencies of injured and uninjured paws. PD135158, a cholecystokinin-B receptor antagonist, potentiated the analgesic effect of morphine on injured and uninjured paws. In the partial sciatic nerve injury model, the effect of morphine on the injured paw was less potent than that on the uninjured paw, and PD135158 potentiated the morphine analgesia in the uninjured paw and had only a minor effect on the morphine analgesia in the injured paw.

CONCLUSIONS

The effectiveness of morphine for thermal hyperalgesia after nerve injury depends on the type of nerve injury. The role of the cholecystokinin-B receptor in morphine analgesia in thermal hyperalgesia after nerve injury also depends on the type of nerve injury.

摘要

背景

据报道，胆囊收缩素B受体激活可降低吗啡镇痛效果。神经病理性疼痛被认为对阿片类药物相对不敏感。吗啡对神经病理性疼痛作用减弱的一种可能机制是神经损伤诱导脊髓中胆囊收缩素的产生。作者在两种大鼠神经病理性疼痛模型（慢性压迫损伤和部分坐骨神经损伤）中评估了脊髓胆囊收缩素B受体在吗啡镇痛中的作用。

方法

通过在右侧坐骨神经周围放置四个宽松结扎的线结造成慢性压迫损伤。通过紧密结扎右侧坐骨神经的三分之一至二分之一造成部分坐骨神经损伤。所有药物均在神经损伤后第7天和第11天鞘内注射。药物的作用通过对热伤害性刺激的爪退缩潜伏期程度来反映。在注射药物后5、15、30和60分钟测量受伤爪和未受伤爪的爪退缩潜伏期。