Yamamoto T, Sakashita Y
Department of Anesthesiology, School of Medicine, Chiba University, Japan.
Anesthesiology. 1999 May;90(5):1382-91. doi: 10.1097/00000542-199905000-00023.
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.
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.
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.
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.
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。
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。
在慢性压迫损伤模型中，鞘内注射吗啡增加了受伤爪和未受伤爪的爪退缩潜伏期。胆囊收缩素B受体拮抗剂PD135158增强了吗啡对受伤爪和未受伤爪的镇痛作用。在部分坐骨神经损伤模型中，吗啡对受伤爪的作用比对未受伤爪的作用弱，PD135158增强了吗啡对未受伤爪的镇痛作用，而对受伤爪的吗啡镇痛作用影响较小。
吗啡对神经损伤后热痛觉过敏的有效性取决于神经损伤的类型。胆囊收缩素B受体在神经损伤后热痛觉过敏的吗啡镇痛中的作用也取决于神经损伤的类型。
