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摘要：
目的：研究纳洛酮对神经病理性疼痛的抗伤害效应及其对脊髓后角阿片受体表达的影响。方法：雄性SD大鼠，体重200g～250g，建立CCI神经病理性疼痛动物模型，依不同治疗用药分为4组,纳洛酮治疗组24只，其余各组每组8只：假手术+生理盐水治疗组（Sham+Saline Group,Sham-S）;CCI+生理盐水治疗组（CCI+ Saline Group,CCI-S）;CCI+纳洛酮治疗组（CCI+ Naloxone Group,CCI-N）;CCI+吗啡治疗组（CCI+ Morphine Group,CCI-M）。术前用von Frey测试缩爪阈值（paw withdrawal threshold ，PWT）。术后第7天开始给予治疗，至术后第14天，共计8天。每天皮下注射生理盐水1mL ，纳洛酮10mg•kg−1（容量1 mL），吗啡10 mg•kg−1（容量1 mL）。于术后第1、3、5天及7、9、11、13、14天注射药物或生理盐水前后用von Frey测定PWT值。纳洛酮治疗组于7、9、11、14天注射药物之后12h各取4只大鼠处死，取L3–L5脊髓后角组织Western blot检测阿片受体表达。结果：CCI成功诱导了大鼠同侧后爪痛觉过敏。CCI术后7d开始给予不同治疗，生理盐水治疗没有改变CCI大鼠同侧的机械痛敏阈值，而纳洛酮与吗啡治疗均产生了明显的抗伤害效应，治疗的时间-效应曲线下面积（AUC），CCI-N组、CCI-M组与CCI-S组比较显著降低，差异有统计学意义，CCI-N组与CCI-M组比较无统计学差异。Western blot检测结果显示，术后11d、14d脊髓后角δ阿片受体(DOR)表达较术后7d明显增高。而纳洛酮对CCI大鼠脊髓后角μ(MOR)、κ(KOR)受体表达无影响，β-actin（50kDa）表达无统计学差异。结论：纳洛酮作为阿片受体拮抗剂对CCI神经病理性疼痛具有一定的抗伤害效应，其机制之一可能是通过影响脊髓后角阿片受体的表达而发挥作用。
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Abstract: Objectives: To investigave the effects of naloxone on neuropathic pain induced by chronic constriction injury (CCI) and expression of opioid receptors in spinal dorsal horn. Methods: Take male SD rats with the weight of 200g～250g as the research objects, to establish an animal model of neuropathic pain by chronic constriction injury(CCI) and divided into 4 groups according to different treatment, that is Sham+Saline Group (Sham-S), CCI+ Saline Group (CCI-S), CCI+ Naloxone Group (CCI-N) and CCI+ Morphine Group (CCI-M), 24 rats in treatment groups of naloxone, 8 rats in other groups. Before the operation, von Frey was used to test paw withdrawal threshold (PWT).Treatment started from 7th days to 14th days, 8 days altogether, which is injecting 1ml normal saline, 10mg.kg−1 naloxone, and 10mg.kg−1 morphine every day. Then von Frey was used to test paw withdrawal threshold (PWT) on different time after the injection. The naloxone treatment group took 4 rats after 12 hours’ injection on 7th, 9th, 11th and 14th day and tested the expression opioid receptors in spinal dorsal horn of L3-L5 by Western blot. Results: CCI induced ipsilateral hindpaw hyperalgesia successfully. Different treatments started after 7days of CCI operation, normal saline didn’t change mechanical allodynia threshold in CCI rats, while naloxone and morphine treatment has produced a significant antinociceptive effect. The area under curve (AUC), CCI-N group and CCI-M group have reduced dramatically compared with CCI-S group, which has obvious statistical significance, and there is no statistical significance between CCI-N group and CCI-M group. The results of Western blot test shows that the expression of theδopioid receptors (DOR) in spinal dorsal horn on the 11th day and 14th day has obvious increased than on the 7th day. While there is no change expression of μ opioid receptors (MOR)and κ opioid receptors (KOR) in spinal dorsal horn. Conclusion: Naloxone, as an opioid receptor antagonist, has antinociceptive effect on CCI neuropathic pain, one of which mechanisms is by affecting the expression of opioid receptors in spinal dorsal horn.
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