Opioid self-administration in the nerve-injured rat
Opioid self-administration in the nerve-injured rat
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DOI：
10.1097/00000542-200702000-00020
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发表时间：
2007-02-01
期刊：
影响因子：
8.8
通讯作者：
Eisenach, James C.
中科院分区：
文献类型：
--
作者：
Martin, Thomas J.;Kim, Susy A.;Eisenach, James C.
背景：神经性疼痛与几种感觉异常有关，包括异常性疼痛和自发性疼痛。神经性疼痛患者服用阿片类药物的动机是减轻疼痛和异常性疼痛。然而，实验动物研究几乎完全依赖于异常性疼痛的反射性戒断措施。作者检查了阿片类药物自我调节摄入的药理学；在有或没有神经损伤的大鼠中，比较药物摄入与异常性疼痛逆转的比率。方法：大鼠静脉留置导尿管，结扎L5、L6脊髓神经。然后训练大鼠自我使用常用的阿片类药物（海洛因）和常用的阿片类药物（吗啡、芬太尼、氢吗啡酮和美沙酮）。此外，自我给药的大鼠在自我给药之前被给予可乐定或腺苷，以评估阿片类药物的节省效果。结果：神经损伤显著降低了低剂量阿片类药物的强化作用，只有降低机械超敏反应的每种阿片类药物剂量才能维持脊髓神经结扎后的自我给药。药物消耗率与每次阿片类药物的抗异动作用持续时间相关。脊髓神经结扎大鼠鞘内注射可乐定或腺苷逆转机械性超敏反应，但只有可乐定减少海洛因自我给药。结论：阿片类药物的自我给药会因神经损伤而发生明显改变，药物摄入率与异常性疼痛的逆转有关。鞘内可乐定，而不是腺苷，在自我给药的大鼠中产生阿片节约作用。因此，调节大鼠阿片类药物消耗的神经生物学机制似乎在神经损伤后发生了改变。
Background: Neuropathic pain is associated with several sensory abnormalities, including allodynia as well as spontaneous pain. Opioid intake in neuropathic pain patients is motivated by alleviation of both pain and allodynia. However, laboratory animal studies rely almost exclusively on reflexive withdrawal measures of allodynia. The authors examined the pharmacology of self-regulated intake of opioids; in rats with or without nerve injury and compared the rate of drug intake to reversal of allodynia.Methods: Rats were implanted with intravenous catheters, and the L5 and L6 spinal nerves were ligated in half of these animals. Rats were then trained to self-administer a commonly abused opioid (heroin) and commonly prescribed opioids (morphine, fentanyl, hydromorphone, and methadone). in addition, rats trained to self-administer heroin were given either clonidine or adenosine spinally before self-administration sessions to assess opioid-sparing effects.Results: Nerve injury significantly decreased the reinforcing effects of low doses of opioids, and only doses of each opioid that reduced mechanical hypersensitivity maintained self-administration after spinal nerve ligation. The rate of drug consumption was correlated with the duration of the antiallodynic effect for each dose of opioid. Intrathecal administration of clonidine or adenosine reversed mechanical hypersensitivity, but only clonidine reduced heroin self-administration in rats with spinal nerve ligation.Conclusion: Opioid self-administration is significantly altered by nerve injury, with rate of drug intake being correlated with reversal of allodynia. Intrathecal clonidine, but not adenosine, produces opioid-sparing effects in self-administering rats. The neurobiologic mechanisms that regulate opioid consumption in rats therefore seem to be altered after nerve injury.