Cahill Catherine M, Xue Lihua, Grenier Patrick, Magnussen Claire, Lecour Samantha, Olmstead Mary C
Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.
Behav Pharmacol. 2013 Jun;24(3):207-13. doi: 10.1097/FBP.0b013e3283618ac8.
In addition to sensory disturbances, neuropathic pain is associated with an ongoing and persistent negative affective state. This condition may be reflected as altered sensitivity to rewarding stimuli. We examined this hypothesis by testing whether the rewarding properties of morphine are altered in a rat model of neuropathic pain. Neuropathic pain was induced by chronic constriction of the common sciatic nerve. Drug reward was assessed using an unbiased, three-compartment conditioned place preference (CPP) paradigm. The rats underwent two habituation sessions beginning 6 days after surgery. Over the next 8 days, they were injected with drug or vehicle and were confined to one CPP compartment for 30 min. On the following test day, the rats had access to all three compartments for 30 min. Consistent with the literature, systemic administration of morphine dose-dependently increased the CPP in pain-naive animals. In rats with neuropathic pain, however, the dose-dependent effects of morphine were in a bell-shaped curve, with a low dose of morphine (2 mg/kg) producing a greater CPP than a higher dose of morphine (8 mg/kg). In a separate group of animals, acute administration of morphine reversed mechanical allodynia in animals with neuropathic pain at the same doses that produced a CPP. The increased potency of systemic morphine to produce a CPP in animals with neuropathic pain suggests that the motivation for opioid-induced reward is different in the two states.
除感觉障碍外，神经性疼痛还与持续存在的负面情感状态相关。这种情况可能表现为对奖赏性刺激的敏感性改变。我们通过测试在神经性疼痛大鼠模型中吗啡的奖赏特性是否改变来检验这一假设。通过慢性结扎坐骨神经诱导神经性疼痛。使用无偏倚的三室条件性位置偏爱（CPP）范式评估药物奖赏。大鼠在手术后6天开始进行两次适应训练。在接下来的8天里，它们被注射药物或赋形剂，并被限制在一个CPP隔室中30分钟。在接下来的测试日，大鼠可以进入所有三个隔室30分钟。与文献一致，在未患疼痛的动物中，全身给予吗啡剂量依赖性地增加了CPP。然而，在患有神经性疼痛的大鼠中，吗啡的剂量依赖性效应呈钟形曲线，低剂量吗啡（2mg/kg）比高剂量吗啡（8mg/kg）产生更大的CPP。在另一组动物中，急性给予吗啡在产生CPP的相同剂量下逆转了患有神经性疼痛动物的机械性异常性疼痛。全身给予吗啡在患有神经性疼痛的动物中产生CPP的效力增加表明，在这两种状态下阿片类药物诱导奖赏的动机是不同的。
