AstraZeneca R&D Montréal, 7171 Frédérick-Banting, Ville Saint-Laurent, Québec, Canada H4S 1Z9.
Eur J Pain. 2010 May;14(5):503-9. doi: 10.1016/j.ejpain.2009.08.010. Epub 2009 Dec 5.
Although many types of nerve damage can cause neuropathic pain, there are substantial commonalities in neuropathic pain symptoms, and patients can be divided into sub-groups based on their symptom profile rather than etiology. Mechanism-based treatment suggests that pharmacotherapy should be chosen be based shared commonalities of symptoms rather than etiology. The aim of the present study was to determine whether type of injury (etiology) or behavioral endpoint (symptom) is a better predictor of pharmacological responsivity in the most commonly used rodent models of neuropathic pain. We used the chronic constriction injury (CCI) model to directly compare the temporal and pharmacological characteristics of four different types of evoked stimuli; heat, pressure, acetone cooling and punctate mechanical. We then compared heat hyperalgesia and mechanical allodynia endpoints across etiologies using the spinal nerve ligation (SNL) model. Evoked pain responses in both models had strikingly different temporal characteristics. We then tested three standard therapies for neuropathic pain from different drug classes, oxycodone, gabapentin, and amitriptyline. Notably, regardless of the model tested, or the time of onset, common endpoints showed near-identical pharmacological responses, and not all endpoints were equally sensitive to drug intervention within one model. Hypersensitivity to heat and pressure were highly responsive to oxycodone, gabapentin, and amitriptyline; whereas cold and mechanical allodynia were more difficult to reverse. Moreover, CCI- and SNL-induced mechanical allodynia was completely insensitive to amitriptyline treatment. We conclude that regardless of model and time course of presentation, different symptoms of peripheral neuropathy have unique pharmacological responses.
尽管许多类型的神经损伤都可能导致神经性疼痛，但神经性疼痛的症状有很多共同之处，而且患者可以根据症状特征而非病因来分为亚组。基于机制的治疗表明，应该根据症状的共同特征而不是病因来选择药物治疗。本研究的目的是确定损伤类型（病因）或行为终点（症状）是否更能预测神经性疼痛最常用的啮齿动物模型中的药物反应性。我们使用慢性缩窄性损伤（CCI）模型来直接比较四种不同类型诱发刺激的时间和药物特征：热、压、丙酮冷却和机械单点刺激。然后，我们使用脊神经结扎（SNL）模型比较了热痛觉过敏和机械性痛觉过敏终点在不同病因之间的表现。两种模型中的诱发疼痛反应都具有明显不同的时间特征。然后，我们测试了三种来自不同药物类别的标准神经性疼痛治疗药物：羟考酮、加巴喷丁和阿米替林。值得注意的是，无论测试的模型如何，或发病时间如何，共同的终点都显示出几乎相同的药物反应，而且并非所有终点在一种模型中对药物干预的敏感性都相同。对热和压的超敏反应对羟考酮、加巴喷丁和阿米替林高度敏感；而冷和机械性痛觉过敏则更难逆转。此外，CCI 和 SNL 诱导的机械性痛觉过敏对阿米替林治疗完全不敏感。我们得出结论，无论模型和表现时间如何，周围神经病变的不同症状都有独特的药物反应。
