Muley Milind M, Krustev Eugene, McDougall Jason J
Departments of Pharmacology and Anaesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.
CNS Neurosci Ther. 2016 Feb;22(2):88-101. doi: 10.1111/cns.12486. Epub 2015 Dec 10.
While acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.
虽然急性炎症是机体对组织损伤或感染的一种自然生理反应,但慢性炎症是适应不良的,并会引发相当程度的不良疼痛。负责组织炎症的化学介质作用于伤害性神经末梢,降低神经元兴奋阈值,并分别使传入放电率敏感化,从而导致异常性疼痛和痛觉过敏的发生。动物模型有助于我们理解慢性炎性疼痛产生的病理生理机制,并使我们能够识别和验证众多镇痛候选药物。在此,我们综述一些常用的皮肤、关节和肠道炎性疼痛模型及其相对的优缺点。此外,我们描述并讨论了用于评估这些临床前模型中炎性疼痛的几种行为学和电生理学方法。尽管该领域已取得显著进展,但基础研究与将这些研究结果应用于临床实践之间仍存在差距。因此,我们需要在这些动物模型中明确内在的病理生理途径并开发新的终点指标,以提高其对人类炎性疾病的预测价值,从而设计出更安全、更有效的镇痛药。