McDougall Jason J
Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.
Biochim Biophys Acta. 2011 Apr;1812(4):459-67. doi: 10.1016/j.bbadis.2010.12.011. Epub 2010 Dec 22.
Pain is a complex biological phenomenon that encompasses intricate neurophysiological, behavioural, psychosocial and affective components. Protracted or chronic pain alerts an individual to a possible pathological abnormality and is the main reason why patients visit a primary care physician. Despite the pervasiveness of chronic pain in the population, the effectiveness of current pharmacological therapies remains woefully inadequate and prolonged treatment often leads to the development of undesirable side-effects. Since the vast majority of chronic pain originates in a specific tissue or group of tissues, it may be advantageous to target pain control in the periphery and thereby circumvent the known risks associated with non-specific systemic treatments. This review spotlights a number of promising targets for peripheral pain control including the transient receptor potential (TRP) family of neuronal ion channels, the family of proteinase activated receptors (PARs), cannabinoids, and opioids. A critical appraisal of these targets in preclinical models of disease is given and their suitability as future peripheral analgesics is discussed.
疼痛是一种复杂的生物学现象，它包含复杂的神经生理、行为、心理社会和情感成分。持续性或慢性疼痛会提醒个体可能存在病理异常，这也是患者就诊于初级保健医生的主要原因。尽管慢性疼痛在人群中普遍存在，但目前药物治疗的效果仍然差强人意，长期治疗往往会导致不良副作用的产生。由于绝大多数慢性疼痛起源于特定组织或一组组织，因此以外周疼痛控制为靶点可能具有优势，从而规避与非特异性全身治疗相关的已知风险。本综述重点介绍了一些有前景的外周疼痛控制靶点，包括神经元离子通道的瞬时受体电位（TRP）家族、蛋白酶激活受体（PARs）家族、大麻素和阿片类药物。对这些靶点在疾病临床前模型中的情况进行了批判性评估，并讨论了它们作为未来外周镇痛药的适用性。
