Department of Pharmacology and Therapeutics, NCBES Neuroscience Cluster and Centre for Pain Research, National University of Ireland, Galway, University Road, Galway, Ireland.
Immunobiology. 2010 Aug;215(8):629-46. doi: 10.1016/j.imbio.2009.05.011. Epub 2009 Jul 17.
The stress response is associated with a broad spectrum of physiological and behavioural effects including hypothalamo-pituitary-adrenal (HPA) axis activation, altered central nervous system activity, neuroimmune alterations, anxiety- and depressive-like behaviour and analgesia. While the acute stress response has essential survival value, chronic stress and dysfunction of the stress response can be maladaptive, contributing to the development and severity of psychiatric and pain disorders. The endogenous cannabinoid (endocannabinoid) system has emerged as an important lipid signalling system playing a key role in mediating and/or modulating behavioural, neurochemical, neuroendocrine, neuroimmune and molecular responses to stress. The weight of evidence, reviewed here, points largely to a system which serves to constrain HPA axis activity, facilitate adaptation or habituation of HPA axis and behavioural responses to stress, reduce anxiety- and depressive-like behaviour and mediate analgesic responses to unconditioned or conditioned stress. Possible involvement of the immune system and associated signalling molecules (e.g. cytokines) in endocannabinoid-mediated modulation of neuroendocrine and behavioural responses to stress is considered. The goal now should be to exploit our understanding of the role of the endocannabinoid system in fundamental stress physiology and pathophysiological processes to better understand and treat a range of stress-related disorders including anxiety, depression and pain.
应激反应与广泛的生理和行为效应有关，包括下丘脑-垂体-肾上腺 (HPA) 轴激活、中枢神经系统活动改变、神经免疫改变、焦虑和抑郁样行为以及镇痛。虽然急性应激反应具有重要的生存价值，但慢性应激和应激反应功能障碍可能是适应不良的，导致精神和疼痛障碍的发展和严重程度。内源性大麻素（内源性大麻素）系统已成为一种重要的脂质信号系统，在调节和/或调节对压力的行为、神经化学、神经内分泌、神经免疫和分子反应方面发挥着关键作用。这里回顾的大量证据表明，该系统主要用于限制 HPA 轴的活动，促进 HPA 轴和对压力的行为反应的适应或习惯化，减少焦虑和抑郁样行为，并介导对非条件或条件应激的镇痛反应。还考虑了免疫系统和相关信号分子（例如细胞因子）在内源性大麻素介导的对压力的神经内分泌和行为反应的调节中的可能参与。现在的目标应该是利用我们对内源性大麻素系统在基本应激生理学和病理生理学过程中的作用的理解，以更好地理解和治疗一系列与应激相关的疾病，包括焦虑、抑郁和疼痛。
