Bjurstrom Martin F, Giron Sarah E, Griffis Charles A
Cousins Center for Psychoneuroimmunology, University of California, Los Angeles (UCLA), Los Angeles, California, U.S.A.
Department of Anesthesiology, University of California, Los Angeles (UCLA), Los Angeles, California, U.S.A.
Pain Pract. 2016 Feb;16(2):183-203. doi: 10.1111/papr.12252. Epub 2014 Oct 29.
Chronic pain is a prevalent and debilitating condition, conveying immense human burden. Suffering is caused not only by painful symptoms, but also through psychopathological and detrimental physical consequences, generating enormous societal costs. The current treatment armamentarium often fails to achieve satisfying pain relief; thus, research directed toward elucidating the complex pathophysiological mechanisms underlying chronic pain syndromes is imperative. Central neuroimmune activation and neuroinflammation have emerged as driving forces in the transition from acute to chronic pain, leading to central sensitization and decreased opioid efficacy, through processes in which glia have been highlighted as key contributors. Under normal conditions, glia exert a protective role, but in different pathological states, a deleterious role is evident--directly and indirectly modulating and enhancing pain transmission properties of neurons, and shaping synaptic plasticity in a dysfunctional manner. Cytokines and neurotrophic factors have been identified as pivotal mediators involved in neuroimmune activation pathways and cascades in various preclinical chronic pain models. Research confirming these findings in humans has so far been scarce, but this comprehensive review provides coherent data supporting the clear association of a mechanistic role of altered central cytokines and neurotrophic factors in a number of chronic pain states despite varying etiologies. Given the importance of these factors in neuropathic and inflammatory chronic pain states, prospective therapeutic strategies, and directions for future research in this emerging field, are outlined.
慢性疼痛是一种普遍且使人衰弱的病症，带来了巨大的人类负担。痛苦不仅由疼痛症状引起，还源于心理病理学和有害的身体后果，产生了巨大的社会成本。当前的治疗手段常常无法实现令人满意的疼痛缓解；因此，致力于阐明慢性疼痛综合征潜在复杂病理生理机制的研究势在必行。中枢神经免疫激活和神经炎症已成为从急性疼痛向慢性疼痛转变的驱动力，通过胶质细胞被突出视为关键促成因素的过程，导致中枢敏化和阿片类药物疗效降低。在正常情况下，胶质细胞发挥保护作用，但在不同的病理状态下，其有害作用明显——直接和间接调节并增强神经元的疼痛传递特性，并以功能失调的方式塑造突触可塑性。在各种临床前慢性疼痛模型中，细胞因子和神经营养因子已被确定为参与神经免疫激活途径和级联反应的关键介质。迄今为止，在人类中证实这些发现的研究很少，但这篇全面综述提供了连贯的数据，支持尽管病因各异，但中枢细胞因子和神经营养因子的机制作用与多种慢性疼痛状态之间存在明确关联。鉴于这些因素在神经性和炎症性慢性疼痛状态中的重要性，本文概述了前瞻性治疗策略以及这一新兴领域未来的研究方向。
