DeLeo Joyce A, Tanga Flobert Y, Tawfik Vivianne L
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Neuroscientist. 2004 Feb;10(1):40-52. doi: 10.1177/1073858403259950.
One area that has emerged as a promising therapeutic target for the treatment and prevention of chronic pain and opioid tolerance/hyperalgesia is the modulation of the central nervous system (CNS) immunological response that ensues following injury or opioid administration. Broadly defined, central neuroimmune activation involves the activation of cells that interface with the peripheral nervous system and blood. Activation of these cells, as well as parenchymal microglia and astrocytes by injury, opioids, and other stressors, leads to subsequent production of cytokines, cellular adhesion molecules, chemokines, and the expression of surface antigens that enhance a CNS immune cascade. This response can lead to the production of numerous pain mediators that can sensitize and lower the threshold of neuronal firing: the pathologic correlate to central sensitization and chronic pain states. CNS innate immunity and Toll-like receptors, in particular, may be vital players in this orchestrated immune response and may hold the answers to what initiates this complex cascade. The challenge remains in the careful perturbation of injury/opioid-induced neuroimmune activation to down-regulate this process without inhibiting beneficial CNS autoimmunity that subserves neuronal protection following injury.
作为治疗和预防慢性疼痛以及阿片类药物耐受性/痛觉过敏的一个有前景的治疗靶点，一个领域是对中枢神经系统（CNS）在损伤或阿片类药物给药后随之发生的免疫反应进行调节。广义而言，中枢神经免疫激活涉及与外周神经系统和血液相互作用的细胞的激活。这些细胞以及实质小胶质细胞和星形胶质细胞因损伤、阿片类药物及其他应激源而激活，会导致随后细胞因子、细胞黏附分子、趋化因子的产生，以及增强CNS免疫级联反应的表面抗原的表达。这种反应会导致产生众多疼痛介质，这些介质会使神经元放电敏感化并降低其阈值：这是中枢敏化和慢性疼痛状态的病理关联。特别是，CNS固有免疫和Toll样受体可能是这种精心编排的免疫反应中的关键参与者，可能为启动这一复杂级联反应的因素提供答案。挑战仍然在于如何谨慎地干扰损伤/阿片类药物诱导的神经免疫激活，以下调这一过程，同时又不抑制在损伤后对神经元起到保护作用的有益的CNS自身免疫。
