Wieseler-Frank Julie, Maier Steven F, Watkins Linda R
Department of Psychology & Center for Neuroscience, University of Colorado at Boulder, Boulder, CO 80309-0345, USA.
Brain Behav Immun. 2005 Mar;19(2):104-11. doi: 10.1016/j.bbi.2004.08.004.
This review examines recently recognized roles of immunological processes in pain modulation and explores the potential implications of these immunologically derived phenomena for human chronic pain control. The focus is an examination of how activation of immune-like glial cells within the spinal cord can amplify pain by modulating the excitability of spinal neurons. Such glially driven enhancement of pain can be physiological, as occurs in response to peripheral infection or inflammation. Here, immune-to-brain-to-spinal cord communication leads to pain enhancement (hyperalgesia) as one component of the well-characterized sickness response. This sickness-induced hyperalgesia, like many sickness responses, is mediated by the activation of glia and the consequent release of proinflammatory cytokines. However, glially driven pain can also occur under pathological conditions, such as occurs following peripheral nerve inflammation or trauma. Here, immune- and trauma-induced alterations in peripheral nerve function lead to the release of substances within the spinal cord that trigger the activation of glia. Evidence is reviewed that such pathologically driven glial activation is associated with enhanced pain states of diverse etiologies and that such pain facilitation is driven by glial release of proinflammatory cytokines and other neuroexcitatory substances. This recently recognized role of spinal cord glia and glially derived proinflammatory cytokines as powerful modulators of pain is exciting as it may provide novel approaches for controlling human chronic pain states that are poorly controlled by currently available therapies.
本综述探讨了免疫过程在疼痛调节中最近被认识到的作用，并探讨了这些免疫源性现象对人类慢性疼痛控制的潜在影响。重点是研究脊髓内免疫样胶质细胞的激活如何通过调节脊髓神经元的兴奋性来放大疼痛。这种由胶质细胞驱动的疼痛增强可能是生理性的，如在对周围感染或炎症的反应中发生的那样。在这里，免疫-脑-脊髓通讯导致疼痛增强（痛觉过敏），这是特征明确的疾病反应的一个组成部分。这种疾病诱导的痛觉过敏，与许多疾病反应一样，是由胶质细胞的激活和随之而来的促炎细胞因子的释放介导的。然而，由胶质细胞驱动的疼痛也可能在病理条件下发生，例如在周围神经炎症或创伤后发生。在这里，免疫和创伤引起的周围神经功能改变导致脊髓内物质的释放，从而触发胶质细胞的激活。有证据表明，这种由病理驱动的胶质细胞激活与多种病因的疼痛增强状态有关，并且这种疼痛促进是由胶质细胞释放促炎细胞因子和其他神经兴奋性物质驱动的。脊髓胶质细胞和胶质细胞衍生的促炎细胞因子作为疼痛的强大调节因子的这一最近被认识到的作用令人兴奋，因为它可能为控制目前可用疗法控制不佳的人类慢性疼痛状态提供新的方法。
