Department of Oral and Maxillofacial Surgery and Division of Neuroscience, University of California, San Francisco, CA 94143-0440, USA.
Trends Neurosci. 2009 Dec;32(12):611-8. doi: 10.1016/j.tins.2009.07.007. Epub 2009 Sep 24.
The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain. We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines. This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability. We discuss the impact of this discovery on our understanding of, and ultimately our ability to treat, a variety of enigmatic and debilitating pain conditions, including those associated with repetitive injury, and generalized pain conditions, such as fibromyalgia.
从急性疼痛状态向慢性疼痛状态的转变可能是改善致残性疼痛临床治疗的研究中最具挑战性的问题。我们描述了一种新近发现的初级传入伤害性神经纤维（伤害感受器）神经元可塑性机制，通过该机制，急性炎症损伤或环境应激源可引发伤害感受器对炎症细胞因子的长期超敏反应。这种现象被称为“痛觉敏化启动”，依赖于蛋白激酶 C 的 ε 同工型（PKCε）和介导细胞因子诱导的伤害感受器过度兴奋的细胞内信号转导途径的转换。我们讨论了这一发现对我们理解和最终治疗各种神秘和致残性疼痛状况的影响，包括与重复性损伤相关的状况和全身性疼痛状况，如纤维肌痛。
