科学家报告说一种和免疫系统有关的分子可能有助于调节神经性疼痛。Kazuhide Inoue及其同事发现，信号传导分子干扰素gamma [IFN-gamma]刺激中枢神经系统的受体，这会导致大鼠模型的持久疼痛。
此前的研究表明神经性疼痛——一种使人衰弱的疾病，通常发生在神经损伤之后，而且可能导致即便最轻微的接触也能带来剧痛——可能是由脊髓的痛觉神经元和称为小胶质细胞的脊髓免疫细胞的异常引起的。
这组作者证明了IFN-gamma活化了小胶质细胞，而且它是制造神经系统疼痛必需的；相反，抑制这种信号就能防止小鼠模型出现神经相关的疼痛。小鼠没有产生IFN-gamma受体表明了小胶质细胞活化和神经性疼痛的减少，尽管它们表现出了正常的生理疼痛反应。这组作者说，瞄准这些受体可能为神经性疼痛提供了一个保持生理疼痛反应不受影响的另一种疗法。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS April 20, 2009, doi: 10.1073/pnas.0810420106
IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain
Makoto Tsuda,1, Takahiro Masuda,1, Junko Kitano, Hiroshi Shimoyama, Hidetoshi Tozaki-Saitoh and Kazuhide Inoue,2
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
1M.T. and T.M. contributed equally to this work.
Neuropathic pain, a highly debilitating pain condition that commonly occurs after nerve damage, is a reflection of the aberrant excitability of dorsal horn neurons. This pathologically altered neurotransmission requires a communication with spinal microglia activated by nerve injury. However, how normal resting microglia become activated remains unknown. Here we show that in naive animals spinal microglia express a receptor for the cytokine IFN-γ (IFN-γR) in a cell-type-specific manner and that stimulating this receptor converts microglia into activated cells and produces a long-lasting pain hypersensitivity evoked by innocuous stimuli (tactile allodynia, a hallmark symptom of neuropathic pain). Conversely, ablating IFN-γR severely impairs nerve injury-evoked microglia activation and tactile allodynia without affecting microglia in the contralateral dorsal horn or basal pain sensitivity. We also find that IFN-γ-stimulated spinal microglia show up-regulation of Lyn tyrosine kinase and purinergic P2X4 receptor, crucial events for neuropathic pain, and genetic approaches provide evidence linking these events to IFN-γR-dependent microglial and behavioral alterations. These results suggest that IFN-γR is a key element in the molecular machinery through which resting spinal microglia transform into an activated state that drives neuropathic pain.
