科學(xué)家報告說一種和免疫系統(tǒng)有關(guān)的分子可能有助于調(diào)節(jié)神經(jīng)性疼痛。Kazuhide Inoue及其同事發(fā)現(xiàn),，信號傳導(dǎo)分子干擾素gamma [IFN-gamma]刺激中樞神經(jīng)系統(tǒng)的受體,，這會導(dǎo)致大鼠模型的持久疼痛,。
此前的研究表明神經(jīng)性疼痛——一種使人衰弱的疾病，通常發(fā)生在神經(jīng)損傷之后,，而且可能導(dǎo)致即便最輕微的接觸也能帶來劇痛——可能是由脊髓的痛覺神經(jīng)元和稱為小膠質(zhì)細胞的脊髓免疫細胞的異常引起的,。
這組作者證明了IFN-gamma活化了小膠質(zhì)細胞，而且它是制造神經(jīng)系統(tǒng)疼痛必需的,；相反,，抑制這種信號就能防止小鼠模型出現(xiàn)神經(jīng)相關(guān)的疼痛。小鼠沒有產(chǎn)生IFN-gamma受體表明了小膠質(zhì)細胞活化和神經(jīng)性疼痛的減少,，盡管它們表現(xiàn)出了正常的生理疼痛反應(yīng),。這組作者說，瞄準這些受體可能為神經(jīng)性疼痛提供了一個保持生理疼痛反應(yīng)不受影響的另一種療法,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
