TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice
TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice
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DOI：
10.1016/j.celrep.2013.09.013
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发表时间：
2013-10-01
期刊：
影响因子：
8.8
通讯作者：
Moqrich, Aziz
中科院分区：
文献类型：
--
作者：
Delfini, Marie-Claire;Mantilleri, Annabelle;Moqrich, Aziz
C-低阈值机械感受器（C-LTMR）是C-无髓鞘初级感觉神经元中独特的。这些神经元传达触觉的两个相反方面：愉悦感和损伤引起的机械疼痛感。在这里，我们表明TAFA 4是C-LTMR的特异性标志物。遗传标记结合电生理记录表明，TAFA 4+神经元具有机械伤害感受器的内在特性。TAFA 4缺失小鼠在炎症和神经损伤后表现出增强的机械和化学超敏性以及脊髓板层III神经元的兴奋性增加，这可以通过鞘内或浴内应用重组TAFA 4蛋白来逆转。在野生型C57/B16小鼠中，鞘内给予TAFA 4强烈逆转角叉菜胶诱导的机械超敏反应，表明TAFA 4在疼痛缓解中的有效镇痛作用。我们的数据提供了关于C-LTMR衍生的TAFA 4如何调节神经元兴奋性和控制躯体感觉阈值的见解。
C-low-threshold mechanoreceptors (C-LTMRs) are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.