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当前关于伤害性热痛的认识主要局限于温度感受器,如表达在背根神经节(DRG)伤害性感觉神经元上的瞬时受体电位阳离子通道(TRPV1)。但是温度感受器的缺失仅部分地影响热痛,表明热痛的产生和调控还存在未知机制。我们发现在小鼠DRG神经元中条件性敲除胞浆型成纤维细胞13因子(FGF),导致热痛选择性缺失;敲除了FGF13的DRG神经元,伤害性热刺激不能诱发动作电位的持续发放;FGF13与钠通道(Nav)1.7作用可以促进热痛的传导,增强伤害性热刺激诱发的Nav1.7电流并维持Nav1.7上膜过程,进而维持动作电位的持续发放。打破FGF13和Nav1.7相互作用抑制了热刺激诱发的动作电位和痛反射行为。因此,不同于温度感受器,FGF13和Nav1.7的相互作用对于维持热痛信号的产生和传递是至关重要的。
Current understanding of nociceptive pain is limited primarily to thermoreceptors such as the transient receptor potential cation channel (TRPV1) expressed on the nociceptive sensory neurons of the dorsal root ganglion (DRG). However, the absence of thermoreceptors only partially affects the heat pain, suggesting that there is an unknown mechanism for the generation and regulation of heat pain. We found that conditional knockout of cytosolic fibroblast 13 factor (FGF) in mouse DRG neurons resulted in the selective loss of thermal pain; knockout of DRG neurons of FGF13, nociceptive thermal stimulation did not induce sustained action potentials FGF13 and sodium channel (Nav) 1.7 can promote the conduction of heat pain, enhance the nociceptive heat-induced Nav1.7 current and maintain the Nav1.7 membrane process, thereby maintaining the continuous release of action potential. Breaking the interaction between FGF13 and Nav1.7 suppresses the action potentials and pain reflex behaviors induced by thermal stimulation. Therefore, unlike thermoreceptors, the interaction of FGF13 and Nav1.7 is crucial to maintain the production and delivery of thermal pain signals.