Du Xiaona, Hao Han, Yang Yuehui, Huang Sha, Wang Caixue, Gigout Sylvain, Ramli Rosmaliza, Li Xinmeng, Jaworska Ewa, Edwards Ian, Deuchars Jim, Yanagawa Yuchio, Qi Jinlong, Guan Bingcai, Jaffe David B, Zhang Hailin, Gamper Nikita
J Clin Invest. 2017 May 1;127(5):1741-1756. doi: 10.1172/JCI86812. Epub 2017 Apr 4.
The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain. In addition, focal application of GABA receptor antagonists to sensory ganglia triggered or exacerbated peripherally induced nociception. We also demonstrated that chemogenetic or optogenetic depolarization of GABAergic dorsal root ganglion neurons in vivo reduced acute and chronic peripherally induced nociception. Mechanistically, GABA depolarized the majority of sensory neuron somata, yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at nociceptive fiber T-junctions. Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a potential target for therapeutic intervention.
体感信息的整合通常被认为是中枢神经系统（CNS）的功能。在此，我们描述了啮齿动物外周感觉神经节内完全功能性的γ-氨基丁酸（GABA）能通讯，并表明其可调节疼痛相关信号从外周感觉神经到中枢神经系统的传递。我们发现感觉神经元表达GABA合成和释放所必需的主要蛋白质，并且感觉神经元在去极化时释放GABA。在体内向感觉神经节局部注入GABA或GABA再摄取抑制剂可显著降低急性外周诱导的伤害感受，并减轻神经性和炎性疼痛。此外，向感觉神经节局部应用GABA受体拮抗剂会引发或加剧外周诱导的伤害感受。我们还证明，体内对GABA能背根神经节神经元进行化学遗传学或光遗传学去极化可降低急性和慢性外周诱导的伤害感受。从机制上讲，GABA使大多数感觉神经元胞体去极化，但由于伤害性纤维T形连接处的过滤作用，对伤害性传递产生了净抑制作用。我们的研究结果表明，外周体感神经节是一个迄今未得到充分认识的体感信号整合部位，并为治疗干预提供了一个潜在靶点。
