Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission.
Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission.
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感觉神经节内的局部 GABA 信号传导控制外周伤害性传递。
DOI：
10.1172/jci86812
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发表时间：
2017-05-01
期刊：
影响因子：
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通讯作者：
Gamper N
中科院分区：
文献类型：
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作者：
Du X;Hao H;Yang Y;Huang S;Wang C;Gigout S;Ramli R;Li X;Jaworska E;Edwards I;Deuchars J;Yanagawa Y;Qi J;Guan B;Jaffe DB;Zhang H;Gamper N
躯体感觉信息的整合通常被认为是中枢神经系统（CNS）的功能。在这里，我们描述了啮齿动物外周感觉神经节内的全功能GABA能通讯，并表明它可以调节从外周感觉神经到CNS的疼痛相关信号的传输。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，感觉神经元释放GABA响应去极化。GABA或GABA再摄取抑制剂在感觉神经节的体内局灶性输注显著降低了急性外周诱导的伤害性感受，并减轻了神经性疼痛和炎性疼痛。此外，局部应用GABA受体拮抗剂的感觉神经节触发或加剧外周诱导的伤害性感受。我们还证明，化学或光遗传去极化的GABA能背根神经节神经元在体内减少急性和慢性外周诱导的伤害性感受。从机制上讲，GABA的去极化的感觉神经元胞体的大部分，但产生了净抑制效应的伤害性传递由于在伤害性纤维的T接头的过滤效果。我们的研究结果表明，外周躯体感觉神经节是迄今为止未被充分认识的躯体感觉信号整合的部位，并为治疗干预提供了潜在的靶点。
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.