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Local GABAergic Signaling within Sensory Ganglia Gates Peripheral Nociceptive Transmission

Local GABAergic Signaling within Sensory Ganglia Gates Perip...

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中国神经科学学会第十二届全国学术会议

作者： Xiaona Du Han hao Caixue Wang Xinmeng Li Hailin Zhang nikita gamper Department of Pharmacology Hebei Medical University Faculty of Biological Sciences University of Leeds

Objective It is generally assumed that integration of somatosensory information is a function of the central nervous system. We aim to 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. Methods The expression of components of GABAergic circuit in DRG was tested by RT-PCR and immunofluorecent measurment. Sniffer patch and HPLC-MS methods were used to measure GABA release from DRG. Effects of DRG GABAergic circuit on pain behaviors were tested by focal application of GABA, or activating GABAergic neuron in rat/mice through optogenetic or chemogenentic approaches. Intraplantar injection of bradykinin was the method using to induce acute pain of animal. CFA injection and CCI model were used as chronic pain model. Thresholds of animal responding to mechanical and thermal stimulations were measured by Von Frey filament and Hargreaves tests. Results i) Sensory neurons express major proteins necessary for GABA synthesis and release. ii) Sensory neurons released GABA in response to depolarization. iii) In vivo focal infusion of GABA or GABA re-uptake inhibitor to sensory ganglia dramatically reduced acute peripherally-induced nociception and alleviated neuropathic and inflammatory pain. iv) Focal application of GABA receptor antagonists to sensory ganglia induced or exacerbated peripherally-induced nociception. v) Chemogenetic or optogenetic depolarization of GABAergic DRG neurons in vivo reduced acute and chronic peripherally-induced nociception. vi) 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. Conclusion Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a novel target for therapeutic i

关键词： DRG GABA pain transmission gate control theory

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