Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission
Xiaona Du, … , Hailin Zhang, Nikita Gamper
Xiaona Du, … , Hailin Zhang, Nikita Gamper
Published April 4, 2017
Citation Information: J Clin Invest. 2017;127(5):1741-1756. https://doi.org/10.1172/JCI86812.
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Research Article Neuroscience

Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission

Abstract

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.

Authors

Xiaona Du, Han Hao, Yuehui Yang, Sha Huang, Caixue Wang, Sylvain Gigout, Rosmaliza Ramli, Xinmeng Li, Ewa Jaworska, Ian Edwards, Jim Deuchars, Yuchio Yanagawa, Jinlong Qi, Bingcai Guan, David B. Jaffe, Hailin Zhang, Nikita Gamper

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Figure 9

Schematic for peripheral somatosensory integration in DRG.

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Schematic for peripheral somatosensory integration in DRG. Peripheral no...
Peripheral nociceptive stimulation triggers activity-dependent release of GABA from somatic/perisomatic compartments of afferent fibers located in DRG, which, in turn, depolarizes T-junctions of GABAA-expressing nociceptive fibers and lowers the AP safety factor at the T-junction. The latter effect results in the AP failure at the T-junction and reduced excitatory input into the spinal cord. A similar effect could be achieved by targeted delivery of GABA or GABA mimetics to the DRG or by the increasing of GABA tone with GABA reuptake inhibitor. Thus, DRG can be considered as a filter or an additional “gate” for nociceptive transmission.