Synaptic inhibition and disinhibition in the spinal dorsal horn

Progress in Molecular Biology and Translational Science
Steven A Prescott

Abstract

Nociceptive signals originating in the periphery must be transmitted to the brain to evoke pain. Rather than being conveyed unchanged, those signals undergo extensive processing in the spinal dorsal horn. Synaptic inhibition plays a crucial role in that processing. On the one hand, neuropathy and inflammation are associated with reduced spinal inhibition; on the other hand, the hypersensitivity associated with inflammatory and neuropathic pain can be reproduced by blocking inhibition at the spinal level. To understand the consequences of disinhibition and how to therapeutically reverse it, one must understand how synaptic inhibition normally operates. To that end, this chapter will discuss the structure and function of GABAA and glycine receptors together with the role of associated molecules involved in transmitter handling and chloride regulation. Mechanisms by which inhibition modulates cellular excitability will be described. The chapter will end with discussion of how inhibition goes awry under pathological conditions and what the implications are for the treatment of resulting pain.

Citations

Jan 26, 2017·Journal of Cellular Physiology·Mohammad Amin Kamaleddin
May 28, 2017·Respiratory Physiology & Neurobiology·Donatella Mutolo
Jul 13, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Elenia CinelliDonatella Mutolo
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