Fast synaptic inhibition in spinal sensory processing and pain control

The two amino acids GABA and glycine mediate fast inhibitory neurotransmission in different CNS areas and serve pivotal roles in the spinal sensory processing. Under healthy conditions, they limit the excitability of spinal terminals of primary sensory nerve fibers and of intrinsic dorsal horn neurons through pre- and postsynaptic mechanisms, and thereby facilitate the spatial and temporal discrimination of sensory stimuli. Removal of fast inhibition not only reduces the fidelity of normal sensory processing but also provokes symptoms very much reminiscent of pathological and chronic pain syndromes. This review summarizes our knowledge of the molecular bases of spinal inhibitory neurotransmission and its organization in dorsal horn sensory circuits. Particular emphasis is placed on the role and mechanisms of spinal inhibitory malfunction in inflammatory and neuropathic chronic pain syndromes

Modulating inhibitory ligand-gated ion channels

The glycine and γ-aminobutyric acid receptors (GlyR and GABAAR, respectively) are the major inhibitory neurotransmitter-gated receptors in the central nervous system of animals. Given the important role of these receptors in neuronal inhibition, they are prime targets of many therapeutic agents and are the object of intense studies aimed at correlating their structure and function. In this review, the structure and dynamics of these and other homologous members of the nicotinicoid superfamily are described. The modulatory actions of the major biological macromolecules that bind and allosterically affect these receptors are also discussed