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Spinal inhibitory neurotransmission in neuropathic pain

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Abstract

Nerve injury increases the spinal cord expression and/or activity of voltage- and ligand-gated ion channels, peptide receptors, and neuroimmune factors, which then drive dorsal horn neuron hyperexcitability. The intensity and duration of this central sensitization is determined by the net activity of local excitatory and inhibitory neurotransmitter systems, together with ongoing/evoked primary afferent activity and descending supraspinal control. Spinal endogenous inhibitory systems serve as opposing compensatory influences and are gaining recognition for their powerful capacity to restrain allodynia and hyperalgesia. These include numerous G protein-coupled receptors (μ- and δ-opioid, α2- adrenergic, purinergic A1, neuropeptide Y1 and Y2, cannabinoid CB1 and CB2, muscarinic M2, γ-aminobutyric acid type B, metabotropic glutamate type II–III, somatostatin) and perhaps nuclear receptors (peroxisome proliferator-activated receptor gamma). Excessive downregulation or defective compensatory upregulation of these systems may contribute to the maintenance of neuropathic pain. An increasing number of pharmacotherapeutic strategies for neuropathic pain are emerging that mimic and enhance inhibitory neurotransmission in the dorsal horn.

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  1. Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY, 40536-0298, USA

    Bradley K. Taylor

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Taylor, B.K. Spinal inhibitory neurotransmission in neuropathic pain. Current Science Inc 13, 208–214 (2009). https://doi.org/10.1007/s11916-009-0035-8

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