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J Clin Invest. 2013 Sep;123(9):4050-62. doi: 10.1172/JCI70026. Epub 2013 Aug 27.

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia.

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1
Department of Anesthesiology and Pain Management, Xijing Hospital, Fourth Military Medical University, Xian, People's Republic of China. yanlu20008@yahoo.com

Abstract

Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated Aβ-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as "gate control" units for preventing the interaction between innocuous and nociceptive signals. However, our understanding of the neuronal circuits underlying pain signaling and modulation in the spinal DH is incomplete. Using a rat model, we have shown that the convergence of glycinergic inhibitory and excitatory Aβ-fiber inputs onto PKCγ+ neurons in the superficial DH forms a feed-forward inhibitory circuit that prevents Aβ input from activating the nociceptive pathway. This feed-forward inhibition was suppressed following peripheral nerve injury or glycine blockage, leading to inappropriate induction of action potential outputs in the nociceptive pathway by Aβ-fiber stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in vivo induced marked mechanical allodynia. Our findings identify a glycinergic feed-forward inhibitory circuit that functions as a gate control to separate the innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH. Disruption of this glycinergic inhibitory circuit after peripheral nerve injury has the potential to elicit mechanical allodynia, a cardinal symptom of neuropathic pain.

PMID:
23979158
PMCID:
PMC4381282
DOI:
10.1172/JCI70026
[Indexed for MEDLINE]
Free PMC Article
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