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Identification of Spinal Circuits Transmitting and Gating Mechanical Pain

Overview
Journal Cell
Publisher Cell Press
Specialty Cell Biology
Date 2014 Dec 4
PMID 25467445
Citations 295
Authors
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Abstract

Pain information processing in the spinal cord has been postulated to rely on nociceptive transmission (T) neurons receiving inputs from nociceptors and Aβ mechanoreceptors, with Aβ inputs gated through feed-forward activation of spinal inhibitory neurons (INs). Here, we used intersectional genetic manipulations to identify these critical components of pain transduction. Marking and ablating six populations of spinal excitatory and inhibitory neurons, coupled with behavioral and electrophysiological analysis, showed that excitatory neurons expressing somatostatin (SOM) include T-type cells, whose ablation causes loss of mechanical pain. Inhibitory neurons marked by the expression of dynorphin (Dyn) represent INs, which are necessary to gate Aβ fibers from activating SOM(+) neurons to evoke pain. Therefore, peripheral mechanical nociceptors and Aβ mechanoreceptors, together with spinal SOM(+) excitatory and Dyn(+) inhibitory neurons, form a microcircuit that transmits and gates mechanical pain. PAPERCLIP:

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References
1.
Abraira V, Ginty D . The sensory neurons of touch. Neuron. 2013; 79(4):618-39. PMC: 3811145. DOI: 10.1016/j.neuron.2013.07.051. View

2.
Lu Y, Dong H, Gao Y, Gong Y, Ren Y, Gu N . A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia. J Clin Invest. 2013; 123(9):4050-62. PMC: 4381282. DOI: 10.1172/JCI70026. View

3.
Xu Y, Lopes C, Wende H, Guo Z, Cheng L, Birchmeier C . Ontogeny of excitatory spinal neurons processing distinct somatic sensory modalities. J Neurosci. 2013; 33(37):14738-48. PMC: 3771039. DOI: 10.1523/JNEUROSCI.5512-12.2013. View

4.
Mendell L . Constructing and deconstructing the gate theory of pain. Pain. 2013; 155(2):210-216. PMC: 4009371. DOI: 10.1016/j.pain.2013.12.010. View

5.
Bessou P, Perl E . Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol. 1969; 32(6):1025-43. DOI: 10.1152/jn.1969.32.6.1025. View