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c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy

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Item Type:Article
Title:c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy
Creators Name:Frezel, N. and Ranucci, M. and Foster, E. and Wende, H. and Pelczar, P. and Mendes, R. and Ganley, R.P. and Werynska, K. and d'Aquin, S. and Beccarini, C. and Birchmeier, C. and Zeilhofer, H.U. and Wildner, H.
Abstract:Corticospinal tract (CST) neurons innervate the deep spinal dorsal horn to sustain chronic neuropathic pain. The majority of neurons targeted by the CST are interneurons expressing the transcription factor c-Maf. Here, we used intersectional genetics to decipher the function of these neurons in dorsal horn sensory circuits. We find that excitatory c-Maf (c-Maf(EX)) neurons receive sensory input mainly from myelinated fibers and target deep dorsal horn parabrachial projection neurons and superficial dorsal horn neurons, thereby connecting non-nociceptive input to nociceptive output structures. Silencing c-Maf(EX) neurons has little effect in healthy mice but alleviates mechanical hypersensitivity in neuropathic mice. c-Maf(EX) neurons also receive input from inhibitory c-Maf and parvalbumin neurons, and compromising inhibition by these neurons caused mechanical hypersensitivity and spontaneous aversive behaviors reminiscent of c-Maf(EX) neuron activation. Our study identifies c-Maf(EX) neurons as normally silent second-order nociceptors that become engaged in pathological pain signaling upon loss of inhibitory control.
Keywords:Spinal Cord, Corticospinal Tract, Neuropathic Pain, Deep Dorsal Horn, Allodynia, Allokinesis, Protein Kinase C Gamma, Spinal Interneurons, Nociception, Animals, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:112295
Date:21 March 2023
Official Publication:https://doi.org/10.1016/j.celrep.2023.112295
PubMed:View item in PubMed

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