c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy.
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| 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-MafEX) 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-MafEX neurons has little effect in healthy mice but alleviates mechanical hypersensitivity in neuropathic mice. c-MafEX 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-MafEX neuron activation. Our study identifies c-MafEX neurons as normally silent second-order nociceptors that become engaged in pathological pain signaling upon loss of inhibitory control.
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| Authors | Noémie Frezel, Matteo Ranucci, Edmund Foster, Hagen Wende, Pawel Pelczar, Raquel Mendes, Robert P Ganley, Karolina Werynska, Simon d'Aquin, Camilla Beccarini, Carmen Birchmeier, Hanns Ulrich Zeilhofer, Hendrik Wildner |
| Journal | Cell reports (Cell Rep) Vol. 42 Issue 4 Pg. 112295 (04 25 2023) ISSN: 2211-1247 [Electronic] United States |
| PMID | 36947543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. |
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