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

Frezel, N.; Ranucci, M.; Foster, E.; Wende, H.; Pelczar, P.; Mendes, R.; Ganley, R.P.; Werynska, K.; d'Aquin, S.; Beccarini, C.; Birchmeier, C.; Zeilhofer, H.U.; Wildner, H.

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., Ranucci, M., Foster, E., Wende, H., Pelczar, P., Mendes, R., Ganley, R.P., Werynska, K., d'Aquin, S., Beccarini, C., Birchmeier, C., 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
ISSN:	2211-1247
Publisher:	Cell Press / Elsevier
Volume:	42
Number:	4
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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