c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy
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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000607311Publication status
publishedExternal links
Journal / series
Cell ReportsVolume
Pages / Article No.
Publisher
Cell PressSubject
spinal cord; corticospinal tract; neuropathic pain; deep dorsal horn; allodynia; allokinesis; protein kinase C gamma; spinal interneurons; nociceptionOrganisational unit
03742 - Zeilhofer, Hanns U. / Zeilhofer, Hanns U.
More
Show all metadata