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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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