| First Author | Frezel N | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 4 | Pages | 112295 |
| PubMed ID | 36947543 | Mgi Jnum | J:343535 |
| Mgi Id | MGI:7450653 | Doi | 10.1016/j.celrep.2023.112295 |
| Citation | Frezel N, et al. (2023) c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy. Cell Rep 42(4):112295 |
| abstractText | 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. |
