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.