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

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

Blog Article

Summary: 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 click here 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 here 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.