Noémie Frézel, Matteo Ranucci, Edmund Foster, and their team uncover the intricate role of c-Maf-positive spinal cord neurons in neuropathic pain, in a recent publication in Cell Reports.
The team, including Hagen Wende, Pawel Pelczar, Raquel Mendes, Robert P. Ganley, Karolina Werynska, Simon d’Aquin, Camilla Beccarini, Carmen Birchmeier, Hanns Ulrich Zeilhofer, and Hendrik Wildner, have revealed the functionality of interneurons expressing the transcription factor c-Maf in dorsal horn sensory circuits. These neurons are major targets of Corticospinal tract (CST) neurons which maintain chronic neuropathic pain.
Their findings show that excitatory c-Maf (c-MafEX) neurons receive sensory input primarily from myelinated fibers and connect non-nociceptive input to nociceptive output structures. Interestingly, silencing these neurons has minimal impact in healthy mice but mitigates mechanical hypersensitivity in neuropathic mice.
The study also noted these neurons receive input from inhibitory c-Maf and parvalbumin neurons. Disturbing inhibition from these neurons results in mechanical hypersensitivity and spontaneous aversive behaviors.
This research pinpoints c-MafEX neurons as usually silent second-order nociceptors that become active in pathological pain signaling upon loss of inhibitory control. This pivotal insight advances understanding of neuropathic pain mechanisms and suggests potential pathways for therapeutic interventions.