Peripheral CRH orchestrates neuropathic pain through transcriptional control by SMAD1 and spinal CRHR2 activation

Corticotropin-releasing hormone (CRH) is associated with the central neural circuits involved in stress and pain. Here, we identified a peripheral CRH–mediated signaling axis in dorsal root ganglion (DRG) and spinal neurons underlying neuropathic pain.

Spared nerve injury (SNI) in male mice increased the abundance of CRH in small- and medium-diameter DRG neurons, specifically within their central terminals in the spinal dorsal horn. DRG-specific knockdown of CRH alleviated neuropathic pain. SNI increased Crh expression by inducing the binding of the transcription factor SMAD1 to the Crh promoter.