The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury

After spinal cord injury, the interruption of axonal tracts leads to disconnection of neurons and loss of function. This study showed that nociceptin/ ORL1 signaling limits neural repair. Treatment with an ORL1 antagonist in a clinically relevant time window enhanced neural repair and recovery of mice after SCI.

• 1
  ORL1 expression promoted glycosylation and surface expression of NgR1 to mediate inhibition of axonal regeneration by myelin-associated inhibitors.
• 2
  Nociceptin/ORL1 signaling through the RhoA/ROCK pathway inhibited axonal regeneration independently of NgR1.
• 3
  Administration of the ORL1 antagonist J113397 after hemisection SCI in WT mice increased raphespinal axon sprouting caudal to injury site.