Injury-induced activation of the endocannabinoid system promotes axon regeneration

Regeneration after a peripheral nerve injury still remains a challenge, due to the limited regenerative potential of axons after injury. While the endocannabinoid system (ECS) has been widely studied for its neuroprotective and analgesic effects, its role in axonal regeneration and during the conditioning lesion remains unexplored. In this study, we observed that a peripheral nerve injury induces axonal regeneration through an increase in the endocannabinoid tone. We also enhanced the regenerative capacity of dorsal root ganglia (DRG) neurons through the inhibition of endocannabinoid degradative enzyme MAGL or a CB1R agonist. Our results suggest that the ECS, via CB1R and PI3K-pAkt pathway activation, plays an important role in promoting the intrinsic regenerative capacity of sensory neurons after injury. [Display omitted] •Nerve injury induces activation of the ECS•MAGL inhibition enhances neurite outgrowth•CB1R agonist improves intrinsic regenerative capacity of sensory neurons•Injury-activated ECS promotes neuron regrowth via PI3K-pAkt Drugs; Molecular medicine; Clinical neuroscience