Metabolic reprogramming in the spinal cord drives the transition to pain chronicity.

Acute injuries can progress into painful states that endure long after healing. The mechanisms underlying this transition remain unclear, but metabolic adaptations to the bioenergy demands imposed by injury are plausible contributors. Here we show that peripheral injury activates AKT/mTORC1 in afferent segments of the mouse spinal cord, redirecting local core metabolism toward biomass production while simultaneously suppressing autophagy-mediated biomass reclamation. This metabolic shift supports neuroplasticity, but creates a resource bottleneck that depletes critical spinal cord nutrients. Preventing this depletion with a modified diet normalizes biomass generation and autophagy and halts the transition to chronic pain. This effect, observed across multiple pain models, requires activation of the nutrient sensors, sirtuin-1 and AMPK, as well as restoration of autophagy. The findings identify metabolic reprogramming and consequent autophagy suppression as key drivers of the progression to pain chronicity and highlight nutritional and pharmacological interventions that could prevent this progression after surgery or other physical traumas.