Peripheral neuropathic pain (PNP) is a form of chronic pain that is challenging to treat. It arises from a neuronal lesion that triggers intricate molecular and biochemical changes in the nociceptive system. Cellular metabolites, which are products or substrates of cellular activity, play crucial roles in various functions. An imbalance in cellular metabolism is implicated in the pathophysiology of numerous diseases.

We hypothesize that peripheral neuropathy induces a metabolic disturbance in the components of the nociceptive system. Among the cellular metabolites, succinate—a Krebs cycle metabolite—and its receptor, GPR91, have been associated with the progression of certain pathologies. Our preliminary data suggest that succinate exhibits pro-nociceptive effects, and mice deficient in GPR91 appear to be resistant to the development of Diabetic Neuropathic Pain (DNP).

This project aims to investigate the relationship between succinate and GPR91 in the development of DNP. The findings are expected to offer critical insights into the deregulation of cellular energy and its implications in chronic pain, potentially contributing to the creation of more effective analgesics.