The Thalamic Paraventricular Nucleus-Prefrontal Cortex Neural Circuit in Hyperalgesia Associated with Diabetic Painful Neuropathy

• 1、The Second Affiliated Hospital of Soochow University,suzhou 21500

Abstract：Diabetic peripheral neuropathy (DPN) is one of the most common complications in patients with diabetes and seriously affects their quality of life. In recent years, research on the pathogenesis of DPN has increasingly revealed the important role of the central nervous system in pain perception. This study aims to investigate the neural mechanisms of DPN, focusing on the role of glutamatergic neurons in the paraventricular thalamus (PVT) and the prelimbic cortex (PrL). A DPN mouse model was established using streptozotocin (STZ) induction. In vivo fiber photometry was used to monitor the response of glutamatergic neurons in the PVT and PrL to nociceptive stimuli. Optogenetic and chemogenetic approaches were employed to specifically regulate these neurons and assess their effects on pain behaviors. The results showed that DPN mice exhibited significant mechanical hypersensitivity, accompanied by markedly increased activity of glutamatergic neurons in the PVT and PrL. Interventions targeting glutamatergic neurons in the PVT and PrL significantly alleviated pain behaviors in DPN mice. Further studies confirmed the critical role of the PVT-PrL neural circuit in DPN-related pain modulation. This research provides new insights into the neural circuitry underlying DPN and offers potential therapeutic targets for clinical intervention, suggesting that targeting the PVT and PrL may provide novel strategies for managing chronic pain.

Keywords： neuroscience diabetic painful neuropathy paraventricular thalamic nucleus prefrontal cortex neural circui