Neuroscience · Nov 6, 2026

Mechanism by which metformin alleviates neuralgia in the spinal cord of diabetic rats

By Chen X, Tang MJ, Song G et al.

Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes mellitus (DM). Metformin is a widely used hypoglycemic drug that exerts anti-inflammatory and antioxidant effects. In the present study, we revealed that metformin attenuates mechanical allodynia through the AMPK pathway in the spinal cord of DM rats. Metformin intervention significantly elevated the levels of phosphorylated-AMPK (p-AMPK, the activated form of AMPK) in the L4-6 spinal dorsal horn (SDH) of DM rats. In addition, the inhibition of AMPK activation by Compound C clearly blocked metformin-mediated analgesia. Moreover, AICAR treatment significantly attenuated mechanical allodynia. Additionally, AMPK activation was observed in both neurons and glial cells. Interestingly, metformin intervention reduced the activation levels of microglia and astrocytes in the L4-6 SDH of DM rats, which suggests that AMPK plays a complicated role at the cellular level in the spinal cord. In conclusion, metformin alleviates diabetic mechanical allodynia by activating AMPK signaling in the L4-6 SDH of DM rats, and inhibits microglial and astrocytic activation. These findings support the potential use of metformin in the clinical treatment of PDN.

doi.org/10.1016/j.neuroscience.2026.11.008PubMed 42994557Interventions