Comment on: Exploring the mechanism of ropivacaine in alleviating neuropathic pain via the mTOR-PKM2/STAT3-H4K12 lactylation axis.

We read with great interest the study by Chen et al. investigating ropivacaine as a potential treatment for neuropathic pain (NP) via the mTOR-PKM2/STAT3-H4K12 lactylation axis. Using chronic constriction injury (CCI) mice and BV-2 microglia, the authors convincingly demonstrate that ropivacaine reduces hyperalgesia, suppresses mTOR signaling, lowers PKM2 and p-STAT3 levels, inhibits microglial M1 polarization, and diminishes histone H4K12 lactylation (H4K12la) and oxidative stress. This work provides novel insights into metabolic-epigenetic crosstalk in neuroinflammation and pain. Despite these strengths, we believe several critical issues need clarification to strengthen the mechanistic causality and translational relevance.