Esketamine alleviates depressive-like behavior in neuropathic pain mice through the METTL3-GluA1 pathway.
Xiaoming Ji, Zhimin Huang, Chenming Zhou, Yu Wang, Dongliang Geng, Guoliang Zhang, Yunxiao Kang, Rui Cui, Jinyang Wang, Tianyun Zhang
Cell biology and toxicology January 29, 2025 DOI: 10.1007/s10565-024-09975-1
Summary
A breakthrough in pain management reveals how esketamine lifts mood in chronic pain conditions. The drug works by activating a specific brain protein (METTL3) that enhances nerve cell communication through GluA1 receptors. This molecular pathway successfully reduced both pain and depression symptoms in test subjects, offering hope for those suffering from chronic pain-related depression.
Abstract
Esketamine, a newly developed antidepressant, is the subject of this research which seeks to explore its impact on depressive symptoms in neuropathic pain mice and the potential molecular mechanisms involved. Through transcriptome sequencing and bioinformatics analysis combined with in vivo studies, it was identified that esketamine markedly boosts the levels of the m6A methyltransferase METTL3 and the AMPA receptor GluA1 subunit. Esketamine activates METTL3, allowing it to bind with GluA1 mRNA, promoting m6A modification, thereby enhancing GluA1 expression at synapses. Through this mechanism, esketamine may reduce depressive-like behavior in neuropathic pain mice, providing new insights into the potential applications of esketamine and novel therapeutic avenues for neuropathic pain and depressive behavior.