In this study, we established a PTX model to examine the effects of S-ketamine on pyramidal neurons in the prelimbic cortex (PrL) and the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway, specifically investigating the role of metabotropic glutamate receptor 5 (mGluR5).<h4>Methods</h4>A PTX-induced peripheral neuropathy and pain-related anxiety mouse model was established by intraperitoneal injection of PTX. Here, GRM5 is linked to peripheral neuropathy.