Our study demonstrates that hippocampal PRG‐1 dynamically modulates RNS‐induced hyperalgesia and anxiety through stage‐specific regulation of AMPAR GluR1/GluR2 and NMDAR GluN2A/GluN2B trafficking, which leads to synaptic remodeling via altered dendritic synaptic morphology and synaptic transmission efficacy. The gene discussed is GRIN2B; the disease is Anxiety.