Esketamine alleviates trigeminal neuralgia and anxiety-like behaviors in mice by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis.
Brain research bulletin August 1, 2026 Rui Dong, Jiaxin Liu, Yumei Shen et al.
In a mouse model of trigeminal neuralgia (TN) that also shows anxiety-like behavior, esketamine (ES) given for five days dose-dependently reduced pain and anxiety. TN caused damage to neurons in the hippocampus and increased levels of the necroptosis pathway proteins RIPK1, RIPK3, and MLKL. ES treatment reversed these changes, protecting neurons and restoring dendritic spines. Adding a necroptosis activator blocked ES's effects, confirming that ES works by inhibiting the RIPK1/RIPK3/MLKL pathway. The findings highlight necroptosis as a key mechanism linking TN pain to emotional disorders and suggest ES could be repurposed as a treatment for both pain and anxiety in TN.