The Effect of Ketamine on Endoplasmic Reticulum Stress in Rats with Neuropathic Pain †

This study aimed to investigate the effects of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on endoplasmic reticulum (ER) stress in rats with neuropathic pain (NP). NP was induced in rats through ligation and transection of the sciatic nerve. After confirmation of NP, the animals were randomly divided into ketamine and control groups. The ketamine group was administered 50 mg/kg of ketamine at 15, 18, and 21 days after surgery. The expression of NMDA receptor subtype 2B (NR2B) and ER stress markers in the spinal cord (L5) was evaluated. The ipsilateral side of the surgery in the ketamine group was less sensitive to mechanical and cold stimulations. The expression of NR2B on the ipsilateral side was significantly lower in the ketamine group than in the control group (18.93 ± 1.40% vs. 31.08 ± 0.74%, p < 0.05). All markers for ER stress on the ipsilateral side of the surgery in both groups had higher expression than those on the contralateral side. The expression of activating transcription factor-6 (ATF-6) on the ipsilateral side was significantly lower in the ketamine group than in the control group (p < 0.05). Systemic administration of ketamine inhibited the expression of NMDA receptors and improved NP symptoms. Among the markers of ER stress, the therapeutic effect of ketamine is associated with the inhibition of ATF-6 expression.