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22KS-014
The effect of ketamine on endoplasmic reticulum stress in rat with neuropathic pain
Ji Min Choi, M.D., Liyun Piao, B.Med.1, Eun-Hye Seo, Ph.D.2, Seung wan Hong, M.D., Woo-Chul Song, M.D.3, Ph.D., Seong-Hyop Kim, M.D., Ph.D.

Department of Anesthesiology and Pain medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Background: The study was designed to investigate the effect of ketamine on endoplasmic reticulum (ER) stress in the rat with neuropathic pain (NP).
Methods: Through ligation and transection of sciatic nerve, NP was conducted in the rats. After confirmation of NP, the animals were randomly divided into Ketamine and Control groups. Ketamine 50 mg/kg for Ketamine group and same volume of normal saline for Control group were injected, respectively, on 15, 18 and 21 days after the surgery for NP. On 21 days after the surgery for NP, the expressions of N-methyl-D-aspartate (NMDA) receptor subtype 2B (NR2B) and ER stress markers in the spinal cord, L5, were evaluated. Intra-group differences and inter-group differences were analyzed with unpaired t-test and two-way repeated ANOVA. A p-value < 0.05 was considered significant.
Results: Ipsilateral side for the surgery in Ketamine group had the less sensitive to mechanical stimulations. The expression of NR2B at ipsilateral side for the surgery in Ketamine group had the significant lower expression, compared with Control group (31.08 ¡¾ 0.74% at Control group, vs. 18.93 ¡¾ 1.40% in Ketamine group, p < 0.05). All markers for ER stress at ipsilateral side for the surgery in both groups had the higher expression than contralateral side. The expression of activating transcription factor-6 (ATF-6) at ipsilateral side for the surgery in Ketamine group had the significant lower expression, compared with Control group (p < 0.05).
Conclusion: Systemic administration of ketamine inhibited the expression of NMDA receptor and showed the improvement of symptoms for NP. The effect of ketamine was associated with inhibition for the expression of ATF-6, among the markers of ER stress.

References
1. Inquimbert P, Moll M, Latremoliere A, Tong CK, Whang J, Sheehan GF, Smith BM, Korb E, Athis CD, Hof PR, Scholz J. NMDA receptor activation underlies the loss of spinal dorsal horn neurons and the transition to persistent pain after peripheral nerve injury. Cell Rep 2018; 23: 2678-89.
2. Ahn MJ, Kim HJ, Lee WH, Shin YS, Lee JU. Neuropathic pain management with NMDA receptor antagonist (Ketamine) in pain clinic. Korean J Pain 1998; 11: 294-8.