Remifentanil-induced postoperative hyperalgesia is attenuated by inhibition of NMDAR-cADPR-RyRs signaling pathway in the spinal cord of rats

doi:10.16352/j.issn.1001-6325.2023.09.1335

Basic & Clinical Medicine ›› 2023, Vol. 43 ›› Issue (9): 1335-1340.doi: 10.16352/j.issn.1001-6325.2023.09.1335

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Remifentanil-induced postoperative hyperalgesia is attenuated by inhibition of NMDAR-cADPR-RyRs signaling pathway in the spinal cord of rats

QIAN Yue¹, WANG Fang¹, ZHANG Jing¹, XIA Tianjiao², GU Xiaoping^1*

1. Department of Anesthesiology, Nanjing Drum Tower Clinical College of Nanjing Medical University, Nanjing 210008;
2. Medical School of Nanjing University, Nanjing 210008, China

Received:2022-08-29 Revised:2023-01-06 Online:2023-09-05 Published:2023-09-01
Contact: ^*xiaopinggu@nju.edu.cn

Abstract

Abstract: Objective To investigate the role of NMDAR-cADPR-RyRs signaling pathway in remifentanil-induced hyperalgesia(RIH). Methods The rat model of postoperative hyperalgesia induced by remifentanil was established. SD rats were randomly divided into 6 groups as: control group, model group, RIH group, RIH+saline group, RIH+ketamine group and RIH+8-Br-cADPR group with 6 animals in each. N-methy-D-aspartic acid receptor(NMDA) antagonist ketamine or cyclic ADP-ribose(cADPR) antagonist 8-Br-cADPR was injected intrathecally 30 minutes before surgical operation in group RIH+ketamine and group RIH+8-Br-cADPR respectively. PWMT and PWTL were measured before operation and on the 1st, 2nd and 3rd days after operation. Western blotwas used to detect the protein level of p-NR2B, p-CaMKII, RyR1 and RyR3 in spinal dorsal horn neurons. The concentration of cADPR was measured by enzyme cycling assay. Results Compared with model group, PWMT and PWTL in RIH group decreased significantly on the first and the second day after remifentanil infusion, while p-NR2B, p-CaMKII, RyR1, RyR3 and cADPR in the spinal dorsal horn increased significantly (P＜0.05). After intrathecal injection of ketamine or 8-Br-cADPR, hypersensitivity to mechanical pain and thermal pain was alleviated in RIH+ketamine group and RIH+8-Br-cADPR group, and the expression level of p-NR2B, p-CaMKII, RyR1, RyR3 and cADPR decreased as compared with RIH group (P＜0.05). Conclusions Remifentanil-induced postoperative hyperalgesia of rat is attenuated by blocking NMDAR-cADPR-RyRs signaling pathway.

Key words: remifentanil, hyperalgesia, ketamine, 8-Br-cADPR, ryanodine receptors

CLC Number:

R614

QIAN Yue, WANG Fang, ZHANG Jing, XIA Tianjiao, GU Xiaoping. Remifentanil-induced postoperative hyperalgesia is attenuated by inhibition of NMDAR-cADPR-RyRs signaling pathway in the spinal cord of rats[J]. Basic & Clinical Medicine, 2023, 43(9): 1335-1340.

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Remifentanil-induced postoperative hyperalgesia is attenuated by inhibition of NMDAR-cADPR-RyRs signaling pathway in the spinal cord of rats

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