抑制脊髓NMDAR-cADPR-RyRs信号通路减弱瑞芬太尼诱发的大鼠术后痛觉过敏

doi:10.16352/j.issn.1001-6325.2023.09.1335

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (9): 1335-1340.doi: 10.16352/j.issn.1001-6325.2023.09.1335

• 研究论文 • 下一篇

抑制脊髓NMDAR-cADPR-RyRs信号通路减弱瑞芬太尼诱发的大鼠术后痛觉过敏

钱玥¹, 王芳¹, 张兢¹, 夏天娇², 顾小萍^1*

1.南京医科大学附属鼓楼临床医学院麻醉科,江苏南京 210008;
2.南京大学医学院,江苏南京 210008

收稿日期:2022-08-29 修回日期:2023-01-06 出版日期:2023-09-05 发布日期:2023-09-01
通讯作者: ^*xiaopinggu@nju.edu.cn
基金资助:
国家自然科学基金(81701371,81730033);江苏省自然科学基金(BK20170654)

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

摘要/Abstract

摘要： 目的探讨NMDAR-cADPR-RyRs信号通路在瑞芬太尼诱发的大鼠痛觉过敏中的作用。方法建立瑞芬太尼诱发(术后)痛觉过敏(RIH)大鼠模型。将大鼠按随机数字表法分为6组(n=8):对照组、手术组、痛觉过敏(RIH)组、0.9%氯化钠溶液组、氯胺酮组和环状二磷酸腺苷核糖(cADPR)拮抗剂组。在术前和术后第1、2、3天检测机械缩足阈值(PWMT)和热缩足潜伏期(PWTL)阈值。Western blot检测脊髓背角神经元中p-NR2B、p-CaMKII和RyR1和RyR3的蛋白水平;酶循环法测量cADPR浓度。结果与手术组相比,RIH组在输注瑞芬太尼后第1和第2天PWMT和PWTL显著降低,同时脊髓背角p-NR2B、p-CaMKII、RyR1、RyR3和cADPR水平显著上调(P＜0.05)。鞘内注射氯胺酮或8-Br-cADPR后,与RIH组相比RIH+Ketamin组和RIH+cADPR组的机械痛觉和热痛觉过敏缓解,p-NR2B、p-CaMKII、RyR1、RyR3和cADPR的表达水平下降(P＜0.05)。结论抑制NMDAR-cADPR-RyRs信号通路可缓解瑞芬太尼诱发的大鼠术后痛觉过敏。

关键词: 瑞芬太尼, 痛觉过敏, 氯胺酮, 8-溴-环二磷酸腺苷核糖, 兰尼碱受体

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

中图分类号:

R614

钱玥, 王芳, 张兢, 夏天娇, 顾小萍. 抑制脊髓NMDAR-cADPR-RyRs信号通路减弱瑞芬太尼诱发的大鼠术后痛觉过敏[J]. 基础医学与临床, 2023, 43(9): 1335-1340.

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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参考文献

[1]Kim SH, Stoicea N, Soghomonyan S, et al. Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review[J]. Front Pharmacol, 2014, 5:108.doi:10.3389/fphar.2014-00108.
[2]Meissner G. The structural basis of ryanodine receptor ion channel function[J]. J Gen Physiol, 2017, 149:1065-1089.
[3]Ohashi R, Sakata S, Naito A, et al. Dendritic differentiation of cerebellar Purkinje cells is promoted by ryanodine receptors expressed by Purkinje and granule cells[J]. Dev Neurobiol, 2014, 74:467-480.
[4]Llanos P, Contreras-Ferrat A, Barrientos G, et al. Glucose-dependent insulin secretion in pancreatic beta-cell islets from male rats requires Ca²⁺ release via ROS-stimulated ryanodine receptors[J]. PLoS One, 2015, 10:1-24.
[5]Yu PL, Liu ZM, Yu XF, et al. Direct gating of the TRPM2 channel by cADPR via specific interactions with the ADPR binding pocket[J]. Cell Rep, 2019, 27:3684-3695.
[6]Luiz FF, Eugen VK, Dionéia A, et al. Marked sexual dimorphism in the role of the ryanodine receptor in a model of pain chronification in the Rat[J]. Sci Rep, 2016, 6:1-12.
[7]Lü N, Cheng LZ, Zhang YQ, et al. Involvement of ryanodine receptors in tetanic sciatic stimulation-induced long-term potentiation of spinal dorsal horn and persistent pain in rats[J]. J Neurosci Res, 2012, 90:1096-1104.
[8]Mei XP, Zhang H, Wang W, et al. Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuro-pathic pain[J]. J Neuroinflammation, 2011, 8:6-15.
[9]Peng QY, Wang YM, Chen CX, et al. Inhibiting the CD38/cADPR pathway protected rats against sepsis associated brain injury[J]. Brain Res, 2018, 1678:56-63.
[10]Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain[J]. Pain, 1996, 64:493-501.
[11]Jiang M, Zhang W, Cheng CX, et al. Intrathecal injection of KN93 attenuates paradoxical remifentanil-induced postoperative hyperalgesia by inhibiting spinal CaMKII phosphorylation in rats[J]. Pharmacol Biochem Behav, 2015, 134:35-41.
[12]Crown ED, Gwak Y, Ye Z, et a1. Calcium/calmodulin-dependent kinase II contributes to persistent central neuropathic pain following spinal cord injury[J]. Pain, 2012, 153: 710-721.
[13]Faas GC,Raghavachari S,Lisman JE, et al. Calmodulin as a direct detector of Ca²⁺ signals[J]. Nat Neurosci, 2011, 14: 301-304.
[14]Cheong E, Kim C, Choi BJ, et al. Thalamic ryanodine receptors are involved in controlling the tonic firing of thalamocortical neurons and inflammatory pain signal processing[J]. J Neurosci, 2011, 31:1213-1218.

抑制脊髓NMDAR-cADPR-RyRs信号通路减弱瑞芬太尼诱发的大鼠术后痛觉过敏

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

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