Ivabradine Prevents Remifentanil Induced Hyperalgesia in Mice
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240907.010
- VernacularTitle:伊伐布雷定抑制瑞芬太尼诱导的小鼠痛觉过敏
- Author:
Li XIAO
1
;
Xiaoe WANG
1
;
Wenqi HUANG
1
;
Yu CUI
2
Author Information
1. Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
2. Department of Physiology, Sun Yat-sen University School of Medicine, Shenzhen 518107, China
- Publication Type:Journal Article
- Keywords:
remifentanil;
hyperalgesia;
ivabradine;
mice;
c-Fos;
hyperpolarization activated cyclic nucleotide gated
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2024;45(5):694-700
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of ivabradine， an inhibitor of peripheral HCN channel， on remifentanil-induced hyperalgesia in mice. MethodsThe model of remifentanil-induced hyperalgesia was established by intravenously infusing remifentanil 2 μg/（kg·min） for 1 h through tail vein of adult male C57/BL6 mice. To observe the effect of ivabradine on remifentanil induced hyperalgesia， ivabradine （5 mg/kg） was injected subcutaneously 30 minutes before remifentanil infusion. Forty mice were equally and randomly divided into 4 groups： saline group， remifentanil group， remifentanil + vehicle group and remifentanil + ivabradine group. In each group， six mice were used to test mechanical and thermal pain thresholds at 24 h before （baseline） and on 1 d， 3 d， 5 d after remifentanil or saline infusion. Four mice of each group were used to detected c-Fos positive cell in spinal dorsal horn by immunofluorescence on 1 d after remifentanil or saline infusion. ResultsCompared with the saline group， a significant decrease in mechanical or thermal threshold was observed on 1 d and 3 d after remifentanil infusion （P<0.001）， and the number of c-Fos positive neurons in the lumbar dorsal horn increased significantly （P<0.001）. Compared with vehicle group， subcutaneous injection of ivabradine effectively inhibited remifentanil induced hyperalgesia （P<0.001） and blocked the increase of c-Fos positive neurons in the lumbar dorsal horn on 1 d following remifentanil treatment （P<0.001）. ConclusionsIvabradine could effectively prevent remifentanil-induced hyperalgesia in mice. The possible mechanism underlying this effect is that ivabradine suppresses the enhanced peripheral nociceptive input onto spinal cord neurons.
