Ivabradine Prevents Remifentanil Induced Hyperalgesia in Mice
[Objective]To investigate the effect of ivabradine,an inhibitor of peripheral HCN channel,on remifentanil-induced hyperalgesia in mice.[Methods]The 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.[Results]Compared 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).[Conclusions]Ivabradine 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.
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维普
