Opioid infusions at different times of the day produce varying degrees of opioid-induced hyperalgesia

作者全名："Shu, Bin; Liu, Huiting; Zheng, Xuemei; He, Jianrong; Wu, Yingcai; Chen, Jie; Chen, Yuanjing; Tian, Hongni; Ju, Dapeng; Huang, He; Duan, Guangyou"

作者地址："[Shu, Bin; Liu, Huiting; Zheng, Xuemei; He, Jianrong; Wu, Yingcai; Chen, Jie; Chen, Yuanjing; Tian, Hongni; Ju, Dapeng; Huang, He; Duan, Guangyou] Chongqing Med Univ, Affiliated Hosp 2, Dept Anaesthesiol, Chongqing, Peoples R China; [Liu, Huiting] Chongqing Med Univ, Affiliated Hosp 3, Dept Anaesthesiol, Chongqing, Peoples R China"

通信作者："Duan, GY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Anaesthesiol, Chongqing, Peoples R China."

来源：BRITISH JOURNAL OF ANAESTHESIA

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001112343800001

JCR分区：Q1

影响因子：9.1

年份：2023

卷号：131

期号：6

开始页：1072

结束页：1081

文献类型：Article; Early Access

关键词：circadian rhythm; cytochrome P450 enzyme; nonspecific esterase; opioid-induced hyperalgesia; remifentanil; sufentanil

摘要："Background:<bold> </bold>Opioids are metabolised by enzymes the activities of which vary with the circadian rhythm. We examined whether opioid infusions administered at different times of the day produce varying degrees of opioid-induced hyperalgesia (OIH) in animal experiments and clinical studies.Methods:<bold> </bold>Male Sprague-Dawley rats received remifentanil infusions (1 mu g kg(-1)<middle dot>min(-1) for 1 h) at Zeitgeber times (ZT) 0, 4, 8, 12, 16, or 20 h. Rhythmicity of mechanical hypersensitivity was assayed after the infusion. Mechanical hypersensitivity, drug concentration, and metabolic enzyme activity of Wistar rats that received sufentanil (10 mu g kg(-1); four consecutive i.p. injections at 15-min intervals) or remifentanil infusion at ZT0 or ZT8 were assayed. Sixty patients who underwent abdominal laparoscopic surgery under general anaesthesia received remifentanil infusion (0.15 mu g kg(-1) min(-1)) and sufentanil injection (0.2 mu g kg(-1)) at induction and skin incision, respectively. Postoperative pressure pain sensitivity, pain Numeric Rating Scale (NRS), drug concentrations, and nonspecific esterase activity were assessed.Results:<bold> </bold>Sprague-Dawley rats that received remifentanil infusion exhibited a robust rhythmic paw withdrawal threshold (JTK_CYCLE: P=0.001, Q=0.001, Phase=26). Wistar rats infused with remifentanil or sufentanil at ZT8 exhibited greater OIH (P<0.001) than those infused at ZT0, with higher blood concentrations (P<0.001) and lower metabolic enzyme activities (P=0.026 and P=0.028, respectively). Patients in the afternoon group exhibited higher pressure pain sensitivity at forearm (P=0.002), higher NRS (P<0.05), higher drug concentrations (sufentanil: P=0.037, remifentanil: P=0.005), and lower nonspecific esterase activity (P=0.024) than the morning group.Conclusions:<bold> </bold>Opioid infusions administered at different times of day produced varying degrees of OIH, possibly related to circadian rhythms of metabolic enzyme activities."

基金机构："National Natural Science Foundation of China [82171210]; Chongqing Natural Science Foundation [CSTC2021JCYJ- MSXMX0188, CSTB2022NSCQ-BHX0015]"

基金资助正文：Funding National Natural Science Foundation of China (82171210) ; Chongqing Natural Science Foundation (CSTC2021JCYJ- MSXMX0188 and CSTB2022NSCQ-BHX0015) .