Relationship between S-nitrosylation of spinal divalent metal transporter 1 modification and mechanism of remifentanil-induced hyperalgesia in rats
10.3760/cma.j.cn131073.20230521.01115
- VernacularTitle:脊髓DMT1亚硝基化修饰与瑞芬太尼诱发大鼠痛觉过敏机制的关系
- Author:
Ruichen SHU
1
;
Yuan LI
;
Zengli ZHANG
;
Kaiyuan WANG
;
Guolin WANG
;
Yiqing YIN
Author Information
1. 天津医科大学肿瘤医院麻醉科 国家恶性肿瘤临床医学研究中心 天津市恶性肿瘤临床医学研究中心 天津市肿瘤防治重点实验室，天津 300060
- Keywords:
Remifentanil;
Hyperalgesia;
Ion transport;
Nitroso compounds
- From:
Chinese Journal of Anesthesiology
2023;43(11):1355-1359
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship between S-nitrosylation of spinal divalent metal transporter 1 (DMT1) modification and mechanism of remifentanil-induced hyperalgesia in rats.Methods:Forty pathogen-free healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), L-NAME group (group C+ L) and remifentanil+ L-NAME group (group R+ L). Normal saline was infused at a rate of 0.1 ml·kg -1·min -1 for 60 min via the caudal vein in C group. Remifentanil was infused at a rate of 1.0 μg·kg -1·min -1 for 60 min via the caudal vein in R group. L-NAME 30 mg/kg was intraperitoneally injected, and 10 min later normal saline was infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C+ L group. L-NAME 30 mg/kg was intraperitoneally injected, and 10 min later remifentanil was infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R+ L group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before iv infusion and 6, 24 and 48 h after the end of infusion (T 0-3). All the rats were sacrificed under anesthesia after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of neuronal nitric oxide sythases (nNOS) and DMT1 mRNA (using quantitative real-time polymerase chain reaction), extraction of nitrosylated proteins (by biotin switch assay), expression of nNOS, total DMT1 and S-nitrosylation of DMT1 (by Western blot), nitric oxide (NO) content (by spectrophotometry) and iron content (using atomic absorption spectrophotometer). Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3 in group R ( P<0.05), and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was significantly up-regulated, and contents of NO and iron were increased in R and R+ L groups ( P<0.05), and no significant change was found in each index in group C+ L ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was down-regulated, and contents of NO and iron were decreased in group R+ L ( P<0.05). Compared with group C+ L, the MWT was significantly decreased, and the TWL was shortened at T 1-3, and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was up-regulated, and the contents of NO and iron were increased in group R+ L ( P<0.05). There were no significant differences in the expression of DMT1 mRNA and total DMT1 in spinal cord among all the groups ( P>0.05). Conclusions:Activation of nNOS induces an increase in NO generation in the spinal cord and mediates the S-nitrosylation of DMT1, which may be related to the mechanism of remifentanil-induced hyperalgesia in rats.
