Role of Kv7.2 in dorsal root ganglion in reduction of paclitaxel-induced neuropathic pain by morphine in rats
10.3760/cma.j.cn131073.20231231.00612
- VernacularTitle:背根神经节Kv7.2在吗啡减轻紫杉醇诱发大鼠神经病理性痛中的作用
- Author:
Ying ZHOU
1
;
Mengxia YAO
;
Ying WANG
;
Huizhe ZHENG
;
Meixiang ZHAN
Author Information
1. 福建医科大学肿瘤临床医学院 福建省肿瘤医院麻醉科，福州 350000
- Keywords:
Potassium channels, voltage-gated;
Ganglia, spinal;
Morphine;
Taxol;
Neuralgia
- From:
Chinese Journal of Anesthesiology
2024;44(6):705-709
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of Kv7.2 in the dorsal root ganglion (DRG) in reduction of paclitaxel-induced neuropathic pain (NPP) by morphine in rats.Methods:SPF healthy male Sprague-Dawley rats, aged 5 weeks, weighing 140-160 g, were randomly selected. This experiment was performed in two parts. Experiment Ⅰ Seventy-two rats were divided into control group (group C), control + morphine group (group C+ M), NPP-1 group (group NPP1) and NPP-1 + morphine group (group NPP1+ M), with 18 animals in each group. Experiment Ⅱ Twenty-four rats were divided into NPP2 group, NPP2+ ML252 group, NPP2+ morphine group (NPP2+ M group), and NPP2 + morphine + ML252 group (NPP2+ M+ ML252 group), with 6 animals in each group. The model of NPP was developed by intraperitoneal injection of paclitaxel 2 mg/kg, once every 2 days for 4 times. After preparation of the model, morphine 5 mg/kg was subcutaneously injected in C+ M group, NPP1+ M group, NPP2+ M group and NPP2+ M+ ML252 group, and potassium channel inhibitor ML252 10 mg/kg was intraperitoneally injected for 7 consecutive days in NPP2+ ML252 group and NPP2+ M+ ML252 group. Six rats were randomly selected from each group on the 1st, 3rd and 7th days after the end of continuous administration in experiment Ⅰ and from each group on the 7th day after the end of continuous administration in experiment Ⅱ for measurement of the mechanical paw withdrawal threshold (MWT) and cold paw withdrawal latency (CWL). At the end of the behavioral assessment, the rats were sacrificed and the DRG was removed for determination of Kv7.2 expression by Western blot. On the 1st day after the end of continuous administration in experiment Ⅰ, the expression of Kv7.2 mRNA in DRG was detected using quantitative real-time polymerase chain reaction, and immunofluorescence was used to detect the co-expression of Kv7.2 with neurons and glial cells in group C.Results:Experiment Ⅰ Compared with C group, the MWT was significantly increased, the expression of Kv7.2 protein and mRNA was up-regulated at each time point ( P<0.05), and no significant change was found in the CWL in C+ M group ( P>0.05), and the MWT was significantly decreased, the CWL was shortened, and the expression of Kv7.2 protein and mRNA was down-regulated at each time point in NPP1 group ( P<0.05). Compared with NPP1 group, the MWT was significantly increased, the CWL was prolonged, and the expression of Kv7.2 protein and mRNA was up-regulated at each time point in NPP1+ M group ( P<0.05). Kv7.2 in DRG was expressed in peptideergic small and medium diameter neurons, non-peptideergic small and medium diameter neurons and large diameter neurons, but not in glial cells. Experiment Ⅱ Compared with NPP2 group, no significant change was found in the expression of MWT, CWL and Kv7.2 in NPP2+ ML252 group ( P>0.05), and the MWT was significantly increased, CWL was prolonged, and the expression of Kv7.2 in DRG was up-regulated in NPP2+ M group ( P<0.05). Compared with NPP2+ M group, the MWT was significantly decreased, CWL was shortened, and the expression of Kv7.2 in DRG was down-regulated in NPP2+ M+ ML252 group ( P<0.05). Conclusions:Down-regulation of Kv7.2 expression in DRG is involved in the reduction of paclitaxel-induced NPP by morphine in rats.
