Glucocorticoid receptor inhibit the activity of NF-κB through p38 signaling pathway in spinal cord in the spared nerve injury rats

Life Sciences ◽  
2018 ◽  
Vol 208 ◽  
pp. 268-275 ◽  
Author(s):  
Jinping Shao ◽  
Ruiyan Xu ◽  
Ming Li ◽  
Qingzan Zhao ◽  
Xiuhua Ren ◽  
...  
2020 ◽  
Vol 21 (18) ◽  
pp. 6524
Author(s):  
Meng Xue ◽  
Ya-Lan Sun ◽  
Yang-Yang Xia ◽  
Zhi-Hua Huang ◽  
Cheng Huang ◽  
...  

Neuropathic pain is more complex and severely affects the quality of patients’ life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.


2019 ◽  
Vol Volume 12 ◽  
pp. 2851-2863 ◽  
Author(s):  
Yang-yang Xia ◽  
Meng Xue ◽  
Ying Wang ◽  
Zhi-hua Huang ◽  
Cheng Huang

2017 ◽  
Vol 31 (6) ◽  
pp. 494 ◽  
Author(s):  
Park Eun-sung ◽  
Ahn Jung-mo ◽  
Jeon Sang-min ◽  
Cho Hee-jung ◽  
Chung Ki-myung ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260887
Author(s):  
Wei-Hung Chan ◽  
Nian-Cih Huang ◽  
Yi-Wen Lin ◽  
Feng-Yen Lin ◽  
Chien-Sung Tsai ◽  
...  

Previous studies have shown an increase of insulin-like growth factor-2 (IGF2) in animal models of neuropathic pain. We aimed to examine the hypothesis that reducing the expression of IGF2 using intrathecal IGF2 small-interfering RNA (siRNA) would attenuate the development of neuropathic pain in rats after spared nerve injury (SNI). Male Wistar rats were divided into three groups: sham-operated group, in which surgery was performed to cut the muscles without injuring the nerves; SNI group, in which SNI surgery was performed to sever the nerves; and SNI + siRNA IGF2 group, in which SNI surgery was performed, and IGF2-siRNA was administered intrathecally 1 day after SNI. The rats were assessed for mechanical allodynia and cold allodynia 1 day before surgery (baseline), and at 2, 4, 6, 8, and 10 days after siRNA treatment. The rat spinal cord was collected for quantitative polymerase chain reaction and western blot analysis. Compared with the SNI group, rats that received IGF2 siRNA showed a significantly increased SNI-induced paw-withdrawal threshold to metal filament stimulation from Day 4 to Day 10 after SNI surgery. IGF2 siRNA significantly decreased the response duration from the acetone test from Day 2 to Day 10 following SNI surgery. SNI increased IGF2 mRNA expression on Day 2 and increased IGF2 protein expression on Day 8 and Day 10 in the spinal cord of the SNI rats. However, the above-mentioned effects of IGF2 mRNA and protein expression were significantly inhibited in the SNI + IGF2 siRNA group. We demonstrated that intrathecal administration of IGF2 siRNA provided significant inhibition of SNI-induced neuropathic pain via inhibition of IGF2 expression in the spinal cord. The analgesic effect lasted for 10 days. Further exploration of intrathecal IGF2 siRNA administration as a potential therapeutic strategy for neuropathic pain is warranted.


2017 ◽  
Vol Volume 10 ◽  
pp. 2503-2514 ◽  
Author(s):  
Zihao Liu ◽  
Ying Liang ◽  
Honghua Wang ◽  
Zhenhe Lu ◽  
Jinsheng Chen ◽  
...  

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