Intrathecal administration with roscovitine attenuates bone cancer pain and inhibits the expression of NMDA receptor 2B subunit in mice

2011 ◽  
Vol 28 ◽  
pp. 199
Author(s):  
Z. Ma ◽  
R. Zhang ◽  
F. Mei ◽  
J. Zhang ◽  
Y. Zheng ◽  
...  
2020 ◽  
Vol 132 (2) ◽  
pp. 357-372 ◽  
Author(s):  
Yanting Mao ◽  
Chenchen Wang ◽  
Xinyu Tian ◽  
Yulin Huang ◽  
Ying Zhang ◽  
...  

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development. Methods The authors used a male mouse model of bone cancer pain. The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414. The nociceptive behaviors, endoplasmic reticulum stress markers, and inflammatory mediators were assessed. Results Increased expression of the p-RNA-dependent protein kinase-like endoplasmic reticulum kinase and p-eukaryotic initiation factor 2α were found in the spinal neurons during bone cancer pain, along with upregulation of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6). Intrathecal administration of TNF-α or lipopolysaccharide increased the expression of endoplasmic reticulum stress markers in control mice. Inhibition of endoplasmic reticulum stress by intrathecal administration of 4-PBA (baseline vs. 3 h: 0.34 ± 0.16 g vs. 1.65 ± 0.40 g in paw withdrawal mechanical threshold, 8.00 ± 1.20 times per 2 min vs. 0.88 ± 0.64 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) or GSK2606414 (baseline vs. 3 h: 0.37 ± 0.08 g vs. 1.38 ± 0.11 g in paw withdrawal mechanical threshold, 8.00 ± 0.93 times per 2 min vs. 3.25 ± 1.04 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) showed time- and dose-dependent antinociception. Meanwhile, decreased expression of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6), as well as decreased activation of astrocytes in the spinal cord, were found after 4-PBA or GSK2606414 treatment. Conclusions Inhibition of inflammatory mediator–triggered endoplasmic reticulum stress in spinal neurons attenuates bone cancer pain via modulation of neuroinflammation, which suggests new approaches to pain relief.


2020 ◽  
Vol 715 ◽  
pp. 134623
Author(s):  
Chengwei Yang ◽  
Xiang Huang ◽  
Sheng Wang ◽  
Mingming Han ◽  
Fang Kang ◽  
...  

Neuroscience ◽  
2008 ◽  
Vol 154 (4) ◽  
pp. 1533-1538 ◽  
Author(s):  
R.-X. Zhang ◽  
B. Liu ◽  
A. Li ◽  
L. Wang ◽  
K. Ren ◽  
...  

2010 ◽  
Vol 1335 ◽  
pp. 83-90 ◽  
Author(s):  
Gu Xiaoping ◽  
Zhou XiaoFang ◽  
Zheng YaGuo ◽  
Zhang Juan ◽  
Wang JunHua ◽  
...  

2020 ◽  
Vol 151 ◽  
pp. 106479
Author(s):  
Iryna A. Khasabova ◽  
Mikhail Y. Golovko ◽  
Svetlana A. Golovko ◽  
Donald A. Simone ◽  
Sergey G. Khasabov

Sign in / Sign up

Export Citation Format

Share Document