scholarly journals Beneficial Effects of Electroacupuncture on Neuropathic Pain Evoked by Spinal Cord Injury and Involvement of PI3K-mTOR Mechanisms

2018 ◽  
Vol 21 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Yujie Wang ◽  
Yu Zhao ◽  
Xiaohui Ma ◽  
Jing Li ◽  
Junling Hou ◽  
...  

The purpose of this study was to examine the beneficial effects of electroacupuncture (EA) on neuropathic pain evoked by spinal cord injury (SCI) and determine the underlying molecular mechanisms of these effects. SCI was induced in rats. Behavioral tests were performed to examine pain responses induced by mechanical and thermal stimulation. Western blot analysis was used to measure the protein expression of phosphorylated mammalian target of rapamycin (p-mTOR), mTOR-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p-S6K1), and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1) in the superficial dorsal horn of the spinal cord. We showed that SCI increased the expression of p-mTOR, p-S6K1, and p-4E-BP1. The EA intervention attenuated the upregulation of mTOR signaling and alleviated mechanical and thermal pain responses in SCI rats. Blocking spinal mTOR by intrathecal injection of rapamycin also inhibited mechanical and thermal pain. In addition, blocking spinal phosphorylated phosphatidylinositide 3-kinase (p-PI3K) pathway attenuated p-mTOR pathways and mechanical and thermal hyperalgesia in SCI rats. EA also decreased the enhanced p-PI3K in the superficial dorsal horn of SCI rats. In conclusion, findings revealed specific signaling pathways that lead to neuropathic pain in response to SCI, including activation of PI3K-mTOR signaling. Further, results link the beneficial role of EA in alleviating SCI-induced neuropathic pain to its effect on these molecular mechanisms.

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jingying Zhou ◽  
Xue Huo ◽  
Benson O. A. Botchway ◽  
Luyao Xu ◽  
Xiaofang Meng ◽  
...  

Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway. Herein, we explicate the role of resveratrol in the repair of SCI through the inhibition of the mTOR signaling pathway. The inhibition of the mTOR pathway by resveratrol has the potential of serving as a neuronal restorative mechanism following SCI.


2017 ◽  
Vol 13 ◽  
pp. 174480691668801 ◽  
Author(s):  
Xiaoyu C Cao ◽  
Laura W Pappalardo ◽  
Stephen G Waxman ◽  
Andrew M Tan

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaoping Wang ◽  
Xiaojia Li ◽  
Bin Huang ◽  
Shuai Ma

AbstractSpinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.


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