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      Is Open Access

      Investigation of Neuroprotective Effects of Erythropoietin on Chronic Neuropathic Pain in a Chronic Constriction Injury Rat Model

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          Abstract

          Introduction

          Neuropathic pain is pretty common in modern society, and the treatment effect is far from satisfactory. This study aimed to find evidence of the neuroprotective effect of erythropoietin (EPO) in the treatment of neuropathic pain in a rat model of chronic constriction injury (CCI).

          Methods

          A total of 30 rats were randomly divided into sham operation group, CCI group, or CCI+EPO group. The mechanical and thermal nociception thresholds are evaluated as behavioral assessments. The dorsal root ganglion cells were morphologically evaluated by hematoxylin and eosin staining, and AMPK, p-AMPK, mTOR, p70S6K, and AQP-2 proteins were compared and analyzed by Western blotting. Compared with the sham operation group, rats in the CCI group had shorter paw withdrawal threshold and paw withdrawal latency, abnormal morphology, and increased satellite glial cells.

          Results

          After treatment with EPO, these changes were significantly reversed. In vivo administration of erythropoietin seems to be able to regulate the expression of AQP-2 through the AMPK/mTOR/p70S6K pathway. Our study provides behavioral, morphological, and immunoblot evidence to prove the neuroprotective effect of EPO in the treatment of chronic neuropathic pain in the CCI rat model.

          Conclusion

          Our results indicate that EPO has the potential to treat neuropathic pain caused by peripheral nerve injury, although further verification is needed.

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          Most cited references 39

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          A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man

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            AMPK: guardian of metabolism and mitochondrial homeostasis.

            Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.
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              The dorsal root ganglion in chronic pain and as a target for neuromodulation: a review.

               Elliot Krames (2015)
              In the not-too-distant past, the dorsal root ganglion (DRG) was portrayed as a passive neural structure without involvement in the development or maintenance of chronic neuropathic pain (NP). The DRG was thought of as a structure that merely "supported" physiologic communication between the peripheral nervous system (PNS) and the central nervous system (CNS). Newer scientific information regarding the anatomic and physiologic changes that occur within the DRG as a result of environmental pressures has dispelled this concept and suggests that the DRG is an active participant in the development of NP. This new information, along with new clinical data showing that stimulation of the DRG reduces intensity of pain, suggests that the DRG can be a robust target for neuromodulation therapies.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                30 November 2020
                2020
                : 13
                : 3147-3155
                Affiliations
                [1 ]Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan 450052, People’s Republic of China
                Author notes
                Correspondence: Zhaohui Lou Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan450052, People’s Republic of ChinaTel/Fax +86-371-6796611 Email zhaohuilou123@163.com
                Article
                285870
                10.2147/JPR.S285870
                7725095
                © 2020 Zhang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 3, References: 39, Pages: 9
                Funding
                Funded by: the Henan Provincial Medical Science and Technology Research Project;
                This research was funded by the Henan Provincial Medical Science and Technology Research Project (No. SBGJ2018030).
                Categories
                Original Research

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