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      Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model

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          Abstract

          Background

          Neuropathic pain seriously affects life quality, and it is urgent to develop novel drugs with high efficacy and few side effects. Sanguinarine (SG) is a natural plant medicine with anti-inflammatory and neuroprotection effects. This study aimed to investigate the effect of SG on chronic constriction injury (CCI)-induced neuropathic pain.

          Materials and Methods

          CCI rat model was established and rats were randomly divided into sham group, sham + SG group (6.25 mg/kg), CCI group, CCI + SG group (1.00, 2.50 and 6.25 mg/kg). The mechanical sensitivity and heat hypersensitivity of rats were monitored at different time points. Immunohistochemical, PCR, Western blot and ELISA were used to analyze p-p38 MAPK, NF-κB p65, TNF-α, IL-1β, and IL-6 levels.

          Results

          The mechanical sensitivity and heat hypersensitivity significantly reduced in rats of CCI group, but significantly increased in rats of CCI+SG group. TNF-α, IL-1β, and IL-6 levels significantly increased in the spinal cord of CCI rats, but significantly decreased in rats of CCI+SG group. In addition, p38 MAPK activator antagonized beneficial effects of SG on neuropathic pain. Overexpression of p38 MAPK reduced the mechanical sensitivity and heat hypersensitivity, and enhanced NF-κB activity and the expression of inflammatory factors in CCI rats.

          Conclusion

          SG alleviates neuropathic pain via suppressing p38MAPK signaling and downregulating the expression of TNF-α, IL-1β, IL-6 and NF-κB activation. SG may be a potential therapeutic agent to treat neuropathic pain.

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          Most cited references 18

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          The role of the immune system in the generation of neuropathic pain.

          Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems--whether traumatic, metabolic, or toxic--result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                04 November 2020
                2020
                : 14
                : 4725-4733
                Affiliations
                [1 ]Department of Pain Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan, Shandong, People’s Republic of China
                [2 ]Department of Pain Medicine, Taian City Central Hospital , Tai’an, Shandong, People’s Republic of China
                [3 ]Department of Physical Medicine and Rehabilitation, Taian City Central Hospital , Tai’an, Shandong, People’s Republic of China
                [4 ]Department of Orthopaedic Surgery, Taian City Central Hospital , Tai’an, Shandong, People’s Republic of China
                [5 ]Department of Pain Medicine, Qilu Hospital of Shandong University , Jinan, Shandong, People's Republic of China
                Author notes
                Correspondence: Li-Shuang Liang Department of Pain Medicine, Qilu Hospital of Shandong University , 44 Wenhua West Road, Jinan, Shandong Province250012, People’s Republic of ChinaTel/Fax +86 13561764131 Email liangls1224@163.com
                Kai-Gang Zhang Department of Orthopaedic Surgery, Taian City Central Hospital , No. 29 Long Tan Road, Taian, Shandong271000, People’s Republic of ChinaTel/Fax +86 15264832232 Email zhangkg0308@yeah.net
                [*]

                These authors contributed equally to this work

                Article
                276424
                10.2147/DDDT.S276424
                7649226
                © 2020 Yu 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: 8, References: 18, Pages: 9
                Funding
                Funded by: Natural Foundation of Shandong Province;
                Funded by: Taian Science and Technology Guidance Project;
                This work was supported by the Natural Foundation of Shandong Province (no. ZR2017PH010) and Taian Science and Technology Guidance Project (no. 2017NS0143).
                Categories
                Original Research

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