4
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      S100A4 in Spinal Substantia Gelatinosa from Dorsal Root Ganglia Modulates Neuropathic Pain in a Rodent Spinal Nerve Injury Model

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          To detect the spatio-temporal expression of S100A4 in a spinal nerve ligation (SNL) rat model. Also to figure out which other molecules directly interact with S100A4 to explore the possible mechanisms which might be involved in neuropathic pain.

          Methods

          Seven-week-old male SD rats were used for the SNL model construction. Immunofluorescence and Western blotting were used to detect the spatio-temporal expression of S100A4 in the model. S100A4 was co-labeled with a number of related molecules and marker molecules that can distinguish between cell types. After intrathecal injection of S100A4 neutralizing antibody, the behavioral changes of SNL rats were recorded, and molecular changes compared. The direct interaction between S100A4 and other related molecules was verified by co-immunoprecipitation (co-IP) to explore its possible mechanism.

          Results

          After spinal nerve ligation, the content of S100A4 in the dorsal root ganglion (DRG) and spinal dorsal horn increased significantly. Intrathecal injection of S100A4 neutralizing antibody could effectively relieve the mechanical pain in rats. co-IP revealed a direct interaction between S100A4 and RAGE.

          Conclusion

          The content of S100A4 in the DRG and spinal dorsal horn of SNL rats increased, compared with that of the control group. Intrathecal injection of S100A4 neutralizing antibody could effectively relieve the mechanical pain in SNL rats. S100A4 may be involved in the production of neuropathic pain through RAGE or other ways, but the specific mechanism needs to be further studied.

          Related collections

          Most cited references 42

          • Record: found
          • Abstract: found
          • Article: not found

          Calcium-dependent and -independent interactions of the S100 protein family.

          The S100 proteins comprise at least 25 members, forming the largest group of EF-hand signalling proteins in humans. Although the proteins are expressed in many tissues, each S100 protein has generally been shown to have a preference for expression in one particular tissue or cell type. Three-dimensional structures of several S100 family members have shown that the proteins assume a dimeric structure consisting of two EF-hand motifs per monomer. Calcium binding to these S100 proteins, with the exception of S100A10, results in an approx. 40 degrees alteration in the position of helix III, exposing a broad hydrophobic surface that enables the S100 proteins to interact with a variety of target proteins. More than 90 potential target proteins have been documented for the S100 proteins, including the cytoskeletal proteins tubulin, glial fibrillary acidic protein and F-actin, which have been identified mostly from in vitro experiments. In the last 5 years, efforts have concentrated on quantifying the protein interactions of the S100 proteins, identifying in vivo protein partners and understanding the molecular specificity for target protein interactions. Furthermore, the S100 proteins are the only EF-hand proteins that are known to form both homo- and hetero-dimers, and efforts are underway to determine the stabilities of these complexes and structural rationales for their formation and potential differences in their biological roles. This review highlights both the calcium-dependent and -independent interactions of the S100 proteins, with a focus on the structures of the complexes, differences and similarities in the strengths of the interactions, and preferences for homo- compared with hetero-dimeric S100 protein assembly.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain

              The previous decade has seen a rapid increase in microglial studies on pain, with a unique focus on microgliosis in the spinal cord after nerve injury and neuropathic pain. Numerous signaling molecules are altered in microglia and contribute to the pathogenesis of pain. Here we discuss how microglial signaling regulates spinal cord synaptic plasticity in acute and chronic pain conditions with different degrees and variations of microgliosis. We highlight that microglial mediators such as pro- and anti-inflammatory cytokines are powerful neuromodulators that regulate synaptic transmission and pain via neuron-glial interactions. We also reveal an emerging role of microglia in the resolution of pain, in part via specialized pro-resolving mediators including resolvins, protectins and maresins. We also discuss a possible role of microglia in chronic itch.
                Bookmark

                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                10 March 2021
                2021
                : 14
                : 665-679
                Affiliations
                [1 ]Department of Anesthesiology, Changzheng Hospital, Naval Medical University , Shanghai, People’s Republic of China
                [2 ]Department of General Surgery, Affiliated Xinchang Hospital of Shaoxing University , Zhejiang, People’s Republic of China
                [3 ]Department of Neurobiology, Key Laboratory of Molecular Neurobiology, Ministry of Education, Naval Medical University , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Zhenghua Xiang Department of Neurobiology, Key Laboratory of Molecular Neurobiology, Ministry of Education, Naval Medical University , No. 800 Xiangyin Road, Shanghai, 200433, People’s Republic of ChinaTel +86 21 81871044Fax +86 21 81885822 Email xiang-zhenghua@163.com
                Jun Qian Department of General Surgery, Affiliated Xinchang Hospital of Shaoxing University , No. 117 Middle Gushan Road, Xinchang, Zhejiang, 312500, People’s Republic of ChinaTel +86 575 8638079 Email qianj001@163.com
                [*]

                These authors contributed equally to this work

                Article
                293462
                10.2147/JPR.S293462
                7956897
                © 2021 Jiang 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, Tables: 1, References: 42, Pages: 15
                Categories
                Original Research

                Comments

                Comment on this article