IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0256870.html
   My bibliography  Save this article

Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway

Author

Listed:
  • Yaqiong Yang
  • Yu Sun
  • Rong Hu
  • Jia Yan
  • Ziheng Wang
  • Wenlong Li
  • Hong Jiang

Abstract

Although they represent the cornerstone of analgesic therapy, opioids, such as morphine, are limited in efficacy by drug tolerance, hyperalgesia and other side effects. Activation of microglia and the consequent production of proinflammatory cytokines play a key pathogenic role in morphine tolerance, but the exact mechanisms are not well understood. This study aimed to investigate the regulatory mechanism of epidermal growth factor receptor (EGFR) on microglial activation induced by morphine in mouse microglial BV-2 cells. In this research, BV-2 cells were stimulated with morphine or pretreated with AG1478 (an inhibitor of EGFR). Expression levels of cluster of differentiation molecule 11b (CD11b), EGFR, and phospho-EGFR were detected by immunofluorescence staining. Cell signaling was assayed by Western blot. The migration ability of BV-2 cells was tested by Transwell assay. The production of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in the cell supernatant was determined by ELISA. We observed that the expression of CD11b induced by morphine was increased in a dose- and time- dependent manner in BV-2 cells. Phosphorylation levels of EGFR and ERK1/2, migration of BV-2 cells, and production of IL-1β and TNFα were markedly enhanced by morphine treatment. The activation, migration, and production of proinflammatory cytokines in BV-2 cells were inhibited by blocking the EGFR signaling pathway with AG1478. The present study demonstrated that the EGFR/ERK signaling pathway may represent a novel pharmacological strategy to suppress morphine tolerance through attenuation of microglial activation.

Suggested Citation

  • Yaqiong Yang & Yu Sun & Rong Hu & Jia Yan & Ziheng Wang & Wenlong Li & Hong Jiang, 2021. "Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway," PLOS ONE, Public Library of Science, vol. 16(9), pages 1-15, September.
    • Handle: RePEc:plo:pone00:0256870
    DOI: 10.1371/journal.pone.0256870
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256870
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0256870&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0256870?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Paul T E Cusack, 2020. "On Pain," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 31(3), pages 24253-24254, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Daniel Niederer & Juliane Mueller, 2020. "Sustainability effects of motor control stabilisation exercises on pain and function in chronic nonspecific low back pain patients: A systematic review with meta-analysis and meta-regression," PLOS ONE, Public Library of Science, vol. 15(1), pages 1-21, January.
    2. Sana Sadiq & Khadija Anasse & Najib Slimani, 2022. "The impact of mobile phones on high school students: connecting the research dots," Technium Social Sciences Journal, Technium Science, vol. 30(1), pages 252-270, April.
    3. Jitka Vseteckova, 2020. "Psychological Therapy for ICT Literate Older Adults in the Time of COVID-19 - Perceptions on the Acceptability of Online Versus Face to Face Versions of a Mindfulness for Later Life Group," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 31(1), pages 23912-23916, October.
    4. Khalid Ahmed Al-Ansari & Ahmet Faruk Aysan, 2021. "More than ten years of Blockchain creation: How did we use the technology and which direction is the research heading? [Plus de dix ans de création Blockchain : Comment avons-nous utilisé la techno," Working Papers hal-03343048, HAL.
    5. Ling, Gabriel Hoh Teck & Suhud, Nur Amiera binti Md & Leng, Pau Chung & Yeo, Lee Bak & Cheng, Chin Tiong & Ahmad, Mohd Hamdan Haji & Matusin, AK Mohd Rafiq AK, 2021. "Factors Influencing Asia-Pacific Countries’ Success Level in Curbing COVID-19: A Review Using a Social–Ecological System (SES) Framework," SocArXiv b9f2w, Center for Open Science.
    6. Benedict E. DeDominicis, 2021. "Multinational Enterprises And Economic Nationalism: A Strategic Analysis Of Culture," Global Journal of Business Research, The Institute for Business and Finance Research, vol. 15(1), pages 19-66.
    7. Robert J. R. Elliott & Ingmar Schumacher & Cees Withagen, 2020. "Suggestions for a Covid-19 Post-Pandemic Research Agenda in Environmental Economics," Environmental & Resource Economics, Springer;European Association of Environmental and Resource Economists, vol. 76(4), pages 1187-1213, August.
    8. Rafał Krupiński, 2020. "Virtual Reality System and Scientific Visualisation for Smart Designing and Evaluating of Lighting," Energies, MDPI, vol. 13(20), pages 1-17, October.
    9. Werner Hölzl & Michael Böheim & Klaus Friesenbichler & Agnes Kügler & Thomas Leoni, 2021. "Staatliche Hilfsmaßnahmen für Unternehmen in der COVID-19-Krise. Eine begleitende Analyse operativer Aspekte und Unternehmenseinschätzungen," WIFO Studies, WIFO, number 66624.
    10. Thorbecke, Willem & Chen, Chen & Salike, Nimesh, 2021. "China’s exports in a protectionist world," Journal of Asian Economics, Elsevier, vol. 77(C).
    11. Óscar Chiva-Bartoll & Honorato Morente-Oria & Francisco Tomás González-Fernández & Pedro Jesús Ruiz-Montero, 2020. "Anxiety and Bodily Pain in Older Women Participants in a Physical Education Program. A Multiple Moderated Mediation Analysis," Sustainability, MDPI, vol. 12(10), pages 1-12, May.
    12. Gigi Foster, 2020. "The behavioural economics of government responses to COVID-19," Journal of Behavioral Economics for Policy, Society for the Advancement of Behavioral Economics (SABE), vol. 4(S3), pages 11-43, December.
    13. Reza Salajegheh & Edward C Nemergut & Terran M Rice & Roy Joseph & Siny Tsang & Bethany M Sarosiek & C Paige Muthusubramanian & Katelyn M Hipwell & Kate B Horton & Bhiken I Naik, 2020. "Impact of a perioperative oral opioid substitution protocol during the nationwide intravenous opioid shortage: A single center, interrupted time series with segmented regression analysis," PLOS ONE, Public Library of Science, vol. 15(6), pages 1-13, June.
    14. Jaroslav Flegr & Radim Kuba & Robin Kopecký, 2020. "Rhesus-minus phenotype as a predictor of sexual desire and behavior, wellbeing, mental health, and fecundity," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-11, July.
    15. Tonata Dengeingei & Laura Uusiku & Olivia N Tuhadeleni & Alice Lifalaza, 2020. "Assessing Knowledge and Practice Regarding the Management of Dysmenorrhea Among Students at University of Namibia Rundu Campus," Global Journal of Health Science, Canadian Center of Science and Education, vol. 12(9), pages 105-105, August.
    16. Craig C Kage & Mohsen Akbari-Shandiz & Mary H Foltz & Rebekah L Lawrence & Taycia L Brandon & Nathaniel E Helwig & Arin M Ellingson, 2020. "Validation of an automated shape-matching algorithm for biplane radiographic spine osteokinematics and radiostereometric analysis error quantification," PLOS ONE, Public Library of Science, vol. 15(2), pages 1-15, February.
    17. Piotr Raźniak & György Csomós & Sławomir Dorocki & Anna Winiarczyk-Raźniak, 2021. "Exploring the Shifting Geographical Pattern of the Global Command-and-Control Function of Cities," Sustainability, MDPI, vol. 13(22), pages 1-15, November.
    18. Felbermayr, Gabriel & Morgan, T. Clifton & Syropoulos, Constantinos & Yotov, Yoto V., 2021. "Understanding economic sanctions: Interdisciplinary perspectives on theory and evidence," European Economic Review, Elsevier, vol. 135(C).
    19. Michael Dolph & Gabriel Tremblay & Hoyee Leong, 2021. "Cost Effectiveness of Triplet Selinexor-Bortezomib-Dexamethasone (XVd) in Previously Treated Multiple Myeloma (MM) Based on Results from the Phase III BOSTON Trial," PharmacoEconomics, Springer, vol. 39(11), pages 1309-1325, November.
    20. Zack Cooper & Joseph J. Doyle Jr. & John A. Graves & Jonathan Gruber, 2022. "Do Higher-Priced Hospitals Deliver Higher-Quality Care?," NBER Working Papers 29809, National Bureau of Economic Research, Inc.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0256870. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.