ArticlePloS one2021
Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- GPNMB regulates EGFR mitochondrial translocation via HK2, influencing microglial respiratory chain and metabolic defects to promote polarization and stroke progression.Cell biology and toxicology · 2026Article
- EGFR activation sensitizes trigeminal NMDA receptors to promote pain and morphine analgesic tolerance in oral cancer.Science signaling · 2026Article
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- Regulation of glial markers expression in the rat basolateral amygdala and hippocampus during morphine aversive memory retrieval and its extinction.Behavioral and brain functions : BBF · 2025Article
- Opioid-induced immunosuppression of brain myeloid cells in SIV-infected rhesus macaques.Research square · 2025Article
- Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses.Frontiers in immunology · 2025Article
- Study of the Chemical Composition and Anti-Inflammatory Mechanism of Shiyiwei Golden Pill Based on UPLC-Q-TOF/MS and Network Pharmacology.Drug design, development and therapy · 2025Article
- The Melatonin Type 2 Receptor Agonist IIK7 Attenuates and Reverses Morphine Tolerance in Neuropathic Pain Rats Through the Suppression of Neuroinflammation in the Spinal Cord.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights.Microbial biotechnology · 2024Review
- Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain.Cell communication and signaling : CCS · 2024Article
- CASK Mediates Oxidative Stress-Induced Microglial Apoptosis-Inducing Factor-Independent Parthanatos Cell Death via Promoting PARP-1 Hyperactivation and Mitochondrial Dysfunction.Antioxidants (Basel, Switzerland) · 2024Article
- Receptors on Microglia.Advances in neurobiology · 2024Review
- Fentanyl enhances immune cell response through TLR4/MD-2 complex.Frontiers in pharmacology · 2024Article
- Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- Single-cell profiling of glial cells from the mouse amygdala under opioid dependent and withdrawal states.iScience · 2023Article
- Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Microglial inflammation modulates opioid analgesic tolerance.Journal of neuroscience research · 2023Review
- Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders.Biomolecules · 2023Review
- Inhibiting EGFR/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A.Frontiers in immunology · 2022Article
- Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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