ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
Interleukin-4 Induces the Release of Opioid Peptides from M1 Macrophages in Pathological Pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
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- Two-sample Mendelian randomization study of gut microbiota and inflammatory proteins: Predictive, preventive, and personalized treatment for migraine.Neural regeneration research · 2026Article
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- Opioids regulate the functional state of immune cells and reduce inflammatory cardiac injury: Role of opioid receptors, MRGPRX2, and TLR4.Journal of biomedical research · 2026Article
- Clinical Factors and Serum Biomarkers Associated With Major Depressive Disorder in Adolescents With and Without Nonsuicidal Self-Injury: A Comparative Cross-Sectional Study.Alpha psychiatry · 2026Article
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- μ-Opioid Receptor Dynamics in the Parameningeal Tissue During Migraine Attacks.Annals of neurology · 2025Article
- Interleukin-4 induces CD11ceLife · 2025Article
- Associations of non-suicidal self-injury with childhood maltreatment and inflammatory cytokines in adolescents with major depressive disorder.BMC psychiatry · 2025Article
- Toxoplasma gondii chronic infection decreases visceral nociception through peripheral opioid receptor signaling.PLoS pathogens · 2025Article
- Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025Review
- Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies.Journal of orthopaedic translation · 2024Review
- Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.Scientific reports · 2024Article
- Pain-resolving immune mechanisms in neuropathic pain.Nature reviews. Neurology · 2023Review
- Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs.Frontiers in immunology · 2023Review
- M2 macrophage polarization: a potential target in pain relief.Frontiers in immunology · 2023Review
- HDAC6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity via Tonic Delta Opioid Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Amelioration of injury-induced tissue acidosis by a nonsteroidal analgesic attenuates antinociceptive effects of the pH-dependent opioid agonist NFEPP.Scientific reports · 2022Article
- Burning and Scaling Probably Associated with Dupilumab Therapy: A Case Report.Clinical, cosmetic and investigational dermatology · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-4 (IL-4) is an anti-inflammatory cytokine, which can be protective in inflammatory and neurologic disorders, and can alleviate pain. Classically, IL-4 diminishes pain by blocking the production of proinflammatory cytokines. Here, we uncovered that IL-4 induces acute antinociception by IL-4 receptor α (IL-4Rα)-dependent release of opioid peptides from M1 macrophages at injured nerves. As a model of pathologic pain, we used a chronic constriction injury (CCI) of the sciatic nerve in male mice. A single application of IL-4 at the injured nerves (14 d following CCI) attenuated mechanical hypersensitivity evaluated by von Frey filaments, which was reversed by co-injected antibody to IL-4Rα, antibodies to opioid peptides such as Met-enkephalin (ENK), β-endorphin and dynorphin A 1-17, and selective antagonists of δ-opioid, µ-opioid, and κ-opioid receptors. Injured nerves were predominately infiltrated by proinflammatory M1 macrophages and IL-4 did not change their numbers or the phenotype, assessed by flow cytometry and qRT-PCR, respectively. Macrophages isolated from damaged nerves by immunomagnetic separation (IMS) and stimulated with IL-4 dose dependently secreted all three opioid peptides measured by immunoassays. The IL-4-induced release of ENK was diminished by IL-4Rα antibody, intracellular Ca
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