ArticleJCI insight2020
IL-4 induces M2 macrophages to produce sustained analgesia via opioids.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 139 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Fibrin-rich environment drives catheter-associated UTIs by suppressing macrophage defenses.Nature communications · 2026Article
- Associations between preoperative biomarkers and patient-reported outcomes after single-level lumbar discectomy: a systematic review.Journal of spine surgery (Hong Kong) · 2026Review
- Whole-body vibration decreases pain and cartilage degeneration in male and female mice with osteoarthritis.Pain reports · 2026Article
- Monocyte-derived IL-10 drives sex differences in pain duration.Science immunology · 2026Article
- Article
- Molecular and Cellular Mechanism of Acupuncture: Neuro-Immune Interactions Based on Endogenous Opioid System.Chinese journal of integrative medicine · 2026Review
- The Impacts of Local Anesthetics and Surgical Trauma on Immunity.Veterinary medicine international · 2026Review
- Cellular and molecular changes in the skin driving increased nociception and pain during burn injury and repair.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Contribution of immune cells and cytokines to radiation-induced injury: the key roles and potential targets.Frontiers in immunology · 2026Review
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- Precision Glyco-Modulation of Macrophages with EF-M2 (ImmutalonVeterinary sciences · 2025Article
- Identification of Neurotrophic Factor Related Biomarkers and Mechanistic Insights into Neuropathic Pain via Integrated Bioinformatics Analysis.ACS omega · 2025Article
- Interleukin-4 induces CD11ceLife · 2025Article
- Article
- Effect ofMolecules (Basel, Switzerland) · 2025Article
- Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025Review
- Reprogramming Macrophage Phenotypes With Photobiomodulation for Improved Inflammation Control in ENT Organ Tissues.Clinical and experimental otorhinolaryngology · 2025Article
- The analgesic mechanism of electroacupuncture at the central level for neuropathic pain: a review of studies based on animal experiments.Frontiers in neurology · 2025Review
- Cellular senescence in the innervated niche modulates cancer-associated pain: an emerging therapeutic target?Frontiers in immunology · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-4 is a pleiotropic antiinflammatory cytokine, which can be neuroprotective after nervous system injury. The beneficial actions of IL-4 are thought to result from the blunting of action of inflammatory mediators, such as proinflammatory cytokines. Here, we demonstrate that IL-4 induces M2 macrophages to continuously produce opioid peptides and ameliorate pain. IL-4 application at injured nerves in mice shifted F4/80+ macrophages from the proinflammatory M1 to the antiinflammatory M2 phenotype, which synthesized opioid peptides (Met-enkephalin, β-endorphin, and dynorphin A 1-17). These effects were accompanied by a long-lasting attenuation of neuropathy-induced mechanical hypersensitivity, beyond the IL-4 treatment. This IL-4-induced analgesia was decreased by opioid peptide antibodies and opioid receptor (δ, μ, κ) antagonists applied at injured nerves, which confirms the involvement of the local opioid system. The participation of M2 macrophages was supported by analgesia in recipient mice injected at injured nerves with F4/80+ macrophages from IL-4-treated donors. Together, IL-4-induced M2 macrophages at injured nerves produced opioid peptides, which activated peripheral opioid receptors to diminish pain. Fostering the opioid-mediated actions of intrinsic M2 macrophages may be a strategy to tackle pathological pain.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.