ArticleMolecular neurobiology2020
P2X4 Receptors on Muscle Macrophages Are Required for Development of Hyperalgesia in an Animal Model of Activity-Induced Muscle Pain.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- A mouse model to study persistent fatigue.Research square · 2026Article
- Sex differences in the transition to chronic pain.The Journal of clinical investigation · 2025Review
- Article
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.Brain, behavior, and immunity · 2024Article
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.bioRxiv : the preprint server for biology · 2023Article
- The Role of Neuro-Immune Interactions in Chronic Pain: Implications for Clinical Practice.Journal of pain research · 2022Review
- Macrophage as a Peripheral Pain Regulator.Cells · 2021Review
- Role of microglia and P2X4 receptors in chronic pain.Pain reports · 2021Review
- P2X Receptors: Potential Therapeutic Targets for Symptoms Associated With Lung Cancer - A Mini Review.Frontiers in oncology · 2021Review
- Purinergic Signaling in Endometriosis-Associated Pain.International journal of molecular sciences · 2020Review
- Grand Challenges in Musculoskeletal Pain Research: Chronicity, Comorbidity, Immune Regulation, Sex Differences, Diagnosis, and Treatment Opportunities.Frontiers in pain research (Lausanne, Switzerland) · 2020Article
- Influence of routine exercise on the peripheral immune system to prevent and alleviate pain.Neurobiology of pain (Cambridge, Mass.)Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Activity-induced pain is common in those with chronic musculoskeletal pain and limits participation in daily activities and exercise. Our laboratory developed a model of activity-induced pain and shows that depletion of muscle macrophages prevents development of hyperalgesia. Adenosine triphosphate (ATP) is released from fatiguing muscle and activates purinergic receptors (P2X), and P2X4 receptors are expressed on macrophages. We hypothesized that exercise releases ATP to activate P2X4 receptors on muscle macrophages, which subsequently release interleukin-1β (IL-1β) to produce hyperalgesia. In an animal model of activity-induced pain, using male and female C57BL6/J mice, we show increased expression of P2X4 on muscle macrophages, and blockade of P2X4 receptors in muscle prevented development of hyperalgesia. Using a lentivirus expressing an artificial micro-RNA to P2X4 under the control of a CD68 promoter, we decreased expression of P2X4 mRNA in cultured macrophages, decreased expression of P2X4 protein in muscle macrophages in vivo, and prevented development of activity-induced hyperalgesia. We further show that macrophages primed with LPS differentially released IL-1β when treated with ATP in neutral or acidic pH. Lastly, blockade of IL-1β in muscle prevented development of hyperalgesia in this model. Thus, our data suggest that P2X4 receptors could be a valid pharmacological target to control activity-induced muscle pain experienced by patients with chronic musculoskeletal pain.
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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 Socratic graph.