ArticlePain2016
Regular physical activity prevents chronic pain by altering resident muscle macrophage phenotype and increasing interleukin-10 in mice.
Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 3 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Understanding Exercise-Induced Hypoalgesia: An Umbrella Review of Scientific Evidence and Qualitative Content Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Efficacy and safety of therapeutic exercise for primary dysmenorrhea: a systematic review and meta-analysis.Frontiers in medicine · 2025Pooled it
- The potential protective effects of pre-injury exercise on neuroimmune responses following experimentally-induced traumatic neuropathy: a systematic review with meta-analysis.Frontiers in immunology · 2023Pooled it
- Physical activity is related to function and fatigue but not pain in women with fibromyalgia: baseline analyses from the Fibromyalgia Activity Study with TENS (FAST).Arthritis research & therapy · 2018Trial
- The complexity of pain in osteoarthritis.Nature reviews. Rheumatology · 2026Review
- The changes of inflammatory biomarkers after a 12-week home-based aerobic and resistance exercise intervention in breast cancer survivors.BMC research notes · 2026Article
- High Cardiorespiratory Fitness and Vigorous Physical Activity Relate to Select Pain Sensitivity Assessments in Healthy Adults: A Cross-Sectional Study.Pain research & management · 2026Article
- Review
- Review
- Sex Differences in Strength, Self-Estimation, and Pain Perception Based on Physical Activity After Rotator Cuff Repair.Healthcare (Basel, Switzerland) · 2025Article
- Adaptations in mitochondrial quality control and interactions with innate immune signaling within skeletal muscle: A narrative review.Journal of sport and health science · 2025Review
- Review
- Beneficial Effects of Exercise in Neuropathic Pain: An Overview of the Mechanisms Involved.Pain research & management · 2025Review
- Article
- Role of Exercise on Inflammation Cytokines of Neuropathic Pain in Animal Models.Molecular neurobiology · 2024Review
- Associations of pain sensitivity and conditioned pain modulation with physical activity: findings from the Multicenter Osteoarthritis Study (MOST).Osteoarthritis and cartilage · 2024Observational
- Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies.Frontiers in aging neuroscience · 2024Review
- Hemophilic Arthropathy of the Knee and Its Association with Reduced Muscle Strength and Activation and the Pressure Pain Threshold: A Case-Control Study.Journal of clinical medicine · 2023Article
- Osteopontin May Improve Postinjury Muscle Repair Via Matrix Metalloproteinases And tgf-β Activation in Regular Exercise.International journal of medical sciences · 2023Article
- Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.PloS one · 2023Article
14 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
4 authors at 1 institution in 1 country.
Funding
Abstract
Regular physical activity in healthy individuals prevents development of chronic musculoskeletal pain; however, the mechanisms underlying this exercise-induced analgesia are not well understood. Interleukin-10 (IL-10), an antiinflammatory cytokine that can reduce nociceptor sensitization, increases during regular physical activity. Since macrophages play a major role in cytokine production and are present in muscle tissue, we propose that physical activity alters macrophage phenotype to increase IL-10 and prevent chronic pain. Physical activity was induced by allowing C57BL/6J mice free access to running wheels for 8 weeks and compared to sedentary mice with no running wheels. Using immunohistochemical staining of the gastrocnemius muscle to label regulatory (M2, secretes antiinflammatory cytokines) and classical (M1, secretes proinflammatory cytokines) macrophages, the percentage of M2-macrophages increased significantly in physically active mice (68.5% ± 4.6% of total) compared with sedentary mice (45.8% ± 7.1% of total). Repeated acid injections into the muscle enhanced mechanical sensitivity of the muscle and paw in sedentary animals, which does not occur in physically active mice; no sex differences occur in either sedentary or physically active mice. Blockade of IL-10 systemically or locally prevented the analgesia in physically active mice, ie, mice developed hyperalgesia. Conversely, sedentary mice pretreated systemically or locally with IL-10 had reduced hyperalgesia after repeated acid injections. Thus, these results suggest that regular physical activity increases the percentage of regulatory macrophages in muscle and that IL-10 is an essential mediator in the analgesia produced by regular physical activity.
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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 OpenQuestion graph.