ArticlePain2018
Interleukin-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain.
Article in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 6 of them syntheses that pooled it.
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
86 citing papers in PubMed, 6 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- The effect of exercise in the treatment of lumbar disc herniation: a systematic review.Acta neurologica Belgica · 2025Pooled it
- Understanding Exercise-Induced Hypoalgesia: An Umbrella Review of Scientific Evidence and Qualitative Content Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Effect of Type and Dose of Exercise on Neuropathic Pain After Experimental Sciatic Nerve Injury: A Preclinical Systematic Review and Meta-Analysis.The journal of pain · 2023Pooled it
- The effects of aerobic exercise on neuroimmune responses in animals with traumatic peripheral nerve injury: a systematic review with meta-analyses.Journal of neuroinflammation · 2023Pooled 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
- Global Research on Neuropathic Pain Rehabilitation over the Last 20 Years.Neural plasticity · 2021Pooled it
- Swimming Exercise Ameliorates Neuropathic Pain and Is Associated with Hippocampal H19, miR-22, and Wnt/β-Catenin Signaling.Neuromolecular medicine · 2026Article
- Therapeutic Effects of Spent Ground Coffee Oil on Nociception, Anxiety- and Depression-Like Behaviors, and Inflammatory Mechanisms in a CFA-Induced Intraplantar Inflammation Model in Mice.Molecular neurobiology · 2026Article
- Role Shift of Glial Cells from Physiology to Pathology in Alzheimer's Disease: The Regulatory Impact of Exercise.Neuroscience bulletin · 2026Review
- (Cost-)Effectiveness of personalised multimodal physiotherapy compared to surgery in patients with painful cervical radiculopathy. Protocol for a randomised non-inferiority trial (The MOVE-IT study).Contemporary clinical trials communications · 2026Article
- TGF-β1 modulates PFC glial cell activation to facilitate exercise-induced analgesia in mice with spared nerve injury.IBRO neuroscience reports · 2026Article
- Pain-responsive to digital self-management in lumbar disc herniation: the mediating role of patient activation and the moderating effect of pain intensity.BMC health services research · 2026Article
- Systemic Interleukin-4 Application Promotes Functional Recovery and Reprograms Neuroinflammatory and Molecular Responses after Spinal Cord Injury in Rats.Theranostics · 2026Article
- [Mechanisms of spinal microglia and astrocytes in exercise-induced analgesia].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Review
- Sex differences in the transition to chronic pain.The Journal of clinical investigation · 2025Review
- Platinum Deposition in the Central Nervous System: A Novel Insight into Oxaliplatin-induced Peripheral Neuropathy in Young and Old Mice.Molecular neurobiology · 2025Article
- Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025Review
- Exerkines mitigating Alzheimer's disease progression by regulating inflammation: Focusing on macrophage/microglial NLRP3 inflammasome pathway.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Mechanisms of comorbidity between Alzheimer's disease and pain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
26 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 3 institutions in 2 countries.
Funding
Abstract
Peripheral nerve injury (PNI) activates the immune system, resulting in increased proinflammatory cytokines at the site of injury and in the spinal cord dorsal horn. Exercise modulates the immune system promoting an anti-inflammatory phenotype of macrophages in uninjured muscle, and increases in anti-inflammatory cytokines can promote healing and analgesia. We proposed that PNI will decrease, and treadmill exercise will increase, release of anti-inflammatory cytokines at the site of injury and in the spinal cord. We show that 2 weeks of treadmill exercise improves neuropathic pain behaviors in mice: mechanical hyperalgesia, escape and avoidance behavior, and spontaneous locomotor activity. Peripheral nerve injury reduced anti-inflammatory cytokines (interleukin-4 [IL-4], IL-1ra, and IL-5) at the site of nerve injury and in the spinal dorsal horn, whereas exercise restored IL-4, IL-1ra, and IL-5 concentrations to preinjury levels. IL4 mice and mice treated with IL-4 antibody did not develop analgesia to treadmill exercise. Using immunohistochemical staining of the sciatic nerve, treadmill exercise increased the percentage of M2 macrophages (secretes anti-inflammatory cytokines) and decreased M1 macrophages (secretes proinflammatory cytokines) when compared with sedentary mice. The increased M2 and decreased M1 macrophages in exercised mice did not occur in IL-4 mice. In the spinal cord, PNI increased glial cell activation, brain-derived neurotrophic factor and β-nerve growth factor levels, and decreased IL-4 and IL-1ra levels, whereas treadmill exercise suppressed glial cells activation (Glial Fibrillary Acidic Protein and Iba1 immunoreactivity), reduced brain-derived neurotrophic factor and β-nerve growth factor, and increased IL-4, IL-1ra, and IL-5 concentrations. Our results suggest that IL-4 mediates the analgesia produced by low-intensity exercise by modulating peripheral and central neuroimmune responses in mice with neuropathic 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.