ArticlePloS one2015
Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Effects of 5-aminolevulinic acid supplementation on home-based walking training achievement in middle-aged depressive women: randomized, double-blind, crossover pilot study.Scientific reports · 2018Trial
- NMR-based metabolomics in a clinical cohort: deciphering the metabolic characteristics of gout with the dampness-heat syndrome and elucidate the efficacy of Simiao Pill.Chinese medicine · 2026Article
- Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.Brain, behavior, and immunity · 2024Article
- Paraspinal muscle oxygenation and mechanical efficiency are reduced in individuals with chronic low back pain.Scientific reports · 2024Article
- Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.Current neuropharmacology · 2024Review
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.bioRxiv : the preprint server for biology · 2023Article
- Localized Pain and Fatigue During Recovery From Submaximal Resistance Exercise in People With Fibromyalgia.Physical therapy · 2023Observational
- Qigong Exercise Balances Oxygen Supply and Acid-Base to Modulate Hypoxia: A Perspective Platform toward Preemptive Health & Medicine.Medical sciences (Basel, Switzerland) · 2023Article
- Functional Impact of Post-exercise Cooling and Heating on Recovery and Training Adaptations: Application to Resistance, Endurance, and Sprint Exercise.Sports medicine - open · 2022Review
- Is "Delayed Onset Muscle Soreness" a False Friend? The Potential Implication of the Fascial Connective Tissue in Post-Exercise Discomfort.International journal of molecular sciences · 2021Review
- P2X4 Receptors on Muscle Macrophages Are Required for Development of Hyperalgesia in an Animal Model of Activity-Induced Muscle Pain.Molecular neurobiology · 2020Article
- Effects of Lactate on One Class of Group III (CT3) Muscle Afferents.Frontiers in cellular neuroscience · 2020Article
- Chronic non-inflammatory muscle pain: central and peripheral mediators.Current opinion in physiology · 2019Article
- Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2018Article
- Sex differences in primary muscle afferent sensitization following ischemia and reperfusion injury.Biology of sex differences · 2018Article
- Peripheral Mechanisms of Ischemic Myalgia.Frontiers in cellular neuroscience · 2017Review
- Influence of routine exercise on the peripheral immune system to prevent and alleviate pain.Neurobiology of pain (Cambridge, Mass.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.
Indexed as
Identifiers
What Socratic 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 Socratic graph.