ArticlePain2013
Fatigue-enhanced hyperalgesia in response to muscle insult: induction and development occur in a sex-dependent manner.
Article in Pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 68 citations in OpenAlex.
- 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
- A mouse model to study persistent fatigue.Research square · 2026Article
- The effect of fascia gun on relaxation of exercise-induced muscle fatigue in athletes: a randomized controlled trial.Frontiers in sports and active living · 2026Article
- [Comorbidity of chronic pain and fatigue : Common mechanisms, common treatment steps?]Schmerz (Berlin, Germany) · 2025Review
- Sex differences in the transition to chronic pain.The Journal of clinical investigation · 2025Review
- Hyperalgesic Priming in the Transition From Acute to Chronic Pain: Focus on Different Models and the Molecular Mechanisms Involved.Journal of pain research · 2025Review
- Article
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.Brain, behavior, and immunity · 2024Article
- The Fibromyalgia Pain Experience: A Scoping Review of the Preclinical Evidence for Replication and Treatment of the Affective and Cognitive Pain Dimensions.Biomedicines · 2024Article
- Topical application of a TRPA1 antagonist reduced nociception and inflammation in a model of traumatic muscle injury in rats.Inflammopharmacology · 2023Article
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.bioRxiv : the preprint server for biology · 2023Article
- Pain interference and fatigue in limb-girdle muscular dystrophy R9.Neuromuscular disorders : NMD · 2023Article
- Chronic pain, chronic stress and substance use: overlapping mechanisms and implications.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Translating Outcomes from the Clinical Setting to Preclinical Models: Chronic Pain and Functionality in Chronic Musculoskeletal Pain.Pain medicine (Malden, Mass.) · 2022Article
- Innovations and advances in modelling and measuring pain in animals.Nature reviews. Neuroscience · 2022Review
- Acid-sensing ion channel 3: An analgesic target.Channels (Austin, Tex.) · 2021Review
- Review
- Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update.International journal of molecular sciences · 2021Review
- Article
- P2X3 receptors contribute to transition from acute to chronic muscle pain.Purinergic signalling · 2020Article
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
Chronic muscle pain affects 20-50% of the population, is more common in women than men, and is associated with increased pain during physical activity and exercise. Muscle fatigue is common in people with chronic muscle pain, occurs in response to exercise, and is associated with release of fatigue metabolites. Fatigue metabolites can sensitize muscle nociceptors, which could enhance pain with exercise. Using a mouse model we tested whether fatigue of a single muscle, induced by electrical stimulation, resulted in enhanced muscle hyperalgesia and if the enhanced hyperalgesia was more pronounced in female mice. Muscle fatigue was induced in combination with a sub-threshold muscle insult (2 injections of pH 5.0 saline) in male and female mice. We show that male and female mice, fatigued immediately prior to muscle insult in the same muscle, develop similar muscle hyperalgesia 24 hours later. However, female mice also develop hyperalgesia when muscle fatigue and muscle insult occur in different muscles, and when muscle insult is administered 24 hours after fatigue in the same muscle. Further, hyperalgesia lasts significantly longer in females. Finally, muscle insult with or without muscle fatigue results in minimal inflammatory changes in the muscle itself, and sex differences are not related to estradiol (ovariectomy) or changes in brainstem activity (pNR1). Thus, the current model mimics muscle fatigue-induced enhancement of pain observed in chronic muscle pain conditions in the human population. Interactions between fatigue and muscle insult may underlie the development of chronic widespread pain with an associated female predominance observed in human subjects.
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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.