Journal article
Fatigue-enhanced hyperalgesia in response to muscle insult: Induction and development occur in a sex-dependent manner
Pain (Amsterdam), Vol.154(12), pp.2668-2676
12/2013
DOI: 10.1016/j.pain.2013.07.047
PMCID: PMC3957416
PMID: 23906552
Abstract
Characterization of a pre-clinical model of chronic muscle pain in which muscle fatigue combined with a subthreshold muscle insult produces long-lasting, sex-dependent hypersensitivity with minimal tissue damage in mice—findings consistent with clinical observations of chronic muscle pain patients.
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 24hours later. However, female mice also develop hyperalgesia when muscle fatigue and muscle insult occur in different muscles, and when muscle insult is administered 24hours 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.
Details
- Title: Subtitle
- Fatigue-enhanced hyperalgesia in response to muscle insult: Induction and development occur in a sex-dependent manner
- Creators
- Nicholas S Gregory - Neuroscience Program, University of Iowa, USAKatherine Gibson-Corley - Department of Pathology, University of Iowa Carver College of Medicine, USALaura Frey-Law - Department of Physical Therapy and Rehabilitation Science, University of Iowa Carver College of Medicine, USAKathleen A Sluka - Neuroscience Program, University of Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Pain (Amsterdam), Vol.154(12), pp.2668-2676
- DOI
- 10.1016/j.pain.2013.07.047
- PMID
- 23906552
- PMCID
- PMC3957416
- NLM abbreviation
- Pain
- ISSN
- 0304-3959
- eISSN
- 1872-6623
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 12/2013
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984040006902771
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