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• W2045396370 startingPage "1020" @default.
• W2045396370 abstract "An acute bout of exercise can exacerbate pain, hindering participation in regular exercise and daily activities. The mechanisms underlying pain in response to acute exercise are poorly understood. We hypothesized that proton accumulation during muscle fatigue activates acid-sensing ion channel 3 (ASIC3) on muscle nociceptors to produce hyperalgesia. We investigated the role of ASIC3 using genetic and pharmacological approaches in a model of fatigue-enhanced hyperalgesia. This model uses two injections of pH 5.0 saline into muscle in combination with an electrically induced fatigue of the same muscle just prior to the second injection of acid to induce mechanical hyperalgesia. We show a significant decrease in muscle force and decrease in muscle pH after 6 min of electrical stimulation. Genetic deletion of ASIC3 using knockout mice and pharmacological blockade of ASIC3 with APETx2 in muscle prevents the fatigue-enhanced hyperalgesia. However, ASIC3(-/-) mice and APETx2 have no effect on the fatigue response. Genetic deletion of ASIC3 in primary afferents innervating muscle using an HSV-1 expressing microRNA (miRNA) to ASIC3 surprisingly had no effect on the development of the hyperalgesia. Muscle fatigue increased the number of macrophages in muscle, and removal of macrophages from muscle with clodronate liposomes prevented the development of fatigue-enhanced hyperalgesia. Thus, these data suggest that fatigue reduces pH in muscle that subsequently activates ASIC3 on macrophages to enhance hyperalgesia to muscle insult." @default.
• W2045396370 created "2016-06-24" @default.
• W2045396370 creator A5033030904 @default.
• W2045396370 creator A5062314731 @default.
• W2045396370 creator A5076519526 @default.
• W2045396370 creator A5089125420 @default.
• W2045396370 date "2015-01-11" @default.
• W2045396370 modified "2023-10-14" @default.
• W2045396370 title "ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia" @default.
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• W2045396370 doi "https://doi.org/10.1007/s12035-014-9055-4" @default.
• W2045396370 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4499332" @default.
• W2045396370 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25577172" @default.
• W2045396370 hasPublicationYear "2015" @default.
• W2045396370 type Work @default.

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