Nonsteroidal anti-inflammatory drugs and acetaminophen ameliorate muscular mechanical hyperalgesia developed after lengthening contractions via cyclooxygenase-2 independent mechanisms in rats.
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ABSTRACT:
SUBMITTER: Shimodaira T
PROVIDER: S-EPMC6834261 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Nonsteroidal anti-inflammatory drugs and acetaminophen ameliorate muscular mechanical hyperalgesia developed after lengthening contractions via cyclooxygenase-2 independent mechanisms in rats.
Shimodaira Tetsuhiro T Mikoshiba Shigeo S Taguchi Toru T
PloS one 20191106 11
Nonsteroidal anti-inflammatory drugs and acetaminophen are cyclooxygenase inhibitors commonly used as symptomatic medicines for myofascial pain syndrome. Using the selective inhibitors celecoxib and zaltoprofen, cyclooxygenase-2 has been shown to be involved in the initiation, but not the maintenance, of muscular mechanical hyperalgesia induced by lengthening contractions, which serves as a useful model for the study of myofascial pain syndrome. The effect of other cyclooxygenase-2 inhibitors, s ...[more]
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Project description:To help elucidate mechanistic differences between lengthening and shortening muscle contractions we compared changes in gene expression within 24 h of an acute bout of each type of contraction in the quadriceps. Three healthy young men performed shortening contractions with one leg while the contralateral leg performed lengthening contractions. Biopsies were taken from both legs before exercise, 3, 6, and 24 h afterwards. Expression profiling was performed using a custom-made Affymetrix MuscleChip containing probesets of approximately 3,300 known genes and ESTs expressed in skeletal muscle. We identified 49 genes differentially regulated between the lengthening and shortening contractions. Using unsupervised hierarchical clustering, we identified four distinct clusters, three of which corresponded to unique functional categories (protein synthesis, stress response/early growth, and sarcolemmal structure). The results suggest distinct molecular pathways as early as 3 h post exercise. The molecular differences might contribute to mechanisms underlying the physiological adaptations seen with training using the two modes of exercise. Keywords: Time Series Design
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Project description:I. Experimental Design: a. Type of experiment: Time course b. Experimental factors: 3 month old mice subjected to lengthening contractions of the extensor digitorum longus muscle (EDL). Samples of EDL collected at 6 and 72 h and compared to non-treated control. c. How many hybridizations in exp: 9 d. Common reference used for all hyb: no e. Quality control steps: All arrays used from same lot. Triplicate hybridizations performed for each time point. II. Samples used, extracts, preparation and labeling: Animals. Nine male C57BL/6 mice (3-4 mo of age, 27.8 ± 3.3 g body mass, Harlan Sprague-Dawley, Indianapolis, IN). Muscle Injury. The extensor digitorum longus (EDL) muscle of six mice were exposed to lengthening contractions. Mice were anesthetized with 2% avertin (0.015 ml/kg) and supplemental doses were administered if the mouse responded to a toe pinch. Animals were placed on a plexiglass platform that was maintained at 37°C. 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Project description:The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug-drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug-drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk.
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