Evidence map›Paper›PMID 42399740›Full record

Trial reportSkeletal muscle2026

NSAIDs trigger drug-specific response to exercise: a multi-omics systems biology analysis of a randomized crossover trial.

Brandon M Roberts, Alexander B Lawrence, Swapna Kannan, Alyssa V Geddis, Cara E Sczuroski, Jess A Gwin, Candace Moyler, Allison Hoke, Aarti Gautam, Jeffery S Staab and 3 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Skeletal muscle, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05512013 (The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

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.

NCT05512013 phase1completednot on this map

The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans

TypeinterventionalSponsorUnited States Army Research Institute of Environmental MedicineRan2022 to 2023Enrolled12ConditionsBone Resorption, Stress Fracture, Bone InjuryArmsIbuprofen 800 mg, Celecoxib 200mg, Flurbiprofen 100 mg, Placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Brandon M RobertsUS Army Research Institute of Environmental Medicine, Natick, MA, USA. Robertsb21@gmail.com.
Alexander B LawrenceMedical Readiness Systems Biology, CMPN, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Swapna KannanMedical Readiness Systems Biology, CMPN, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Alyssa V GeddisUS Army Research Institute of Environmental Medicine, Natick, MA, USA.
Cara E SczuroskiUS Army Research Institute of Environmental Medicine, Natick, MA, USA.
Jess A GwinUS Army Research Institute of Environmental Medicine, Natick, MA, USA.
Candace MoylerMedical Readiness Systems Biology, CMPN, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Allison HokeMedical Readiness Systems Biology, CMPN, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Aarti GautamMedical Readiness Systems Biology, CMPN, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Jeffery S StaabUS Army Research Institute of Environmental Medicine, Natick, MA, USA.
Ronald W MathenyMilitary Operational Medicine Research Program, Fort Detrick, MD, USA.
Rasha Hammamieh *Medical Readiness Systems Biology, CMPN, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Nabarun Chakraborty *Medical Readiness Systems Biology, CMPN, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are widely used by athletes and those who exercise, yet their influence on the molecular responses to exercise remains unclear. Prior studies have often focused on a limited set of molecular pathways, potentially overlooking broader regulator effects of NSAIDs on skeletal muscle signaling. Therefore, we conducted a systems biology study of skeletal muscle biopsies taken before and after exercise, in combination with NSAID consumption, using transcriptomics and metabolomics, to identify differentially enriched pathways and biofunctions.

methodsWe conducted a randomized, counterbalanced, double-masked, crossover trial (NCT05512013) in which 12 healthy adults ingested ibuprofen (IBU, 800 mg), celecoxib (CEL, 200 mg), flurbiprofen (FLU, 100 mg), or placebo (PLA) before a 10 × 10 bout of plyometric exercise. Skeletal muscle biopsies were collected before NSAID consumption and three hours post-exercise. Whole transcriptome profiling was performed using RNA-seq, and the metabolomics profile was assessed via untargeted mass spectrometry. Differential expression analysis and pathway enrichment were used to evaluate NSAID-specific effects across biological domains.

resultsFLU regulated the largest number of differentially expressed transcripts, followed by IBU and CEL. All NSAIDs activated immune-related gene networks and reversed exercise-induced lipid catabolism, with IBU enhancing adaptive immune signaling and CEL modulating both innate and adaptive pathways. Muscle remodeling pathways, including angiogenesis and cell migration, were activated across all NSAIDs, though cachexia-related genes were also upregulated. Interestingly, FLU uniquely upregulated transcripts involved in neuritogenesis.

conclusionNSAIDs trigger drug-specific molecular responses in skeletal muscle post-exercise, affecting early recovery through changes in immune, metabolic, and neuronal signaling.

Indexed as

Anti-Inflammatory Agents, Non-SteroidalExerciseMuscle, SkeletalAdultCross-Over StudiesDouble-Blind MethodFemaleGene Expression ProfilingHumansMaleMetabolomicsMultiomicsSystems BiologyTranscriptomeYoung AdultAnti-Inflammatory Agents, Non-SteroidalExerciseInflammationMetabolomicsMusculoskeletalMyokinesSignaling

Identifiers

PMID42399740
PMCPMC13632184

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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.