ArticleScientific reports2020
Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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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.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Effect of NSAIDs, melatonin, vitamin D and vitamin B12 chronotherapy on postoperative recovery after third molar surgical extraction: A pilot randomized crossover placebo-controlled trial.Oral and maxillofacial surgery · 2026Trial
- Dexketoprofen Time-Dependent Administration After Third Molar Extraction: A Pilot Randomized Cross-Over Controlled Trial.Clinical and experimental dental research · 2026Trial
- Effect of time-dependent ibuprofen administration on the post operatory after impacted third molar extraction: a cross-over randomized controlled trial.Oral and maxillofacial surgery · 2023Trial
- NSAID chronotherapy after impacted third molar extraction: a randomized controlled trial.Oral and maxillofacial surgery · 2022Trial
- Bone turnover marker rhythmicity: implications for osteoporosis treatment and fracture healing.Endocrine connections · 2026Review
- Development of a Carprofen-Loaded Nanoemulsion for Topical Management of Post-Surgical Inflammation.Pharmaceutics · 2026Article
- Is it time to think about chronotherapy in migraine.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Chronobiology of fracture repair: local molecular clocks, rhythm protection, and time-anchored translation.Frontiers in endocrinology · 2026Review
- NSAID use as a shared decision-making variable in musculoskeletal rehabilitation and strength and conditioning: a perspective.Frontiers in sports and active living · 2026Article
- Reevaluating C-Reactive Protein for Perioperative Risk Stratification: The Overlooked Role of Sleep Apnea in Cardiac Surgery Outcomes.Biomedicines · 2025Article
- Dexamethasone chronotherapy of COVID-19 patients admitted to intensive care unit: an exploratory study.BMC infectious diseases · 2025Article
- The impact of postoperative pain interventions on circadian rhythm disruptions: mechanisms and clinical implications.Frontiers in neuroscience · 2025Review
- At the Intersection of Pain and Sleep: a Roadmap for Preclinical Pain Research.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Nanotechnology in Pain Management.Pharmaceutics · 2024Review
- Nonsteroidal Anti-Inflammatory Drugs Decrease Coagulopathy Incidence in Severe Burn Patients.European burn journal · 2024Article
- Article
- Biomechanics in the onset and severity of spondyloarthritis: a force to be reckoned with.RMD open · 2023Review
- The Efficacy of Curcumin Patch as an Adjuvant Therapeutic Agent in Managing Acute Orofacial Pain on the Post-Cleft Lip and Cleft Palate Surgery Patients: A Pragmatic Trial.European journal of dentistry · 2023Article
- Recent Advances in Chronotherapy Targeting Respiratory Diseases.Pharmaceutics · 2021Review
- The circadian clock and diseases of the skin.FEBS letters · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Postoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment.
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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.