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AuthorAl-Waeli H.
AuthorNicolau B.
AuthorStone L.
AuthorAbu Nada L.
AuthorGao Q.
AuthorAbdallah M.
AuthorAbdulkader E.
AuthorSuzuki M.
AuthorMansour A.
AuthorAl Subaie A.
AuthorTamimi F.
Available date2022-05-31T19:01:21Z
Publication Date2020
Publication NameScientific Reports
ResourceScopus
Identifierhttp://dx.doi.org/10.1038/s41598-019-57215-y
URIhttp://hdl.handle.net/10576/31827
AbstractPostoperative 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. ? 2020, The Author(s).
Languageen
PublisherNature Research
Subjectnonsteroid antiinflammatory agent
animal
C57BL mouse
chronotherapy
complication
convalescence
drug effect
fracture
gene expression regulation
inflammation
mouse
pathology
postoperative pain
procedures
wound healing
Animals
Anti-Inflammatory Agents, Non-Steroidal
Chronotherapy
Fractures, Bone
Gene Expression Regulation
Inflammation
Mice
Mice, Inbred C57BL
Pain, Postoperative
Recovery of Function
Wound Healing
TitleChronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery
TypeArticle
Issue Number1
Volume Number10
dc.accessType Abstract Only


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