Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery

H. Al-Waeli; B. Nicolau; L. Stone; L. Abu Nada; Q. Gao; Mn Abdallah; E. Abdulkader; M. Suzuki; A. Mansour; A. Al Subaie; F. Tamimi

doi:10.1038/s41598-019-57215-y

Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery

H. Al-Waeli, B. Nicolau, L. Stone, L. Abu Nada, Q. Gao, Mn Abdallah, E. Abdulkader, M. Suzuki, A. Mansour, A. Al Subaie, F. Tamimi

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English (US)
Article number	468
Journal	Scientific reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-57215-y https://doi.org/10.1038/s41598-019-57215-y
State	Published - Jan 16 2020

Bibliographical note

Funding Information:
The authors would like to acknowldge financial support from the Canada Research Chair program for Translational Cranofacial Research (F.T), the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery program (F.T), the Alpha Omega foundation (H.A), the Quebec Network for Bone and Oral Health Research (RSBO) and the Fonds de Recherche du Quebec-Sante (FRQS). We also thank the Bone Biology Lab, McGill University for providing the space and the scan to perform the CT scan images. Also, we thank the McGill Quebec Genome Center for their help with the gene expression analysis experiment.

Publisher Copyright:
© 2020, The Author(s).

Keywords

Animals
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
Chronotherapy/methods
Fractures, Bone/complications
Gene Expression Regulation
Inflammation/drug therapy
Mice
Mice, Inbred C57BL
Pain, Postoperative/drug therapy
Recovery of Function
Wound Healing/drug effects

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

Find It

Find It at U of M Libraries

Cite this

@article{908415d40a754bf59b402d93a3924c3e,

title = "Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery",

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.",

keywords = "Animals, Anti-Inflammatory Agents, Non-Steroidal/administration & dosage, Chronotherapy/methods, Fractures, Bone/complications, Gene Expression Regulation, Inflammation/drug therapy, Mice, Mice, Inbred C57BL, Pain, Postoperative/drug therapy, Recovery of Function, Wound Healing/drug effects",

author = "H. Al-Waeli and B. Nicolau and L. Stone and {Abu Nada}, L. and Q. Gao and Mn Abdallah and E. Abdulkader and M. Suzuki and A. Mansour and {Al Subaie}, A. and F. Tamimi",

note = "Funding Information: The authors would like to acknowldge financial support from the Canada Research Chair program for Translational Cranofacial Research (F.T), the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery program (F.T), the Alpha Omega foundation (H.A), the Quebec Network for Bone and Oral Health Research (RSBO) and the Fonds de Recherche du Quebec-Sante (FRQS). We also thank the Bone Biology Lab, McGill University for providing the space and the scan to perform the CT scan images. Also, we thank the McGill Quebec Genome Center for their help with the gene expression analysis experiment. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = jan,

day = "16",

doi = "10.1038/s41598-019-57215-y",

language = "English (US)",

volume = "10",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery

AU - Al-Waeli, H.

AU - Nicolau, B.

AU - Stone, L.

AU - Abu Nada, L.

AU - Gao, Q.

AU - Abdallah, Mn

AU - Abdulkader, E.

AU - Suzuki, M.

AU - Mansour, A.

AU - Al Subaie, A.

AU - Tamimi, F.

N1 - Funding Information: The authors would like to acknowldge financial support from the Canada Research Chair program for Translational Cranofacial Research (F.T), the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery program (F.T), the Alpha Omega foundation (H.A), the Quebec Network for Bone and Oral Health Research (RSBO) and the Fonds de Recherche du Quebec-Sante (FRQS). We also thank the Bone Biology Lab, McGill University for providing the space and the scan to perform the CT scan images. Also, we thank the McGill Quebec Genome Center for their help with the gene expression analysis experiment. Publisher Copyright: © 2020, The Author(s).

PY - 2020/1/16

Y1 - 2020/1/16

N2 - 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.

AB - 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.

KW - Animals

KW - Anti-Inflammatory Agents, Non-Steroidal/administration & dosage

KW - Chronotherapy/methods

KW - Fractures, Bone/complications

KW - Gene Expression Regulation

KW - Inflammation/drug therapy

KW - Mice

KW - Mice, Inbred C57BL

KW - Pain, Postoperative/drug therapy

KW - Recovery of Function

KW - Wound Healing/drug effects

UR - http://www.scopus.com/inward/record.url?scp=85077941416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077941416&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-57215-y

DO - 10.1038/s41598-019-57215-y

M3 - Article

C2 - 31949183

AN - SCOPUS:85077941416

SN - 2045-2322

VL - 10

JO - Scientific reports

JF - Scientific reports

IS - 1

M1 - 468

ER -

Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this