Our biological clock plays crucial role in healing from surgery

January 21, 2020

If you have just had knee, shoulder or hip surgery, you may want to take anti-inflammatories in the morning or at noon, but not at night. A McGill-led study shows, for the first time, that circadian clock genes are involved in healing from surgery. Indeed, the researchers demonstrated that anti-inflammatory medications are most effective in promoting post-operative healing and recovery when taken during the active periods of our biological clocks.

The study, recently published in Scientific Reports, also suggests that if anti-inflammatories are taken either in the afternoon or at night, during the resting phases of the circadian rhythm, they can severely deter healing and bone repair following surgery. That's because these are the periods when cells known as osteoblasts are rebuilding bone.

Circadian clock genes involved in healing from surgery

Although prior research has shown that circadian clock genes play a role in diseases such as cancer, Alzheimer's, arthritis and Parkinson's, this is the first study to see the effect of the circadian rhythm in any type of surgery or injury. Faleh Tamimi Marino, the Canada Research Chair for Translational Cranofacial Research is the senior co-author on the article, along with Belinda Nicolau and Laura Stone. All are McGill's Faculty of Dentistry.

Inflammation, following surgery, is crucial to healing since part of the process involves both destroying any bacteria that may be in the area, and signaling to attract the cells that will rebuild the tissues. But the process is not a constant.

"There are periods of inflammation that are actually very destructive, and there are periods that are constructive and important for healing," said Faleh Tamimi. "So many pharmaceutical companies have been trying to develop drugs that will inhibit the destructive processes during inflammation but not interfere with the helpful ones."

He adds, "The idea that I came up with in the shower one morning is that we could perhaps use the circadian variations in inflammation to our advantage. The destructive component of the circadian rhythm as it relates to bone healing occurs during the day, when cells known as osteoclasts break down bones. The constructive cells, known as osteoblasts that rebuild bones are active at night. By limiting the use of anti-inflammatories to the mornings and giving analgesics at night for the pain, I thought we might get better results in terms of bone healing than if anti-inflammatories are given throughout the day."

Significant differences in rates of healing and in genes

The researchers compared pain and bone healing in two different groups of mice with fractured tibia. One group was given constant doses of anti-inflammatories over a twenty-four hour period, while the others were given anti-inflammatories only in the morning - during the active phases of the circadian rhythm - and analgesics at night. The researchers found that the second group recovered from the pain of the injury, and regained bone strength more quickly and more fully. Surprisingly, they also noticed differences between the groups in the expression of over 500 genes specifically related to bone healing processes. "Its almost as if morning anti-inflammatories and evening anti inflammatories were two different drugs" adds Faleh Tamimi.

The rhythm of the body's own healing

"When I was a child, and I cut myself, my mother would say to me, don't worry, go to sleep and tomorrow you will be better," said Haider El-Waeli, the first author on the study, who wrote the paper while working on his PhD at McGill and is now a clinical resident at Dalhousie University. "It turns out she was right because most of the healing happens at night."

"The body has a rhythm," adds Tamimi. "And if you give anti-inflammatories in the morning you are working with the rhythm of the body and when you give them at night, you are working against it so you disrupt the healing."

As a next step, the researchers are collecting preliminary data from a clinical trial monitoring pain and healing related to extraction of wisdom teeth, using two different drug treatments - one involving exclusive use of anti-inflammatories, and the other administering anti-inflammatory medications only in the morning and at noon, and analgesics in the afternoon and evening. The preliminary results are promising.
-end-
To read "Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery" by H. Al-Waeli et al in Scientific Reports doi.org/10.1038/s41598-019-57215-y

The research was funded by: the Canada Research Chair program for Translational Cranofacial Research, the Natural Sciences and Engineering Research Council of Canada (NSERC), the Alpha Omega foundation, the Quebec Network for Bone and Oral Health Research (RSBO) and the Fonds de Recherche du Quebec-Sante (FRQS).

Contact:

Katherine Gombay
McGill Media Relations Office
514-398-2189
katherine.gombay@mcgill.ca

http://www.mcgill.ca/newsroom/http://twitter.com/McGillU

About McGill University

Founded in Montreal, Quebec, in 1821, McGill University is Canada's top ranked medical doctoral university. McGill is consistently ranked as one of the top universities, both nationally and internationally. It is a world-renowned institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. McGill attracts students from over 150 countries around the world, its 12,800 international students making up 31% per cent of the student body. Over half of McGill students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.

McGill University

Related Pain Articles from Brightsurf:

Pain researchers get a common language to describe pain
Pain researchers around the world have agreed to classify pain in the mouth, jaw and face according to the same system.

It's not just a pain in the head -- facial pain can be a symptom of headaches too
A new study finds that up to 10% of people with headaches also have facial pain.

New opioid speeds up recovery without increasing pain sensitivity or risk of chronic pain
A new type of non-addictive opioid developed by researchers at Tulane University and the Southeast Louisiana Veterans Health Care System accelerates recovery time from pain compared to morphine without increasing pain sensitivity, according to a new study published in the Journal of Neuroinflammation.

The insular cortex processes pain and drives learning from pain
Neuroscientists at EPFL have discovered an area of the brain, the insular cortex, that processes painful experiences and thereby drives learning from aversive events.

Pain, pain go away: new tools improve students' experience of school-based vaccines
Researchers at the University of Toronto and The Hospital for Sick Children (SickKids) have teamed up with educators, public health practitioners and grade seven students in Ontario to develop and implement a new approach to delivering school-based vaccines that improves student experience.

Pain sensitization increases risk of persistent knee pain
Becoming more sensitive to pain, or pain sensitization, is an important risk factor for developing persistent knee pain in osteoarthritis (OA), according to a new study by researchers from the Université de Montréal (UdeM) School of Rehabilitation and Hôpital Maisonneuve Rosemont Research Centre (CRHMR) in collaboration with researchers at Boston University School of Medicine (BUSM).

Becoming more sensitive to pain increases the risk of knee pain not going away
A new study by researchers in Montreal and Boston looks at the role that pain plays in osteoarthritis, a disease that affects over 300 million adults worldwide.

Pain disruption therapy treats source of chronic back pain
People with treatment-resistant back pain may get significant and lasting relief with dorsal root ganglion (DRG) stimulation therapy, an innovative treatment that short-circuits pain, suggests a study presented at the ANESTHESIOLOGY® 2018 annual meeting.

Sugar pills relieve pain for chronic pain patients
Someday doctors may prescribe sugar pills for certain chronic pain patients based on their brain anatomy and psychology.

Peripheral nerve block provides some with long-lasting pain relief for severe facial pain
A new study has shown that use of peripheral nerve blocks in the treatment of Trigeminal Neuralgia (TGN) may produce long-term pain relief.

Read More: Pain News and Pain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.