Female chronic pain patients far outnumber males; however, most of the foundational preclinical pain research has been conducted in male rodents only. This has resulted in two barriers to translating basic science findings into new effective clinical treatments: a fundamental lack of knowledge of female pain physiology, and possible species differences between the rodents used in basic science investigations and the human clinical pain population. By combining studies of behaviour in rodents and transmission of pain signals in spinal cord tissue from humans and rodents from both sexes, Annemarie Dedek has successfully bridged the gap between animal and human studies to explain sex differences in chronic pain development. She won a Brain Star award from the Canadian Association for Neuroscience and the Canadian Institutes of Health Research for this ground-breaking discovery.
Annemarie Dedek reports three main findings in this publication:
First, while male and female animals share similar responses to inflammatory pain, the neuronal mechanism underlying this pain differ by sex.
Second, in male rats and humans, loss of inhibition of pain signals, which is associated with the development of chronic pain, depends on brain-derived neurotrophic factor (BDNF), which then affects NMDA receptors in pain-processing neurons of the spinal chord. In female rats and humans pain signalling is driven independently of BDNF and NMDA receptor alterations.
Third, pain processing in female rats whose ovaries were removed before sexual maturity is similar to that seen in males, and dependent on BDNF and NMDA receptors. This indicates that sex differences are driven by sex hormones.
In summary, these results describe sex specific mechanisms of development of pathological pain that is conserved across rats and humans. These findings are evidence of the importance of sex-inclusive basic science research and suggest that clinically effective pain therapies may target sex-specific drivers of pathological pain.
About Dr. Annemarie Dedek
Annemarie Dedek is passionate about helping the over 8 million Canadians living with Chronic pain. She completed this work during her PhD in the laboratories of Dr. Michael Hildebrand at Carleton University and Dr. Eve Tsai at the Ottawa Hospital Research Institute. Working on this project has forever changed her outlook on science. Since working on this project, she is now more cognizant of bias and inequity in research and in medicine. This important discovery has inspired her to work to improve equity in basic science.
Funding Sources
Mitacs, CIHR, NSERC, Eli Lilly, The International Association for the Study of Pain, The Canadian Pain Society
Read more about this story
https://www.eurekalert.org/news-releases/947138
https://ottawacitizen.com/news/local-news/finding-of-sex-related-differences-in-pain-signalling-could-lead-to-better-treatment
This paper has garnered widespread media interest, including on the cover of The Ottawa Citizen, in an interview on CBC radio and with global news outlets across Africa, Asia, Europe, and North America. This study ranked in the top 5% of studies ranked by altmetric, a measure of the publication’s impact in the media https://oxfordjournals.altmetric.com/details/125143422/news
Scientific publication:
Annemarie Dedek, Jian Xu, Louis-Étienne Lorenzo, Antoine G Godin, Chaya M Kandegedara, Geneviève Glavina, Jeffrey A Landrigan, Paul J Lombroso, Yves De Koninck, Eve C Tsai, Michael E Hildebrand, Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain, Brain, Volume 145, Issue 3, March 2022, Pages 1124–1138, https://doi.org/10.1093/brain/awab408
