Canada Brain Power

Tag: Pain

  • Discovery of a new mechanism to explain the development of neuropathic pain

    Discovery of a new mechanism to explain the development of neuropathic pain

    Chronic pain is a disease that affects nearly 8 million Canadians and that can lead to a wide range of physical, emotional, and social challenges. Nerve injury can sometimes lead to long-lasting pain hypersensitivity, called neuropathic pain, where pain persists beyond the usual recovery period. Research by Shannon Tansley (done while she was a PhD candidate at McGill University) and colleagues, recently published in the prestigious journal Science, has uncovered a new mechanism for the development of neuropathic pain. Her findings could lead to innovative therapeutic strategies by targeting this newly discovered mechanism.

    Shannon Tansley won the Marlene Reimer Brain Star of the Year award from CAN-CIHR-INMHA for these groundbreaking discoveries.

    Following injury, nerve cells release chemicals that activate nearby cells, including cells called microglia, and promote the transmission of pain messages in the body. Microglia are known to release bioactive substances that directly affect nerve cells, but how they specifically affected only pain transmitting circuits was not understood. Tansley and colleagues investigated the interaction of microglia with perineuronal nets, structural elements which are part of the extracellular matrix which not only provides structural support for neurons but can also be involved in regulating their activity. What they discovered is that microglia mediate the degradation of perineuronal nets that are found specifically around nerve cells that transmit pain signals. The degradation of these perineuronal nets increases the output of pain signals and thereby promotes pain.

    This very innovative work is one of the first comprehensive studies of perineuronal nets in the context of pain. The finding of a novel mechanism by which activated microglia selectively increase pain signaling to evoke pain has the potential to lead to new therapeutic strategies to reverse neuropathic pain by targeting this newly discovered mechanism.

    This finding provides hope for the millions of Canadians living with chronic pain.

    About Shannon Tansley

    Dr. Shannon Tansley completed her PhD under co-supervision by Drs. Arkhady Khoutorsky and Jeffrey Mogil at McGill University, where the work described here was completed. Dr. Tansley conceived all the experimental ideas for this publication, generated most of the data and is lead author on the publication. On top of generating experimental ideas and subsequent data generation, Dr. Tansley effectively troubleshooted all experiments and set up new techniques in the lab in the process.

    Dr. Tansley is currently a Medical Student.

     Sources of funding

    Funding was provided by CIHR, NSERC, and Rita Allen Foundation.

    Scientific publication:

    Tansley S, Gu N, Guzmán AU, Cai W, Wong C, Lister KC, Muñoz-Pino E, Yousefpour N, Roome RB, Heal J, Wu N, Castonguay A, Lean G, Muir EM, Kania A, Prager-Khoutorsky M, Zhang J, Gkogkas CG, Fawcett JW, Diatchenko L, Ribeiro-da-Silva A, De Koninck Y, Mogil JS, Khoutorsky A. Microglia-mediated degradation of perineuronal nets promotes pain. Science. 2022 Jul;377(6601):80-86.

    https://www.science.org/doi/10.1126/science.abl6773

  • Identification of sex-specific differences in pain signaling could lead to better treatment

    Identification of sex-specific differences in pain signaling could lead to better treatment

    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

    https://academic.oup.com/brain/article/145/3/1124/6551129

  • Pain is processed differently in women and men: interview with Michael Hildebrand

    Pain is processed differently in women and men: interview with Michael Hildebrand

    Episode 116 BEaTS Research Radio- Interview with Dr. Michael Hildebrand

    Nicole Chu from the University of Ottawa speaks with Dr. Mike Hildebrand, Associate Professor at Carleton University in the Department of Neuroscience and Affiliate Investigator at the Ottawa Hospital Research Institute. Tune in to learn more about their recent work published in the Journal Brain which demonstrates for the first time that spinal cord process pain signals differently in women compared to men.

    Learn more: https://hildebrandpainlab.com/

    Follow BEaTS Research Radio on youtube https://www.youtube.com/@BEaTSResearchRadio

  • Discovery reveals blocking inflammation may lead to chronic pain

    Discovery reveals blocking inflammation may lead to chronic pain

    Findings may lead to reconsideration of how we treat acute pain

    Using anti-inflammatory drugs and steroids to relieve pain could increase the chances of developing chronic pain, according to researchers from McGill University and colleagues in Italy. Their research puts into question conventional practices used to alleviate pain. Normal recovery from a painful injury involves inflammation and blocking that inflammation with drugs could lead to harder-to-treat pain.

    “For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs. But we found that this short-term fix could lead to longer-term problems,” says Jeffrey Mogil, a Professor in the Department of Psychology at McGill University and E. P. Taylor Chair in Pain Studies.

    The difference between people who get better and don’t

    In the study published in Science Translational Medicine, the researchers examined the mechanisms of pain in both humans and mice. They found that neutrophils – a type of white blood cell that helps the body fight infection – play a key role in resolving pain.

    “In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away. Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils,” says Luda Diatchenko a Professor in the Faculty of Medicine, Faculty of Dentistry, and Canada Excellence Research Chair in Human Pain Genetics.

    Read the full story on the McGill University website