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.
