Annemarie Dedek, Carleton University
Annemarie Dedek, Jian Xu, Chaya M Kandegedara, Louis-Étienne Lorenzo, Antoine G Godin, Yves De Koninck, Paul J Lombroso, Eve C Tsai, Michael E Hildebrand, Loss of STEP61 couples disinhibition to N-methyl-D-aspartate receptor potentiation in rodent and human spinal pain processing, Brain, Volume 142, Issue 6, June 2019, Pages 1535–1546, https://doi.org/10.1093/brain/awz105 (open access)
Annemarie Dedek lives and works in Ottawa, Ontario.
Bridging the gap between animal models and human clinical trials for Chronic Pain
Amid the opioid epidemic, and while one in five Canadians live with chronic pain, there is an unprecedented need for new analgesics that are both safe and effective. Analgesic development depends on findings in animal models, but these findings have a high failure rate when applied in clinical trials. This high failure rate may be partially due to the interspecies gap between rodent basic science investigations and human clinical trials.
To close this gap, Annemarie Dedek, a Ph.D. student working with supervisors Dr. Mike Hildebrand at Carleton University and Dr. Eve Tsai at The Ottawa Hospital, has performed the first-ever patch clamp recordings on human spinal cord tissue and developed a novel translational human tissue model of chronic pain. This unique achievement is a great leap forward for understanding human pain physiology. They are the only group in Canada using human spinal cord tissue, and one of only a handful of labs pursuing the endeavor worldwide. They hope that their human pain model will be applied widely as a preclinical validation method to help bridge the gap between basic science and clinical trials. In fact, they are actively collaborating with researchers in the US and Europe to leverage this model for even greater understanding of spinal physiology.
Chronic pain arises when there is an imbalance between excitation and inhibition of neurons in a region of the spinal cord called the superficial dorsal horn (SDH). This leads to a disease-causing increase in transmission of pain signals, a process called potentiation. The mechanisms underlying this imbalance remain unclear in rodent models, and unexplored in humans. Dedek has shown the loss of a protein called STEP6 is both necessary and sufficient to cause potentiation in rodent chronic pain models. Furthermore, using the newly developed human tissue model of chronic pain, they were able to demonstrate the clinical relevance of their findings, by showing that a similar chain of molecular changes occurs in human tissues as was observed in rodent models following treatment with a compound that causes potentiation.
Annemarie Dedek performed this work as a Ph.D. student in the laboratories of Dr. Mike Hildebrand at Carleton University and Dr. Eve Tsai at the Ottawa Hospital. She was invited to present this paper’s findings at several international conferences with the American Pain Society and the International Association for the Study of Pain, where they were enthusiastically received by both basic science and clinician researchers. Indeed, the important translational implications in this paper have been featured through stories on the influential website Pain Research Forum and RELIEF News.
This project was supported by a John R. Evans Leaders Fund grant from the Canada Foundation for Innovation (M.E. Hildebrand), a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (M.E. Hildebrand), an Early Career Research Grant from the International Association for the Study of Pain (M.E. Hildebrand; A.G. Godin), an Early Career Investigator Pain Research Grant from the Canadian Pain Society and Pfizer Canada (M.E. Hildebrand), and Project/Operating Grants from the Canadian Institutes of Health Research (M.E. Hildebrand, 388432; Y. De Koninck, 12942).