Researchers at the IRCM led by Artur Kania, PhD, uncovered the critical role in pain processing of a gene associated with a rare disease. Their breakthrough, published in The Journal of Neuroscience, paves the way for a better understanding of chronic pain conditions.
Dr. Kania’s team studies the way neural circuits transform harmful stimuli (such as cold, heat, and pinch) into the perception of pain. More precisely, they examined the gene Lmx1b and its involvement in pain processing. Mutations in this gene also cause a rare human disease called the Nail-patella syndrome (NPS), which is characterized by limb and kidney malformations. More importantly, NPS patients show reduced pain responses.
“By studying mouse models, we first showed this gene is essential for the survival of neurons and the development of the spinal cord,” explains Dr. Kania, Director of the Neural Circuit Development research unit at the IRCM. “We then uncovered that removing the gene only in the spinal cord allows the mice to survive. However, it also results in reduced sensitivity to harmful mechanical (crushing, pinching) and thermal (heat, cold) stimulation.”
“We also discovered the missing gene leads to missing neurons, which, in turn, affects the proper development and circuitry of the entire nervous system,” says Nora Szabo, PhD, postdoctoral fellow in Dr. Kania’s laboratory and first author of the study. “In fact, we observed a disruption in the connection between the spinal cord and specific brain centres, which prevents information from being transmitted correctly.”
“Our team was the first to study this gene specifically in the spinal cord,” adds Ronan V. da Silva, PhD student in the same laboratory and co-author of the article. “Our results demonstrate the critical role of Lmx1b for mechanical and thermal pain processing.”
“Seeing as little is currently known about the pain pathways in the nervous system, this breakthrough will help advance our understanding of pain sensation,” states Dr. Kania. “Our work also provides invaluable knowledge for the study of chronic pain and other pain conditions.”
About the research project
The IRCM’s research project was supported by the Quebec Pain Research Network, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, Brain Canada and the W. Garfield Weston Foundation, as well as a McGill/Center for Neuroscience Zurich collaborative project grant and the IRCM’s Angelo-Pizzagalli postdoctoral fellowship. The study was conducted in collaboration with Susana G. Sotocinal and Jeffrey S. Mogil from McGill University and Hanns Ulrich Zeilhofer from the University of Zurich.
About Artur Kania
Artur Kania obtained his PhD in human and molecular genetics from Baylor College of Medicine in Texas, USA. He is Associate IRCM Research Professor and Director of the Neural Circuit Development research unit. Dr. Kania is Assistant Research Professor in the Department of Medicine (accreditation in molecular biology) at the Université de Montréal. He is also Adjunct Professor in the Department of Medicine (Division of Experimental Medicine), the Department of Biology, and the Department of Anatomy and Cell Biology at McGill University. In addition, he is a member of the Centre of Excellence in Neuroscience (CENUM) at the Université de Montréal, and a member of the Quebec Pain Research Network from the Fonds de la recherche du Québec - Santé.
About the IRCM
The IRCM is a renowned biomedical research institute located in the heart of Montréal’s university district. Founded in 1967, it is currently comprised of 35 research units and four specialized research clinics (cholesterol, cystic fibrosis, diabetes and obesity, hypertension). The IRCM is affiliated with the Université de Montréal, and the IRCM Clinic is associated to the Centre hospitalier de l’Université de Montréal (CHUM). It also maintains a long-standing association with McGill University. The IRCM is funded by the Quebec ministry of Economy, Innovation and Export Trade (Ministère de l’Économie, de l’Innovation et des Exportations).
Institut de recherches cliniques de Montreal
Journal of Neuroscience