Adjunct Professor of Pharmacology & Therapeutics, McGill University;
Director, Division of Cellular &Molecular Neuroscience, Institut universitaire en santé mentale de Québec;
Scientific Director, Quebec Pain Research Network;
Past-President, Canadian Association for Neuroscience
The Price of Pain
Chronic pain is one of the leading causes of disability in Canada, affecting more than 20 percent of the population – with age, this number can climb to a staggering 50 percent. On an economic front, the Canadian Pain Society estimates that chronic pain costs Canada $55-60 billion per year, including health care expenses and lost productivity.
“This is a silent epidemic that is not truly recognized by society,” says Dr. Yves De Koninck, Professor of Psychiatry and Neuroscience at Laval University and Scientific Director at the Quebec Pain Research Network. “Very few physicians are adequately equipped to deal with chronic pain in their practice and the subject is either poorly addressed or simply not addressed at all during student medical training. Needless to say, this is surprising, considering chronic pain is the second leading cause of suicide among the elderly in Canada."
The suffering experienced by many with chronic pain is the result of neuropathic pain, or pain caused by damage to the nervous system from accidents (spinal cord injuries, amputations), illnesses such as diabetes, shingles and cancer, or drug treatments such as some anti-cancer drugs. Due to abnormalities in the transmission of pain signals between nerve cells, the spinal cord and the brain, even a gentle touch can cause excruciating pain in such cases.
“Many chronic-pain syndromes still are not being treated adequately,” says Dr. DeKoninck. “Complete pain control is rarely achieved, and the incidence of disabling side effects remains very high.”
A Pioneer in Understanding Pain
Dr. De Koninck’s scientific discoveries in the field of pain research are world-renown and have spurred the development of newtreatmentsfor pain management. He has not only made key contributions to ourfundamental understanding of the neurochemistry of pain transmission, but to how pain transmission is specifically altered in chronic pain syndromes. By honing in on the chemical mechanisms associated with the transmission of painin the spinal cord, Dr. De Koninck has not only transformed our understanding of what is going wrong in the nervous system when chronic-pain syndromes occur, but also our understanding of what makes a normal pain signal become intolerable (hyperalgesia) and why a normally non-painful signal can sometimes trigger highly debilitating abnormal pain (allodynia).
“When I began this research over 25 years ago, it was a taboo topic to work on pain,” says Dr. De Koninck. “The medical community’s attitude towards pain has shifted, though, along with the research. Instead of seeing it as a symptom of something else, medical professionals are now beginning to recognize that pain is a problem in itself and, in fact, the most debilitating factor in many of the illnesses they treat.”
One of his leading discoveries – selected as one of the top ten discoveries by the influential magazine Quebec Science –involved delving deeply into the inflammation process that occurs within the spinal cordafter an injury, after extended periods on certain medications, or as a result of certain diseases like diabetes.
What Dr. De Koninck found was that theinflammation process produces not one, but a cascade of events leading to a loss of inhibitory control over the neurons that relay the pain signals to the brain. More amazingly, he discovered that this loss of control results from the dysfunction of a single protein called KCC2 which makes the pain-relay neurons react in an erroneous, exaggerated way – the result is the production of a signal that the brain abnormally interprets as pain when it normally wouldn’t.
“Our findings support the idea that chronic pain results from a dysfunction of the central nervous system,” explains Dr. De Koninck. This represents a major paradigm shift from the earlier view that pain is only an alarm signal, the consequence of another problem and not a problem on its own. “With this insight we are witnessing a transformation in our health-care system, in the way that care is organized, and also in the pharmaceutical industry’s approach to pain,” says Dr. De Koninck.
Dr. De Koninck’s initial discoveries have led him and his team to establish a research program for systematically developing new compounds that restore the normal function of the KCC2 protein and thereby re-establish normal inhibitory control in the nervous system. Theprogram has already produced several potential analgesics that he is currently studying with the goal of producing new medications for chronic pain. It has also yielded a start-up biopharmaceutical company, Chlorion, engaged in the development of therapeutics that act via the modulation of chloride transport in neurons of the spinal cord and the brain for the treatment of neuropathic pain and epilepsy.
“All of these developments can only benefit the patients who are coping with a problem that completely saps their quality of life,” says Dr. De Koninck.
Light Years Ahead
Dr. De Koninck’s innovative research has also led to the development of several new enabling biomedical technologies for neuroscience, including a tiny optical sensing device (called a micro-optrode) capable of quite literally illuminating a single neuron at a time, deep inside the brain – a feat that will allow Dr. De Koninck and his colleagues to examine the workings of neurons in finer detail than ever before.
"The brain,” he says, “is the final frontier in biology and drugs that directly act on the brain are the drugs of the future. “Tools like the micro-optrode will allow us to observe their effects more closely than ever, and develop new treatments for brain diseases, such as chronic pain.”
Dr. De Koninck is often noted for his remarkable creativity, exemplified by such technical ingenuity and for theground-breaking efforts he has made to bridge disparate scientific disciplines. In 2002, he launched an innovative trans-disciplinary training programat Laval University that brings together the fields ofphotonics, computational science and neuroscience.
The success of the program not only led to an entire new avenue of research and training, including the creation of the first graduate program in Biophotonics in North America, but also to the creation of the Neurophotonics Center at Laval, a unique, state-of-the-art facility for advanced biophotonics approaches dedicated to understanding the brain and the development of diagnostics for brain disorders and phototherapy.
Lineage and Legacy
Son of the famous Quebec philosopher Thomas De Koninck,Dr. De Koninck was born in the United States but grew up in Canada. After studying biology at Laval University, a young Dr. De Koninck earned his Ph.D. in Physiology from McGill in 1991 and subsequently worked for several years in the United States before returning to McGill in 1995 to work in their Department of Pharmacology & Therapeutics. It wasn’t until 2000 that he came full circle,returning to Laval, though this time not as a student, but as Director of Cellular & Molecular Neuroscience at the Quebec Mental Health Institute.
National and international peer recognition for Dr. De Koninck’s contributions to the health sciences is not easily surpassed. As a highly sought after as a lecturer,he has been invited to deliver more than 130 lectures across Canada, the United States, Europe, the Middle East and Asia, including talks at the prestigious World Congress on Pain, the Word Institute of Pain, The Patrick Wall Lecture of the British Pain Society, and a Special Lecture before more than 4000 people at the Society for Neuroscience Annual Meeting. His expertise is also highly solicited by leading scientific journals including Nature, Nature Neuroscience, Nature Medicine, Nature Methods, PNAS, Neuron and Journal of Neuroscience for which he regularly reviews several papers each year.
A Leader in Outreach and Service
Beyond this wide recognition of his expertise, Dr. De Koninck is also distinguished by his strong scientific and organisational leadership, not only within his own university, but across Canada and around the world. His contributions to the promotion and growth of neuroscience in Canada are plentiful, and include serving on multiple advisory and review bodies for several provincial, federal and foreign agencies.
Dr. De Koninck has also served as president of the Canadian Association for Neuroscience, during which time he played an instrumental role in enabling the launch of the Canadian Brain Research Fund, a $200M public/private endeavour resulting from a highly synergistic collaboration between Brain Canada and the Canadian Association for Neuroscience in partnership with several health organizations across the country.
Always cognizant of the major health crisis posed by pain, as well as the need to better understand the nature pain itself, Dr. De Koninck’s dedication to advancing health sciences and promoting health care deliveryis abundantly evident in his role as founding director of the Quebec Pain Research Network (QPRN). Comprised of 75 doctors and researchers from Laval, McGill, Montreal and Sherbrooke specialized in the field of chronic pain, the Network conducts research and education to improve the understanding of chronic pain and the effectiveness of diagnosis and treatment.
"Chronic pain is a silent epidemic, devastating and debilitating,” says Dr. De Koninck. “Doctors and patients desperately need more knowledge and treatment options, and it’s my goal that the Quebec Pain Research Network will provide both."