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Transforming research on chronic pain

Team
Team leader: Dr. Michael W. Salter, University of Toronto
Members: Dr. Karen D. Davis, University of Toronto; Dr. Yves De Koninck, Université Laval; Dr. Jeffrey Mogil, McGill University; Dr. Min Zhuo, University of Toronto

Project Overview
Pain affects millions of people worldwide and has a profound negative effect on quality of life. Untreated pain is the most common cause of disability that impairs life. Acute pain is a normal sensation triggered by the nervous system to alert the body to an injury. Chronic pain, on the other hand, is a pain that lasts long after the usual recovery period of the initial injury or illness and may even be present without a cause. This sort of pain poses no known defensive or helpful function.

Neuropathic pain is a type of chronic pain that occurs after nerve injury or from disease, where the signs of original injury are gone. It is extremely debilitating and is resistant to available treatments. Neuropathic pain can be seen in patients with diabetes, cancer, HIV and other disorders.

The goal this project was to gain new insights into the genetic, molecular and cellular mechanisms regarding why pain becomes chronic and how chronic pain information is stored and processed in the brain. This new knowledge will lead to advances in diagnostics, therapeutics and management for those suffering with neuropathic pain. The understanding of these mechanisms can lead to the development of a new generation of drugs aimed at selectively targeting and treating chronic pain and repairing damaged nervous function.

By showing altered brain function and genetic components in chronic pain, this research will help in reducing the severe stigmatization of people suffering from chronic pain. In addition, patients with neuropathic pain often suffer from depression secondarily and any improved pain control can improve mental health overall.

In a broader sense, the molecular mechanisms elucidated in this research are relevant in the study of other Central Nervous System disorders such Alzheimer’s disease, Parkinson’s disease and neuroinflammatory disease.

 

Findings
Imagine being unable to wear a shirt or to allow a gentle breeze to blow across your face because these harmless stimuli cause you excruciating pain. This is the type of situation that the millions of individuals worldwide try to live with every day. This is neuropathic pain -- the most debilitating of all pain states. Neuropathic pain often arises from injury to a nerve in the body or may complicate a wide variety of conditions, such as cancer, AIDS and diabetes. This type of pain is nearly always resistant to known treatments, even strong narcotics. This team has made a major step forward by establishing that malfunctioning in the spinal cord causes neuropathic pain. They discovered that a type of cell in the spinal cord – the microglia – previously thought to be only involved in responses to viral or bacterial infections become activated after injury to nerves in the body. These activated microglia emit chemical signals that stimulate nerve cells in spinal cord pain pathways and cause them to send messages to the brain even if the skin is only harmlessly stimulated. The brain then interprets these messages as pain not harmless stimulation.

November 16, 2008
NeuroScience Canada researchers discover novel therapy for chronic pain

Impact
The team discovered cell types, molecules and genes involved in neuropathic pain. This new knowledge will lead to a range of advances not only in treatment but also in the diagnosis of neuropathic pain in those suffering.

Publications

September 27, 2007 Molecular Pain - 
Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain
November 15, 2006 Pain - 
Spinal microglia and neuropathic pain in young rats
December 15, 2005 Nature - 
BDNF from Microglia Causes the Shift in Neuronal Anion Gradient Underlying Neuropathic Pain