Researchers identify key protein involved in neuropathic pain

December 14, 2005

A team of researchers led by Université Laval and The Hospital for Sick Children (SickKids) has discovered a protein that plays a major role in neuropathic pain. This discovery, published in the December 16 issue of Nature, paves the way for the development of new diagnostics and treatments for chronic pain.

Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Many people suffering from neuropathic pain appear normal, but are in agony experiencing lightning-like pain known as allodynia.

This type of pain can alter perception to a point where previously innocuous or even pleasurable stimuli applied to the skin or tissues become extremely painful. It may be experienced after nerve injury or from diseases that affect peripheral nerve function such as diabetes, shingles, or cancer.

After a peripheral nerve injury there is a biophysical change in spinal cord cells called microglia. Microglia are typically considered to be immune cells in the nervous system, but have now been proven to be involved in neuropathic pain.

"We knew that microglia had to communicate with nerve cells in the pain-processing network in the spinal cord. However the mechanism for this communication was not known," said Dr. Michael Salter, co-principal investigator, senior scientist at SickKids, professor of Physiology at the University of Toronto (U of T), and director of the U of T Centre for the Study of Pain. "We discovered that the microglia talk to the nerves cells by releasing Brain-Derived Neurotropic Factor (BDNF)."

When BDNF was injected into the spinal cords of normal mice it resulted in allodynia. When the team made manipulations to block or intercept BDNF signaling from the microglia the in nerve-injured mice the allodynia was reversed.

"We established that the microglia cause chloride ions to increase inside the nerve cells and that BDNF is the mystery mediator," said Dr. Yves De Koninck, co-principal investigator, professor, Department of Psychiatry, Université Laval and director of the Division of Cellular Neurobiology at the Centre de recherche Université Laval Robert-Giffard. "Thus, not only did we discover that BDNF is the chemical mediator, but we also determined how BDNF works."

By a still unknown mechanism, nerve injury results in activation of P2X4 receptors on the microglia, which causes the release of BDNF. BDNF then disrupts inhibition in the spinal cord, which causes spinal relay neurons to send an abnormal signal to pain-processing neural networks in the brain, ultimately causing the experience of aberrant pain.

The research team hopes that this new information on neuropathic pain can be applied to diagnostics. "Effective pain diagnosis is nearly as big a challenge as developing effective pain therapeutics," added Dr. Salter, also Canada Research Chair in Neuroplasticity and Pain. "The gold standard for diagnosing neuropathic pain is history and physical examination. But many people want objective proof that something is pathophysiologically different. We are hoping to develop a probe that can measure the response of microglia in people with peripheral nerve injury."

The team is also looking for ways to devise new kinds of therapeutics, as there is not presently any effective treatment for neuropathic pain.

"This is an important discovery for the millions of Canadians who suffer from debilitating chronic pain that cannot currently be treated. The cost to society is equally devastating and is estimated in the billions of dollars annually," said the Honourable Michael H. Wilson, chair of NeuroScience Canada, one of the funders of this research through the Brain Repair Program, which includes $1.5 million to the team led by Dr. Michael Salter. NeuroScience Canada's funding partners on the team grant led by Dr. Salter include the Canadian Institutes of Health Research and the Ontario Neurotrauma Foundation.

"With the work of Drs. Salter and De Koninck, we can now focus the research on developing drugs that will target the class of cells responsible for chronic pain. This represents an important shift that could soon provide patients with effective treatments and allow them to be active again in our society," added Mr. Wilson.
-end-
Other members of the research team include co-lead authors Dr. Simon Beggs of SickKids and Dr. Jeffrey Coull of McGill University, Dominic Boudreau, Dominick Bovin and Dr. Claude Gravel of Université Laval, Drs. Makoto Tsuda and Kazuhide Inoue of Kyushu University, Japan.

This research was supported by the Canada Research Chairs Program, the Canadian Institutes of Health Research, Fonds de la recherche en santé du Québec, Neuroscience Canada and SickKids Foundation.

Located in Quebec's historic capital city, Université Laval is one of Canada's leading research universities, ranking 6th among the country's 93 university-level institutions in terms of research funding, with more than $250 million devoted to research last year.

The Hospital for Sick Children, affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. Its mission is to provide the best in family-centred, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health. For more information, please visit www.sickkids.ca.

For more information, please contact:
Chelsea Gay, Public Affairs
The Hospital for Sick Children
(416) 813 5045
chelsea.gay@sickkids.ca

or

Jean-François Huppé, Direction des affaires publiques
Université Laval
(418) 656-7785
jean-francois.huppe@dap.ulaval.ca

University of Toronto

Related Chronic Pain Articles from Brightsurf:

Researchers are developing potential treatment for chronic pain
Researchers from the University of Copenhagen have developed a new way to treat chronic pain which has been tested in mice.

Molecular link between chronic pain and depression revealed
Researchers at Hokkaido University have identified the brain mechanism linking chronic pain and depression in rats.

How chikungunya virus may cause chronic joint pain
A new method for permanently marking cells infected with chikungunya virus could reveal how the virus continues to cause joint pain for months to years after the initial infection, according to a study published Aug.

Gastroesophageal reflux associated with chronic pain in temporomandibular joint
Gastroesophageal reflux (GERD) is associated with chronic, painful temporomandibular disorder -- pain in the temporomandibular joint -- and anxiety and poor sleep contribute to this association, according to a study in CMAJ.

One step closer to chronic pain relief
While effective drugs against chronic pain are not just around the corner, researchers from Aarhus University, Denmark, have succeeded in identifying a protein as a future potential target for medicinal drugs.

Gut bacteria associated with chronic pain for first time
In a paper published today in the journal Pain, a Montreal-based research team has shown, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia.

Nearly 5.4 million cancer survivors suffer chronic pain
A new report finds about one in three cancer survivors (34.6%) reported having chronic pain, representing nearly 5.4 million cancer survivors in the United States.

New opioid speeds up recovery without increasing pain sensitivity or risk of chronic pain
A new type of non-addictive opioid developed by researchers at Tulane University and the Southeast Louisiana Veterans Health Care System accelerates recovery time from pain compared to morphine without increasing pain sensitivity, according to a new study published in the Journal of Neuroinflammation.

New target for chronic pain relief confirmed by scientists
A research group at Hiroshima University observed a potential new target for chronic pain treatment.

Menopause symptoms nearly double the risk of chronic pain
In addition to the other health conditions affected by estrogen, it has also been shown to affect pain sensitivity.

Read More: Chronic Pain News and Chronic Pain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.