A team of researchers led by Université Laval and The Hospital for Sick Children has discovered a protein that plays a major role in neuropathic pain.
This discovery, published in the 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 Michael Salter, co-principal investigator, at The Hospital for Sick Children and University of Toronto ( U of T ). " 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 Yves De Koninck, co-principal investigator, at Université Laval. " 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 Salter." 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.

Source: University of Toronto, 2005


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