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Gene Mutation Causing Hyper-excitable Nerve Cells Explains Many Cases of 'Unexplained Pain' - Yale

  [ 16 votes ]   [ Discuss This Article ]
www.ProHealth.com • June 25, 2011


Mutations in the SCN9A gene (found in a third of ‘unexplained’ neuropathic pain patients) cause nerve cells to be hyper-excitable, thus leading to degeneration of the nerve fibers.

Roughly 20 million people in the US suffer from peripheral neuropathy, marked by the degeneration of nerves and in some cases severe chronic pain. There is no good treatment for the disorder and no apparent cause for the destruction in a third of cases.

But now an international team of scientists headed by researchers from Yale University and the Veterans Affairs Medical Center in New Haven, Connecticut, and the University Maastricht in the Netherlands have linked mutations of a single gene to 30% of cases of unexplained neuropathy.

The findings, published online June 22 in the Annals of Neurology, could lead to desperately needed pain treatments for many victims of this debilitating disorder.

"For millions of people, the origin of this intense pain has been a frustrating mystery," says Yale neurologist Stephen Waxman, MD, a co-author of the study. "All of us were surprised to find that these mutations occur in so many patients with neuropathy with unknown cause."

The study focused on mutations of a single gene - SCNA9 - which is expressed in sensory nerve fibers.

• Waxman's group had discovered that mutations in this gene's product - the protein sodium channel Nav1.7 - cause a rare disorder called "Man on Fire Syndrome," characterized by excruciating and unrelenting pain.

• Colleagues in the Netherlands carefully scrutinized neuropathy patients to rule out all known causes of the neuropathy, such as diabetes, alcoholism, metabolic disorders and exposure to toxins.

• Researchers then did a genetic analysis of 28 patients with neuropathy with no known cause. They found that:

- 30% of these subjects had mutations in the SCN9A gene.

- And the mutations cause nerve cells to become hyperactive, a change they believe eventually leads to degeneration of nerve fibers.

"These findings will help us as clinicians to a better understanding of our patients with small fiber neuropathy and could ideally have implications for the development of future specific therapies," says University Maastrict co-author Catharina G. Faber, MD, PhD.

The research was funded by the Department of Veterans Affairs, The Erythromelalgia Association (USA), and the Profileringsfonds of University of Maastricht, The Netherlands.

Source: Yale University news release, Jun 22, 2011




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