Yale Bulletin and Calendar

October 8, 2004|Volume 33, Number 6

Physical basis of hereditary
pain syndrome identified

Yale researchers offer the first explanation of the physiological basis for the inherited, chronic pain syndrome known as erythromelalgia in a Sept. 24 article in the Journal of Neuroscience.

Erythromelalgia has largely remained an obscure disease with unknown cause until the advent of the genomics era. The article describes the physiological abnormality which leads to erythromelalgia, a condition characterized by intermittent intense burning pain in the extremities and symptoms of redness, heat, pain and swelling.

Using the catalog of human genes, recent studies linked erythromelalgia to two mutations in SCN9A, a gene that codes for a voltage-gated sodium channel of the subtype Nav1.7. Voltage-gated sodium channels are present along the length of nerve fibers where they serve as molecular batteries in generating and transmitting nerve signals.

A research team led by Dr. Stephen Waxman, chair and professor of neurology and director of the Veterans Affairs Rehabilitation Research Center in West Haven, showed how abnormal function of Nav1.7 channels, as a result of these mutations, leads to inappropriate, spontaneous firing of pain-signaling nerve cells.

Waxman and his colleagues Sulayman Dib-Hajj and Theodore Cummins previously discovered the role of Nav1.7 in generating impulses within pain-signalling nerve cells. This study set out to examine the contribution of mutations in Nav1.7 to the pathophysiology of erythromelalgia. They recorded electrical currents from cells with mutant Nav1.7 and compared them with cells expressing normal Nav1.7.

The investigators observed that mutant Nav1.7 channels displayed altered behavior, which can cause neurons to turn on more easily and poise them to fire signals at higher than normal rates. Such a behavior is consistent with numerous findings linking hyper-excitability of pain-signaling nerve cells to pain syndromes.

"We are excited about these findings because they may teach us about the molecular basis for pain associated with inflammation and nerve injury," Waxman says. "Hopefully the findings will contribute to the development of new therapies for erythromelalgia."

T H I SW E E K ' SS T O R I E S

Andrew Hamilton named Yale Provost

Yale rated tops in Fulbright grant winners

Program marks 35 years of helping youngsters succeed in school

Interest in community building, world of theater . . .

Story of a 'solitary yellow in a white world' is tale of hope, says Koh

Yale Employee Day at the Bowl will feature free giveaways

This year's Divinity School Convocation features concert . . .

Event explores the future of Judaism

Design icon William Morris is focus of new exhibit

Event celebrates law professor's scholarly work

Physical basis of hereditary pain syndrome identified

Study reveals crucial role of lipid in synaptic transmission

Model shows most recent common ancestor of today's humans . . .

Researchers discover VEGF molecule plays key role in asthma

Dr. Martin Gordon wins medical school honor

Engineer T.P. Ma recognized for his scientific accomplishments

Martin Saunders is cited by the American Chemical Society

Sherwin receives award for efforts in diabetes treatment, research

Memorial service for Dr. Frederick Redlich

Campus Notes