The research provides novel insights into the molecular basis for altered firing of pain signaling neurons in primary erythromelalgia, according to Stephen Waxman, M.D., senior author of the study, chair of the Department of Neurology and director of the West Haven Veterans Administration Rehabilitation Research Center.

DNA samples were studied from a family with 36 members, of which 17 exhibit symptoms typical of erythromelalgia--attacks of intense burning pain of the hands and feet triggered most commonly by heat and moderate exercise. There is currently no effective treatment for erythromelalgia.

All 17 affected members of this family carried a mutation in the gene for sodium channel Nav1.7, one of the nine sodium channels. Nav1.7 is abundantly and preferentially present in small-diameter nerve fibers and free nerve endings within the peripheral nervous system and is associated with pain transmission.

Previous studies linked primary erythromelalgia to two mutations in the gene coding for sodium channel Nav1.7. This study describes a third mutation in Nav1.7 and is evidence that mutant Nav1.7 predisposes its pain sensing neurons to become hyperexcitable and fire rapid bursts of signals at lower than normal stimulation. Hyperexcitability has long been considered a hallmark of painful neuropathies.

Identification of mutations in a specific sodium channel in people with primary erythromelalgia suggests the possibility of rational therapies that target the affected channel. Also, because other pain syndromes, including acquired disorders, involve altered sodium channel function, erythromelalgia may emerge as a model disease that holds more general lessons about the molecular neurobiology of chronic pain.

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In a companion study, also published in tomorrow's issue of The New England Journal of Medicine, scientists led by Dr. Ming Tsao and Dr. Frances Shepherd at Princess Margaret Hospital assessed tumour biopsies from some of the patients on the study. They looked for gene mutations, gene copy number, and the expression of the epidermal growth factor receptor protein in the cancer cells. Their findings suggest that molecular testing is not necessary to identify appropriate patients for treatment with erlotinib.

Lung cancer is one of the most common forms of cancer worldwide, and it is the leading cause of death from cancer in North America. Non-small cell lung cancer is the most common type of lung cancer, accounting for almost 80 per cent of all cases. An estimated 22,200 Canadians will be diagnosed with lung cancer this year, and 19,000 will die of the disease.

The lung cancer clinical study was coordinated by the National Cancer Institute of Canada Clinical Trials Group, which is funded by the Canadian Cancer Society and based at Queen's University in Kingston, Ontario. It was also funded by OSI Pharmaceuticals Inc.

Princess Margaret Hospital and its research arm, Ontario Cancer Institute, have achieved an international reputation as global leaders in the fight against cancer. Princess Margaret Hospital is a member of the University Health Network, which also includes Toronto General Hospital and Toronto Western Hospital. All three are teaching hospitals affiliated with the University of Toronto.

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