Nerve pain: Understanding and Diagnosing an Inherited Pain Syndrome

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Understanding and Diagnosing an Inherited Pain Syndrome

13 Jul 2005 Medical News Today

Yale School of Medicine researchers report the first demonstration

that a single mutation in a human sodium channel gene can trigger

pain in people with an inherited pain syndrome known as primary

erythromelalgia, according to a study published this month in the

journal Brain.

The research provides novel insights into the molecular basis for

altered firing of pain signaling neurons in primary erythromelalgia,

according to 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.

Co-authors of the study include Sulayman Dib-Hajj, Rush,

Theodore Cummins, Fuki Hisama, Novella, Lynda Tyrrell and

Marshall. Funding for the research was provided in part by the

Erythromelalgia Association.

Brain Advance Access (June 15, 2005)

http://www.yale.edu/opa