Featured Research

from universities, journals, and other organizations

Origin Of Inherited Pain Disorder Pinpointed

Date:
December 8, 2006
Source:
Cell Press
Summary:
The genetic basis for a rare inherited disorder that causes severe burning pain with no warning has been pinpointed by researchers. They found that paroxysmal extreme pain disorder (PEPD) is caused by specific mutations in porelike sodium channels in peripheral nerve cells -- a discovery that they said emphasizes the role of such channel disorders in inflammatory pain. Such findings of abnormal function in disease also provide insights into the normal function of such channels, they said.

The genetic basis for a rare inherited disorder that causes severe burning pain with no warning has been pinpointed by researchers. They found that paroxysmal extreme pain disorder (PEPD) is caused by specific mutations in porelike sodium channels in peripheral nerve cells--a discovery that they said emphasizes the role of such channel disorders in inflammatory pain. Such findings of abnormal function in disease also provide insights into the normal function of such channels, they said.

R. Mark Gardiner, of University College London, and his colleagues published their findings in the December 7, 2006, issue of the journal Neuron, published by Cell Press.

So-called "voltage-gated sodium channels" are central to the neuron's ability to propagate a nerve impulse. In response to voltage changes in a nerve cell caused by a nerve impulse, these channels snap open, allowing sodium to flow across the cell membrane, further propagating the nerve impulse. Rapid, precise activation and inactivation is key to their normal operation.

In their studies, the researchers sought to understand the basis of PEPD, which is characterized by abrupt paroxysms of pain in the rectum, eye, and jaw. They first performed a detailed genetic comparison of affected and unaffected members of one large family that showed inheritance of the disease. That analysis revealed that mutations that compromise the gene for a component of one particular sodium channel, called SCN9A, were the likely culprit. Further analysis of the gene in 11 affected families and two sporadic cases, indeed, revealed that mutations in SCN9A are responsible for the disease in at least two-thirds of PEPD cases.

Analysis of these mutations revealed that they all disrupted the ability of the sodium channel to rapidly snap shut, prolonging activation of the peripheral nerves in which the channels functioned. What's more, the researchers found, the drug carbamazepine--known to be effective in PEPD--acts to correct this abnormality in cultures of neurons.

The researchers also compared PEPD with another inherited pain disorder, primary erythermalgia (PE) that is not alleviated by carbamazepine. PE is also caused by mutations in SCN9A and is characterized by pain in the extremities triggered by exercise or temperature change. In contrast to PEPD, which is caused by mutations that disrupt inactivation the sodium channel, PE arises from mutations that lower its activation threshold.

The researchers concluded that their findings "further emphasize the critical role of [this sodium channel] in human inflammatory pain and explain the differential drug sensitivity of PEPD and PE."

The researchers include Caroline R. Fertleman, Keith A. Parker, Sarah Moffatt, Frances V. Elmslie, R. Mark Gardiner, and Michele Rees of Royal Free and University College Medical School, University College London in London, UK; Mark D. Baker, Bjarke Abrahamsen, and John N. Wood of University College London in London, UK; Johan Ostman of Queen Mary's School of Medicine and Dentistry in London, UK; Norbert Klugbauer of Albert-Ludwigs-Universitδt Freiburg in Freiburg, Germany.

This work was funded by The Wellcome Trust (Research Training Fellowship, C.R.F.) and MRC (UK).

Fertleman et al.: "SCN9A Mutations in Paroxysmal Extreme Pain Disorder: Allelic Variants Underlie Distinct Channel Defects and Phenotypes." Publishing in Neuron 52, 767--774, December 7, 2006 DOI 10.1016/j.neuron.2006.10.006. http://www.neuron.org


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Origin Of Inherited Pain Disorder Pinpointed." ScienceDaily. ScienceDaily, 8 December 2006. <www.sciencedaily.com/releases/2006/12/061207160634.htm>.
Cell Press. (2006, December 8). Origin Of Inherited Pain Disorder Pinpointed. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2006/12/061207160634.htm
Cell Press. "Origin Of Inherited Pain Disorder Pinpointed." ScienceDaily. www.sciencedaily.com/releases/2006/12/061207160634.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) — An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) — Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) — It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) — According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins