Navigation Links
Shingles symptoms may be caused by neuronal short circuit

The pain and itching associated with shingles and herpes may be due to the virus causing a "short circuit" in the nerve cells that reach the skin, Princeton researchers have found.

This short circuit appears to cause repetitive, synchronized firing of nerve cells, the researchers reported in the journal Proceedings of the National Academy of Sciences. This cyclical firing may be the cause of the persistent itching and pain that are symptoms of oral and genital herpes as well as shingles and chicken pox, according to the researchers.

These diseases are all caused by viruses of the herpes family. Understanding how these viruses cause discomfort could lead to better strategies for treating symptoms.

The team studied what happens when a herpes virus infects neurons. For research purposes the investigators used a member of the herpes family called pseudorabies virus. Previous research indicated that these viruses can drill tiny holes in neurons, which pass messages in the form of electrical signals along long conduits known as axons.

The researchers' findings indicate that electrical current can leak through these holes, or fusion pores, and spread to nearby neurons that were similarly damaged, causing the neurons to fire all at once rather than as needed. The pores were likely created for the purpose of infecting new cells, the researchers said.

The investigators observed the cyclical firing of neurons in a region called the submandibular ganglia between the salivary glands and the brain in mice using a technique called 2-photon microscopy and dyes that flash brightly when neurons fire.

The team found that two viral proteins appear to work together to cause the simultaneous firing, according to Andra Granstedt, who received her Ph.D. in molecular biology at Princeton in 2013 and is the first author on the article. The team was led by Lynn Enquist, Princeton's Henry L. Hillman Professor in Molecular Biology and a member of the Princeton Neuroscience Institute.

The first of these two proteins is called glycoprotein B, a fusion protein that drills the holes in the axon wall. A second protein, called Us9, acts as a shuttle that sends glycoprotein B into axons, according to the researchers. "The localization of glycoprotein B is crucial," Granstedt said. "If glycoprotein B is present but not in the axons, the synchronized flashing won't happen."

The researchers succeeded in stopping the short circuit from occurring in engineered viruses that lacked the gene for either glycoprotein B or Us9. Such genetically altered viruses are important as research tools, Enquist said.

Finding a way to block the activity of the proteins could be a useful strategy for treating the pain and itching associated with herpes viral diseases, Enquist said. "If you could block fusion pore formation, you could stop the generation of the signal that is causing pain and discomfort," he said.

Granstedt conducted the experiments with Jens-Bernhard Bosse, a postdoctoral research associate in molecular biology. Assistance with 2-photon microscopy was provided by Stephan Thiberge, director of the Bezos Center for Neural Circuit Dynamics at the Princeton Neuroscience Institute.

The team previously observed the synchronized firing in laboratory-grown neurons (PLoS Pathogens, 2009), but the new study expands on the previous work by observing the process in live mice and including the contribution of Us9, Granstedt said.

Shingles, which is caused by the virus herpes zoster and results in a painful rash, will afflict almost one out of three people in the United States over their lifetime. Genital herpes, which is caused by herpes simplex virus-2, affects about one out of six people ages 14 to 49 years in the United States, according the Centers for Disease Control and Prevention.


Contact: Catherine Zandonella
Princeton University

Related medicine news :

1. Shingles Vaccine Safe, Underutilized, Study Says
2. Treatment with anti-TNFs can increase the risk of shingles by up to 75 percent
3. Shingles Not Linked to Increased Cancer Risk, Study States
4. No increased risk of cancer for people with shingles
5. Doctors Encourage Treatment for Shingles to Be Started When the Pain Kicks in – VyGone Introduces Shingles Vaccine
6. Study suggests link between untreated depression and response to shingles vaccine
7. Untreated Depression May Cut Shingles Vaccine Effectiveness
8. UCLA study suggests link between untreated depression, response to shingles vaccine
9. Shingles Treatment
10. How “How To Cure Shingles” Helps People Get Rid Of Shingles Quickly – Health Review Center
11. Newer Rheumatoid Arthritis Drugs Dont Seem to Increase Risk of Shingles
Post Your Comments:
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet ... product that was developed to enhance the health of felines. The formula is all-natural ... two main herbs in the PawPaws Cat Kidney Support Supplement Soft Chews ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... and applications at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the Hynes ... important health care topics including advance care planning, healthcare costs and patient and ...
(Date:6/25/2016)... ... June 25, 2016 , ... "With 30 hand-drawn hand gesture animations, FCPX ... Austin - CEO of Pixel Film Studios. , ProHand Cartoon’s package transforms over ... Cut Pro X . Simply select a ProHand generator and drag it above media ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... recover from injury. Recently, he has implemented orthobiologic procedures as a method for ... is one of the first doctors to perform the treatment. Orthobiologics are substances ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... A recent ... that most people are unfamiliar with. The article goes on to state that individuals ... also many of these less common operations such as calf and cheek reduction. The ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... -- Research and Markets has announced ... Applications, Technologies, Forecasts" report to their offering. ... Smart Skin, Structural Health Monitoring, Composite Smart Structures, ... involves electronic and/or electrical components and circuits that ... such as vehicle bodies or conformally placed upon ...
(Date:6/24/2016)... According to a new market ... Needles, Safety Pen Needles), Needle Length (4mm, 5mm, 6mm, ... of Purchase (Retail, Non-Retail) - Trends & Global Forecasts ... market for the forecast period of 2016 to 2021. ... by 2021 from USD 1.65 Billion in 2016, growing ...
(Date:6/23/2016)... 23, 2016 Research and Markets has ... - Forecast to 2022" report to their offering. ... for the patients with kidney failure, it replaces the function ... the patient,s blood and thus the treatment helps to keep ... in balance. Increasing number of ESRD patients ...
Breaking Medicine Technology: