New pain target for bacterial infections

February 10, 2014
Bacterial components (LPS) activate the cation channel TRPA1 in sensory neurons, causing acute pain and inflammation. Credit: Karel Talavera

Components in the outer wall of bacteria directly activate pain sensors, triggering immediate pain and inflammatory responses. This finding by a multinational team of researchers led by Professor Karel Talavera (KU Leuven, Belgium) and Professor Félix Viana (Institute of Neuroscience, Spain) sheds new light on pain associated with bacterial infections and reveals a new target for drugs designed to treat them.

Bacterial infections are a global health problem and their treatment remains a major challenge to modern medicine. Infections of Gram-negative bacteria, in particular, are a major cause of human diseases, such as pneumonia, meningitis, gastroenteritis and gonorrhea.

Part of Gram-negative bacteria's danger lies in certain disease-causing components in the bacteria's outer wall. The most significant, say the researchers, is lipopolysaccharide (LPS). In bacterial infections, LPS fragments from damaged bits of the bacterial walls are released locally, triggering an immune response.

When they come in contact with specialised TLR4 receptors at the surface of 'sentinel' , chemicals are released that recruit other immune cells, inducing swelling, tissue injury and eventual lyses and clearance of the bacteria.

But our immune system is unable to respond quickly enough to the presence of LPS, and fast reactions to this molecule, such as acute , inflammation and , remained unexplained until now.

Toothache

The study, published in the 20 January issue of Nature Communications, uncovers, on the molecular level, how LPS causes these symptoms. The researchers found that LPS insert in the membrane surrounding , inducing a mechanical deformation that is then sensed by TRPA1 proteins. This leads to activation of TRPA1 within a matter of seconds, the influx of positively-charged ions into the nerves and the firing of electric signals that are interpreted as pain by our central nervous system.

In addition, the influx of calcium ions through TRPA1 induces the release of factors that produce dilation of the blood vessels and tissue inflammation.

The study is the culmination of a five-year probe by lead author Victor M. Meseguer (UC Berkeley) that started in a dentist's office. Inquiring into the cause of his toothache, he was told it was a but that the underlying molecular mechanisms were not yet known. Today, he and his co-authors are able to show that his tooth pain was caused by bacterial LPS targeting TRPA1.

TRPA1 proteins are already known to be a detector of multiple harmful compounds contained in smoke, mustard, wasabi and tobacco. We can now add bacterial LPS to that list, say the researchers.

"The identification of TRPA1 as a molecular determinant of direct LPS effects on pain-sensing neurons offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment," said senior author Karel Talavera.

More information: The paper "TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins" by Victor Meseguer et al. is available on the website of Nature Communications: www.nature.com/ncomms/2014/140120/ncomms4125/full/ncomms4125.html

Related Stories

Team finds molecule that triggers septic shock

September 12, 2013

The body's immune system is set up much like a home security system; it has sensors on the outside of cells that act like motion detectors—floodlights—that click on when there's an intruder rustling in the bushes, bacteria ...

Detecting sickness by smell

January 23, 2014

Humans are able to smell sickness in someone whose immune system is highly active within just a few hours of exposure to a toxin, according to new research published in Psychological Science, a journal of the Association ...

Powerful bacterial immune response defined by new study

February 6, 2014

T-cells, the elite guard of the immune system in humans and other mammals, ignore normal biologic protocol and swing into high gear when attacked by certain fast-moving bacteria, reports a team of researchers led by a UC ...

Recommended for you

Crystal clear images uncover secrets of hormone receptors

July 31, 2015

Many hormones and neurotransmitters work by binding to receptors on a cell's exterior surface. This activates receptors causing them to twist, turn and spark chemical reactions inside cells. NIH scientists used atomic level ...

A cheaper, high-performance prosthetic knee

July 30, 2015

In the last two decades, prosthetic limb technology has grown by leaps and bounds. Today, the most advanced prostheses incorporate microprocessors that work with onboard gyroscopes, accelerometers, and hydraulics to enable ...

Flow means 'go' for proper lymph system development

July 27, 2015

The lymphatic system provides a slow flow of fluid from our organs and tissues into the bloodstream. It returns fluid and proteins that leak from blood vessels, provides passage for immune and inflammatory cells from the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.