(Press-News.org) Anyone who has suffered through sleepless nights due to uncontrollable itching knows that not all itching is the same. New research at Washington University School of Medicine in St. Louis explains why.
Working in mice, the scientists have shown that chronic itching, which can occur in many medical conditions, from eczema and psoriasis to kidney failure and liver disease, is different from the fleeting urge to scratch a mosquito bite.
That's because chronic itching appears to incorporate more than just the nerve cells, or neurons, that normally transmit itch signals. The researchers found that in chronic itching, neurons that send itch signals also co-opt pain neurons to intensify the itch sensation.
The new discovery may lead to more effective treatments for chronic itching that target activity in neurons involved in both pain and itch. The research is reported online Oct. 15 in The Journal of Clinical Investigation and will appear in the November print issue.
"In normal itching, there's a fixed pathway that transmits the itch signal," said senior investigator Zhou-Feng Chen, PhD, who directs Washington University's Center for the Study of Itch. "But with chronic itching, many neurons can be turned into itch neurons, including those that typically transmit pain signals. That helps explain why chronic itching can be so excruciating."
Chen, a professor of anesthesiology, and his colleagues generated mice in which a protein called BRAF always is active and continually sends signals inside itch neurons. The BRAF gene and the protein it makes are involved in the body's pain response, but scientists didn't know whether the gene also played a role in itch.
"We thought the animals might be prone to feeling pain rather than itching," Chen explained. "To our great surprise, the mice scratched spontaneously. At first, we didn't know why they were scratching, but it turns out we developed a mouse model of chronic itch."
Further studies discovered that the BRAF protein could turn on many itch genes, and they showed similar changes of gene expression in mice with chronic itch induced by dry skin and in mice with allergic contact dermatitis, two of the skin conditions that frequently cause people to scratch incessantly.
The findings suggest that targeting proteins in the BRAF pathway may open new avenues for treating chronic itch, a condition in which few therapies are effective. One possibility includes using drugs that are prescribed to treat pain.
"Certain drugs are used to inhibit some of the same targets in patients with chronic pain, and those medications also may quiet down itch," Chen said.
In earlier studies, Chen identified gastrin-releasing peptide (GRP), a substance that carries itch signals to a gene called GRPR (gastrin-releasing peptide receptor) in the spinal cord. In the new study, GRP and GRPR activity was doubled in the genetically altered mice, which could account for some of the increase in the intensity of itching. But other genes that normally are activated by pain also were turned on in the itch pathway, further intensifying the itch sensation.
Surprisingly, however, the mice had a normal response to pain, indicating that the pain and itch pathways are very different.
AUDIO:
There are several medical conditions, from dry skin to psoriasis, that can cause uncontrollable itching that doesn't go away. Now researchers at Washington University School of Medicine in St. Louis...
Click here for more information.
Unlike scratching a mosquito bite, which usually is only a temporary sensation, chronic itch can persist much longer, according to Chen, also a professor of psychiatry and of developmental biology. His team found that the mice in this study not only scratched spontaneously but also had more severe responses when exposed to substances that normally would induce acute itching.
"In people, chronic itching can last for weeks, months or even years," Chen said. "These mice are helping us to understand the pathways that can be involved in transmitting itch signals and the many contributors to chronic itching. There are many pathways leading from BRAF, and all of these could be potential targets for anti-itch therapies."
INFORMATION:
Funding for this research comes from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) the National Eye Institute (NEI), and a training grant from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH).
NIH grant numbers R01 AR056318-01A.
Zhau ZQ, Huo FQ, Jeffry J, Hampton L, Demehri S, Kim S, Liu XY, Barry DM, Wan L, Liu ZC, Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey JF, Zhong J, Chen ZF. Chronic itch development in sensory neurons requires BRAF signaling pathways. The Journal of Clinical Investigation vol. 123 (11), November 2013, published online Oct.15, 2013. http://www.jci.org
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Scientists unravel mechanisms in chronic itching
2013-10-15
ELSE PRESS RELEASES FROM THIS DATE:
Pain of poverty sticks, despite support of neighbors or spouses
2013-10-15
Being married or having the support of neighbors to rely on does little to alleviate the symptoms of depression associated with economic hardship often experienced by poor mothers. With these findings, published in Springer's American Journal of Community Psychology, Sharon Kingston of Dickinson College in the US challenges the growing perception that marriage and other forms of interpersonal support can buffer the negative effects of poverty.
In studying 1,957 mothers from 80 neighborhoods in Chicago, Kingston examined the combined effect of economic adversity and having ...
This week in Molecular Biology and Evolution
2013-10-15
On the road to our modern human lineage, scientists speculate there were many twist and turns, evolutionary dead ends, and population bottlenecks along the way. But how large were population sizes of common ancestors of the great apes and humans, and does the genetic analysis support the prevailing views of a great bottleneck in primate evolution?
Using inferred evolutionary rates of more than 1400 genes and ancestral generation times, Professor Carlos Schrago and colleagues trace population histories backwards across evolutionary time to estimate population sizes for ...
New evidence on lightning strikes: Mountains a lot less stable than we think
2013-10-15
Lightning strikes causing rocks to explode have for the first time been shown to play a huge role in shaping mountain landscapes in southern Africa, debunking previous assumptions that angular rock formations were necessarily caused by cold temperatures, and proving that mountains are a lot less stable than we think.
In a world where mountains are crucial to food security and water supply, this has vast implications, especially in the context of climate change.
Professors Jasper Knight and Stefan Grab from the School of Geography, Archaeology and Environmental Studies ...
Recovery from childhood ADHD may depend on the pattern of brain development
2013-10-15
Philadelphia, PA, October 15, 2013 – Some people grow out of their childhood attention-deficit/hyperactivity disorder (ADHD) and some don't. In fact, around 50% of individuals diagnosed as children continue to suffer from ADHD as adults.
Researchers are trying to understand the reasons why, and relatedly, whether there are any differences that distinguish the two groups. Gender, ethnicity, socioeconomic class, and symptom severity have already been ruled out as potentials. So, perhaps there is a distinguishing variable in the brain? Dr. Philip Shaw at the National Human ...
Halloween candy spooks aging digestive systems! Research in fruit flies helps explain why
2013-10-15
Have you ever wondered why young children can eat bags of Halloween candy and feel fine the next day – compared to adults who experience all sorts of agony following the same junk food binge? Evolution and a gene called Foxo may be to blame. Working in fruit flies, scientists at the Buck Institute have identified a mechanism that helps the flies adapt to changes in diet when they're young; they've discovered that same mechanism gets misregulated as the flies age, disrupting metabolic homeostasis, or balance.
In a study appearing in Cell Reports, researchers focus on ...
UT Southwestern reports promising new approach to drug-resistant infections
2013-10-15
DALLAS – Oct. 15, 2013 – A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to health care settings, UT Southwestern Medical Center researchers report.
The technology and new approach offer potential promise against the growing problem of antibiotic resistance, the researchers said.
The pathogen (germ) – called Acinetobacter – can cause infections from pneumonia to serious blood or wound infections, posing greater risk to people with weakened immune systems, ...
New 3-D method used to grow miniature pancreas
2013-10-15
An international team of researchers from the University of Copenhagen have successfully developed an innovative 3D method to grow miniature pancreas from progenitor cells. The future goal is to use this model to help in the fight against diabetes. The research results has just been published in the scientific journal Development.
Professor Anne Grapin-Botton and her team at the Danish Stem Cell Centre have developed a three-dimensional culture method which enables the efficient expansion of pancreatic cells. The new method allows the cell material from mice to grow ...
The musical ages of modern man: How our taste in music changes over a lifetime
2013-10-15
The explosion in music consumption over the last century has made 'what you listen to' an important personality construct – as well as the root of many social and cultural tribes – and, for many people, their self-perception is closely associated with musical preference. We would perhaps be reluctant to admit that our taste in music alters - softens even - as we get older.
Now, a new study suggests that - while our engagement with it may decline - music stays important to us as we get older, but the music we like adapts to the particular 'life challenges' we face at different ...
Method of recording brain activity could lead to mind-reading devices, Stanford scientists say
2013-10-15
STANFORD, Calif. — A brain region activated when people are asked to perform mathematical calculations in an experimental setting is similarly activated when they use numbers — or even imprecise quantitative terms, such as "more than"— in everyday conversation, according to a study by Stanford University School of Medicine scientists.
Using a novel method, the researchers collected the first solid evidence that the pattern of brain activity seen in someone performing a mathematical exercise under experimentally controlled conditions is very similar to that observed when ...
Rice scientists create a super antioxidant
2013-10-15
Scientists at Rice University are enhancing the natural antioxidant properties of an element found in a car's catalytic converter to make it useful for medical applications.
Rice chemist Vicki Colvin led a team that created small, uniform spheres of cerium oxide and gave them a thin coating of fatty oleic acid to make them biocompatible. The researchers say their discovery has the potential to help treat traumatic brain injury, cardiac arrest and Alzheimer's patients and can guard against radiation-induced side effects suffered by cancer patients.
Their nanoparticles ...