Scratching deep beneath the surface, a team of researchers from the University of California, San Diego School of Medicine and three South Korean institutions have identified two distinct neuronal signaling pathways activated by a topical cream used to treat a variety of skin diseases. One pathway produces the therapeutic benefit; the other induces severe itching as a side effect.
The findings, published in this week's early online edition of the Proceedings of the National Academy of Sciences, point to the possibility of designing future drugs that effectively treat targeted conditions while blocking the cellular signals that can lead to problematic itching and scratching.
"This new pathway provides another avenue to block the scratching response that appears as a chronic side effect during treatments of cancer, renal failure or the use of some antibiotics," said Melvin I. Simon, PhD, an adjunct professor in the UCSD Department of Pharmacology and a corresponding co-author of the study, headed by Sang-Kyou Han, an adjunct assistant professor at UC San Diego.
Itching – and the scratching response – are part of a complex and imperfectly understood somatosensory process that includes complex, confounding psychological factors. The mechanisms involved are so sophisticated, said Simon, that just reading or thinking about itching can provoke the sensation.
Improving understanding of itch biology isn't just a matter of scratching an intellectual curiosity. It could lead to practical medical benefits, according to Simon. "Itching and scratching are side effects of a variety of therapeutic drugs and of specific illnesses. In many cases, these effects are severe and make it impossible to use otherwise effective therapies. Thus, the itch remains an unmet medical need."
In the PNAS study, the scientists focused on Imiquimod (marketed as Aldara), a prescription-based topical cream used to treat a number of skin diseases, including some forms of skin cancer, by activating the body's innate immune response. One major side effect: Imiquimod produces intense itching and scratching.
The researchers discovered that the skin sensory circuit activated by Imiquimod to causes itching is different from the signaling pathway involved in the drug's therapeutic benefit. Indeed, the Imiquimod itch mechanism is distinct from other, well-defined itch mechanisms.
"By breaking down the response and sorting out its various elements, it may be possible to both understand the molecular mechanisms involved and to control them," said Simon, who noted more research is planned.
Co-authors of the paper are Se-Jeong Kim of UCSD's Department of Pharmacology and the Department of Neuroscience, Dental Research Institute and Brain Korea21, School of Dentistry, Seoul National University; Goon Ho Park, Hyejung Min and Estelle Wall, UCSD Department of Pharmacology; Donghoon Him and Sung Joong Lee, Department of Neuroscience, Dental Research Institute and Brain Korea21, School of Dentistry, Seoul National University; Jaekwang Lee and C. Justin Lee of the Center for Functional Connectomics, Korea Institute of Science and Technology.
Scott LaFee | EurekAlert!
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research