Posts tagged itch
Articles and news from the latest research reports.
One Molecule To Block Both Pain And Itch
Duke University researchers have found an antibody that simultaneously blocks the sensations of pain and itching in studies with mice.
The new antibody works by targeting the voltage-sensitive sodium channels in the cell membrane of neurons. The results appear online on May 22 in Cell.
Voltage-sensitive sodium channels control the flow of sodium ions through the neuron’s membrane. These channels open and close by responding to the electric current or action potential of the cells. One particular type of sodium channel, called the Nav1.7 subtype, is responsible for sensing pain.
Mutations in the human gene encoding the Nav1.7 sodium channel can lead to either the inability to sense pain or pain hypersensitivity. Interestingly, these mutations do not affect other sensations such as touch or temperature. Hence, the Nav1.7 sodium channel might be a very specific target for treating pain disorders without perturbing the patients’ ability to feel other sensations.
"Originally, I was interested in isolating these sodium channels from cells to study their structure," said Seok-Yong Lee, assistant professor of biochemistry in the Duke University Medical School and principal investigator of the study. He designed antibodies that would capture the sodium channels so that he could study them. "But then I thought, what if I could make an antibody that interferes with the channel function?"
The team first tested the antibody in cultured cells engineered to express the Nav1.7 sodium channel. They found that the antibody can bind to the channel and stabilize its closed state.
"The channel is off when it is closed," Lee explained. "Since the antibody stabilizes the closed state, the channel becomes less sensitive to pain." If this held true in live animals, then the animals would also be less sensitive to pain.
To test this idea, Lee sought the help of Ru-Rong Ji, professor of anesthesiology and neurobiology, who is an expert in the study of pain and itch sensation. Using laboratory mouse models of inflammatory and neuropathic pain, they showed that the antibody can target the Nav1.7 channel and reduce the pain sensation in these mice. More importantly, mice receiving the treatment did not show signs of physical dependence or enhanced tolerance toward the antibody.
"Pain and itch are distinct sensations, and pain is often known to suppress itch", said Ji.
The team found that the antibody can also relieve acute and chronic itch in mouse models, making them the first to discover the role of Nav1.7 in transmitting the itch sensation.
"Now we have a compound that can potentially treat both pain and itch at the same time," said Lee. Both of these symptoms are common in allergic contact dermatitis, which affects more than 10 million patients a year in the United States alone.
The team is pursuing a patent for the antibody.
"We hope our discovery will garner interest from pharmaceutical companies that can help us expand our studies into clinical trials," Lee said. Their goal is to develop a safer treatment for pain and itch as an alternative to opioids, which often cause addiction and other detrimental side effects.
(Source: today.duke.edu)
Dynorphin Acts as a Neuromodulator to Inhibit Itch in the Dorsal Horn of the Spinal Cord
Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5−/− mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.
These scientists are ‘itching’ to help you stop scratching
Itch and scratch, itch and scratch. It’s not the most serious physical problem in our lives, but it is common and it is very annoying. Now, researchers at the Hebrew University of Jerusalem and in Boston have come up with new findings that can stop the itching through silencing the neurons that transmit itch-generating stimuli.
The research was a collaborative effort by a group led by Dr. Alex Binshtok at the Hebrew University’s Department of Medical Neurobiology at the Institute of Medical Research Israel-Canada, and the Edmond & Lily Safra Center for Brain Sciences; along with Dr. Clifford Woolf’s group in the Boston Children’s Hospital and Harvard Medical School.
The study demonstrated the presence of functionally distinct sets of neurons that detect and transmit itch-generating stimuli. The researchers were further able to demonstrate that they could selectively target and silence those itch-generating neurons while active. These results provide a basis for the development of novel therapeutic approaches for selective treatment of previously unmet itching not induced by histamine (non-histaminergic itch), such as dry skin itch and allergic dermatitis.
(Histaminergic itch is brought on when histamine triggers an inflammatory immune response to foreign agents, such as occurs, for example, in hay fever.)
The findings of the Israeli-US researchers were published in the journal Nature Neuroscience. In addition to the senior researchers, student major contributors to the project were Sagi Gudes and Felix Blasl from the Hebrew University; and David Roberson and Jared Sprague from Harvard Medical School.
Itch is a complex, unpleasant, cutaneous sensation that in some respects resembles pain, yet is different in terms of its intrinsic sensory quality and the urge to scratch. Although some types of itch like urticaria (hives) could be effectively treated with anti-histaminergic agents, itch accompanying most chronic itch-inducing diseases, including atopic dermatitis (eczema), allergic itch and dry skin itch, is not predominantly induced by histamine. An understanding of the molecular and cellular mechanisms underlying the sensation of itch, therefore, is essential for the development of effective and selective treatment of itch, which in some cases could become a devastating condition, say the researchers.
The researchers’ findings suggest that primary itch-generating neurons that carry messages toward the central nervous system code functionally distinct histaminergic and non-histaminergic itch pathways that could be selectively blocked. This is the first time that this has been demonstrated, and means that it is possible to block itch signals in the neurons that mediate non-histamine itch.
These findings have a great clinical importance since they could be translated into novel, selective and effective therapies for previously largely untreated dry skin itch and allergic dermatitis itch.