Author Archives: Ana Pena PhD

Neuronal Circuit Likely Behind Chronic Itch in MS and Other Diseases Identified

The nerve cell circuit, stretching from the skin to the spinal cord, that is likely responsible for the persistent itching sensation  that can afflict people with multiple sclerosis (MS) and other conditions was identified in a study. The discovery was made in mice and as such is still preliminary, but researchers say this work may lead to specific treatments for chronic itch. The study "Identification of a Spinal Circuit for Mechanical and Persistent Spontaneous Itch" was published in the journal Neuron. People with MS can experience a range of altered and unpleasant sensations — frequently described as a tingling, itching, burning or aching feeling, or a “girdling” sensation across the body (popularly called the “MS hug”). These sensations are collectively known as dysesthesia. They are caused by damage to nerves that perturbs the normal transmission of messages to and from the brain. Chronic itch, that which lasts for six or more weeks, also troubles people with conditions such as eczema, nerve damage caused by diabetes (diabetic neuropathy), and cancer. Patients can show extra sensitivity to what's called mechanical itch — which normally comes from a light brushing or poking against the skin — as well as to persistent spontaneous itch. (Chemical itch, in contrast, is a response to things like an insect bite and linked to activation of the histamine system.) The underlying neural circuits are not well-defined, and no effective treatments exist. Researchers at the University of Michigan investigated in detail the mechanisms behind chronic mechanical itch, looking for possible treatment approaches. To narrow down which nerve cells (neurons) account for mechanical itch, they individually removed nine distinct groups of spinal neurons from mice. One, called excitatory interneurons, had high levels of a protein called Urocortin 3 (Ucn3); these neurons were central for the transmission of both acute and persistent mechanical itch. "Behavioral analysis after the ablations of these neuronal subsets revealed that Ucn3 neurons are the mechanical itch transmission neurons," Mahar Fatima, PhD, a study co-author, said in a university news release. Removing the other spinal neuronal groups did not "affect the transmission of mechanical itch," Fatima added. According to the team, a mechanical itch starts upon activation of specialized sensory cells found in skin, called Toll-like receptor 5-positive low-threshold mechanoreceptors. These cells react to a light touch, passing the message along to Ucn3 interneurons in the spinal cord. Researchers also found a third important player, called inhibitory interneurons expressing neuropeptide Y (NPY). These nerve cells control Ucn3 neuronal activity; that is, they control how much skin "tickling" is needed to cause itching. In other words, the researchers said, these inhibitory interneurons are "the gatekeepers" of sensitivity to itch. If they are defective, a person could experience chronic itch. To confirm that this neuronal circuit was indeed responsible for mechanical itch, the team manipulated mice to either lack Ucn3 neurons or to shut down their activity. Mice so altered stopped responding to a light tickle behind the ear, even though they still reacted to a chemical that triggers itching. This indicated that the chemical and mechanical itch pathways are separate, and that Ucn3 neurons are solely contributing in the latter pathway, the researchers said. In each of various experiments, the mice’s ability to sense touch, pain, or thermal sensation were not affected, demonstrating the specific role of these neurons in itching. Further mice experiments suggested that under chronic itch conditions, NYP interneurons do not work properly, preventing Ucn3 neurons from stopping as they should, and making them more prone to being overactive. This, the research team said, may explain why patients with chronic itch have heightened sensitivity and a tendency for persistent spontaneous itch. Consistent with this hypothesis, removing Ucn3 neurons from mice prevented mechanical itch sensitization and persistency in the animals. "Itching is one of the major symptoms in most skin disorders and other neurologic disorders," Bo Duan, the study's senior leader, said. "This is one mechanism we needed to understand to develop a new treatment for patients with chronic itch."

UK Researchers Pursuing Breath Test to Diagnose MS

Scientists at the University of Huddersfield, U.K., are trying to develop a breath test to detect volatile molecules exhaled only by people with multiple sclerosis (MS). Doing so might offer a non-invasive and simple way to diagnose the disease. The research team now plans to undertake…

NervGen to Advance NVG-291 as Potential Remyelination Therapy for MS

NervGen wants to advance the development of NVG-291, its lead investigational therapy for spinal cord damage, as a potential remyelination treatment for multiple sclerosis (MS), the company announced. Following preclinical data showing that NVG-291 promotes myelin repair and regeneration of damaged nerves in animal models of…

Obesity, Altered Fat Levels May Worsen Severity of RRMS, Study Found

Obesity, altered lipid (fat) levels, and elevated leptin — an hormone produced by fat cells — may contribute to neuroinflammation, and worse disease severity in people with relapsing-remitting multiple sclerosis (RRMS), research has found. A study with the findings, titled “Obesity worsens central inflammation and disability in multiple…

Study Will Explore Benefits of Tai Chi, Meditation on MS Patients’ Physical Balance

A pilot study has been launched to assess the immediate and enduring benefits of tai chi and mindfulness meditation on the physical balance and mental wellness of people with multiple sclerosis (MS). This community-based study — currently enrolling participants — is being conducted by the Motor Control Lab directed by Richard van Emmerik, PhD, professor of kinesiology at the University of Massachusetts Amherst. The project was awarded a $54,972 one-year grant from the National Multiple Sclerosis Society. While many MS symptoms vary from patient to patient, depending on the extent and location of the damage in the brain and spinal cord, difficulty in maintaining physical balance is a generalized complaint. Several MS symptoms can have an effect on balance, including difficulties with coordination, tremor and muscle weakness, stiffness, or dizziness and vertigo. "Mind-body interventions are beneficial as they train dynamic balance, such as transitioning between postures, turning, reaching, etc., in a manner similar to movements in daily life," Julianna Averill, a doctoral student at van Emmerik’s lab, said in a press release. Postural control and balance confidence is crucial to prevent patients' falls and reduce their fear of falling. Finding strategies that help patients cope and overcome this limitation is crucial, Averill noted. Contrary to other studies, which focus on mental health benefits, this project will look mostly at the effects of mindfulness practice on physical balance. Tai chi also will be evaluated for its potential to improve patients’ balance, both while they are standing and as they move. Participants will be randomly assigned to either eight weeks of free tai chi at YMAA Western Mass Tai Chi or mindfulness meditation classes at Downtown Mindfulness, in Hampshire County, Massachusetts. Tai chi is a Chinese martial art that involves body stretching and slow, focused, flowing postures that keep the body in motion. Mindfulness meditation is based on mindfulness practices, including training on body scan meditation, and loving kindness meditation. Participants will attend classes for 2.5 hours per week, where they will receive training to complete an additional 2.5 hours at home each week. At home, participants are asked to listen to meditation podcasts, or watch tai chi videos via a website that also tracks their activity. “The participants will be trained, and they will be able to practice on their own,” Averill said. Patients' postural sway will be recorded by wearable sensors while performing distinct movements at the study start, at the end of all classes, and two weeks later. On the same visits, participants will be surveyed to assess the frequency of falls, balance confidence, level of fatigue, and ability to cope and adapt. “We’re taking a more holistic look, considering the whole person and overall quality of life,” Averill said. The team plans to enroll 30 participants with mild-to-moderate MS symptoms, aged 21 to 70, and who are able to stand and move without assistance for 15 minutes. For more information about the study and how to participate, contact Averill at [email protected]

Acrolein Eyed as Potential Biomarker of MS, Preliminary Study Finds

A product called acrolein, which is naturally excreted by the body and possible to measure in urine and blood, may be a potential biomarker to help diagnose and evaluate disease activity in people with multiple sclerosis (MS), according to preliminary research in animal models and humans. Researchers are investigating whether acrolein…

Patients with Stable Disease Who Switch to Another Interferon Therapy at Greater Risk of Flares, Study Reports

Multiple sclerosis (MS) patients who have been relapse-free while using an interferon-beta (IFN-β) therapy but switch to another IFN-β are significantly more like to start experiencing flares than patients who remain on their initial interferon treatment, a real-world study reports. Its results support letting patients remain on a current IFN-β medication…

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