JUN 26, 2015 03:57 PM PDT

Attacking Asthma

While asthma medications that suppress inflammatory signaling by immune cells or dilate airways are effective, they can stop working after awhile. Researchers at Boston Children's Hospital, Brigham and Women's Hospital and Harvard Medical School think they have an alternative approach to controlling asthma: targeting nociceptors -- sensory nerve endings in the lungs that help drive allergic inflammation, according to a study published in the journal Neuron and reported in Medical News Today(http://www.medicalnewstoday.com/releases/295944.php).
Researchers target sensory receptors to attack asthma.
The National Heart, Ling and Blood Institute, part of the National Institutes of Health, explains that asthma affects more than 25 million Americans, about 7 million of whom are children. It affects people of all ages, often starting during childhood. Asthma, a chronic lung disease, inflames and narrows the airways. It causes recurring periods of wheezing, chest tightness, shortness of breath and nighttime or early morning coughing (http://www.nhlbi.nih.gov/health/health-topics/topics/asthma).

Nociceptors are activated by allergic inflammation and worsen the allergic immune response, the researchers say. Silencing them selectively in mouse models of acute and chronic asthma reduces inflammation and bronchial twitchiness. The nociceptors in the lungs connect to the brainstem, triggering the cough reflex when they sense dust particles, chemical irritants, allergens and other substances. While nociceptor nerve endings appear to be more plentiful and more readily activated in asthmatics, their role in causing allergic inflammation was not explored in the past.

According to Clifford Woolf, M.D., Ph.D., director of the F.M. Kirby Neurobiology Center at Boston Children's Hospital and a co-senior investigator on the study, "An attractive aspect of targeting nociceptors is that this approach would be most effective when inflammation is already present and should accelerate its resolution."

Co-senior investigator Bruce Levy, M.D., chief of the Pulmonary and Critical Care Medicine Division at Brigham and Women's Hospital, adds, "Current asthma treatments can help to control symptoms and dampen airway inflammation; however, therapies are not available to promote the resolution of asthma. A treatment to interrupt the vicious cycle of neuro-immune signaling holds promise as a disease-modifying therapy and is mechanistically distinct from any of the currently available asthma therapies."

The researchers tested a strategy for selectively blocking nociceptor activity in mice using a drug called QX-314, which specifically blocks pain neurons that are activated by inflammation. Knowing that neurons and the immune system communicate, they wanted to see how that works in asthmatics. The researchers induced asthma in mice by exposing them to dust mites or another allergen, ovalbumin, then administered QX-314 via nebulizer to silence the nociceptors. They found that, when stimulated, nociceptors release chemicals (neuropeptides) that "cause immune cells to infiltrate the lungs and become more active." Then, IL-5, an inflammatory molecule produced by the immune cells, activates the nociceptors to produce a neuropeptide called vasoactive intestinal peptide (VIP), which stimulates the inflammatory response and creates a neuro-immune feedback loop that inflames the lungs and escalates asthma symptoms. Silencing the nociceptors, either genetically or with QX-314, results in much less airway inflammation and less bronchial twitchiness. Thus, the researchers conclude that "nociceptors both react to and drive inflammatory immune responses in the lung, and that silencing these cells interrupts this feedback loop, helping relieve allergic airway inflammation and bronchospasm."
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
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