New target to dial down inflammation and pain discovered

Reuters Health - 11/08/2021 - Targeting the production and release of neuronal high-mobility group box 1 protein (HMGB1) may be a novel way to combat diverse disease states characterized by inflammation and pain, such as rheumatoid arthritis or Crohn's disease, research in mice suggests.

"The body's immune system kicks in after an injury and infection and releases molecular proteins like HMGB1 that signal to the body to trigger an inflammatory response. Inflammation is the body's important response mechanism, but if uncontrolled it can lead to many autoimmune disorders or chronic diseases," Dr. Sangeeta S. Chavan of The Feinstein Institutes for Medical Research in Manhasset, New York, told Reuters Health by email.

In a series of preclinical experiments combining optogenetics, neuronal-specific ablation, nerve-injury and inflammatory disease models, with direct assessment of inflammation and neuropathic pain, Dr. Chavan and colleagues demonstrated that release of HMGB1 by sensory neurons is required for a neuroinflammatory response.

These experiments provide "direct evidence that nociceptor-related and pain can be prevented by targeting HMGB1 and has relevance for potential therapy of neuroinflammatory diseases," the researchers write in Proceedings of the National Academy of Sciences (PNAS).

"This discovery is huge," Dr. Chavan told Reuters Health.

"Uncontrolled inflammation is a hallmark for chronic and autoimmune diseases like rheumatoid arthritis, Crohn's, pulmonary hypertension, even diabetes. By honing in on the body's ability to create proteins like HMGB1 to control inflammation, new molecular targets can be explored - whether traditional pharmaceutical drug development or bioelectronic medicine - to control the body's immune response," Dr. Chavan said.

Dr. Chavan cautioned that there is still a lot of preclinical work to be done, but through this discovery "a goal would be to develop clinical trials, including the use of bioelectronic devices, to turn off and on these signals."

This study was supported by grants from the National Institute of Health (NIH). The authors have declared no relevant conflicts of interest.

SOURCE: https://bit.ly/3secoiM Proceedings of the National Academy of Sciences (PNAS), online August 9, 2021.

By Megan Brooks



Posted on 11 August, 20218 April, 2024