Nerve Cells Responsible for Pain Detection Could Offer New Strategies to Treat Lung Scarring

Researchers at the University of Calgary have uncovered a surprising role for pain-sensing nerves in protecting against pulmonary fibrosis, a severe lung disease characterized by scarring. Pulmonary fibrosis is a rare but often fatal condition, with most patients dying within five years of diagnosis. Traditionally, research focused on how lung tissue damages and attempts at repair, but new findings point to the nervous system's involvement.

The team led by Dr. Bryan Yipp discovered that specific neurons, known for their role in pain detection, also help regulate inflammatory responses in the lungs. In experiments using mice, when these pain-detecting nerve cells were eliminated—either through drugs or genetic modifications—the immune system became dysregulated, resulting in increased lung inflammation and tissue damage.

Further investigation revealed that without these nerve cells, alveolar macrophages (immune cells in the lungs) started producing a nerve communication molecule called VIP, which isn't normally produced in large amounts by these cells. Elevated VIP levels were associated with worsening lung damage, but blocking VIP or deleting its production improved lung health by reducing harmful inflammation.

The study, titled "Nociceptor neurons suppress alveolar macrophage-induced Siglec-F+ neutrophil-mediated inflammation to protect against pulmonary fibrosis," was published in the journal Immunity. Dr. Yipp explained that current treatments often focus on the lung tissue itself, but understanding the nervous system's role opens up promising new avenues for therapy. Electrical stimulation therapies used for conditions like seizures and mood disorders could potentially be adapted to boost nerve function in the lungs, helping to prevent or slow scarring.

Annually, around 2,500 Canadians succumb to lung scarring, and thousands live with the condition. This research aims to develop innovative treatments targeting nerve interactions to combat pulmonary fibrosis more effectively.