Home Medizin Nervenüberwucherung als Schmerzursache bei wiederkehrenden Harnwegsinfekten identifiziert

Nervenüberwucherung als Schmerzursache bei wiederkehrenden Harnwegsinfekten identifiziert

von NFI Redaktion

People with recurrent urinary tract infections (UTI) often experience persistent pain even after antibiotics successfully eliminate the bacteria.

Researchers at Duke Health have now identified the likely cause – an excessive growth of nerve cells in the bladder.

The findings, published on March 1st in the journal Science Immunology, offer a potential new approach to treating the symptoms of recurrent UTIs, addressing the issue more effectively and reducing the unnecessary use of antibiotics.

„Urinary tract infections account for almost 25% of infections in women,“ said lead author Soman Abraham, Ph.D., Professor in the Departments of Pathology, Molecular Genetics and Microbiology, Integrative Immunobiology, and Cell Biology at Duke University School of Medicine.

„Many of these are recurrent urinary tract infections, with patients often complaining of chronic pelvic pain and frequent urination, even after a round of antibiotics,“ Abraham said. „Our study describes for the first time an underlying cause and identifies a potential new treatment strategy.“

Abraham and colleagues collected bladder biopsies from recurrent UTI patients who experienced pain even though no culturable bacteria were found in their urine. Comparing biopsies from individuals without UTIs found evidence that sensory nerves were highly activated in UTI patients, explaining the persistent pain and frequency of urination.

Further studies in mice revealed the underlying events, namely unique conditions in the bladder that cause activated nerves in the mucosa to bloom and grow with each infection.

„Normally, with each episode of UTI, bacteria-laden epithelial cells are shed, leading to significant destruction of surrounding nerve tissue,“ said Byron Hayes, lead author of the study and former postdoctoral fellow in Duke’s Department of Pathology. „These events trigger a rapid repair program in the damaged bladder, resulting in massive regrowth of destroyed nerve cells.“

This immune response, including repair activities, is controlled by mast cells – immune cells that fight infections and allergens. Mast cells release chemicals known as nerve growth factor that promote excessive growth and increased sensitivity of nerves. The result is pain and urgency.

The researchers were able to combat these symptoms by treating study mice with molecules that suppress the production of nerve growth factor produced by mast cells.

„This work helps to elucidate a mysterious clinical condition that drives up medical costs and impairs the quality of life for millions of people, especially women,“ said Abraham. „Understanding the interaction between mast cells and nerves is a crucial step towards effective treatments for those suffering from recurrent UTIs.“


Soman Abraham, Ph.D., lead author

Study co-authors include Hae Woong Choi, Abhay PS Rathore, Chunjing Bao, Jianling Shi, Yul Huh, Michael W Kim, Andrea Mencarelli, Pradeep Bist, Lai Guan Ng, Changming Shi, Joo Hwan Nho, Aram Kim, Hana Yoon, Donghoon Lim, Johanna L. Hannan, J. Todd Purves, Francis M. Hughes Jr., and Ru-Rong Ji.

The study received financial support from the National Institutes of Health (K12-DK100024, R01-DK121969, R01-DK121032, R01-GM144606), the National Research Foundation of Korea (2020R1C1C1003257), and a scholarship from Korea University.

Source:

Duke University Medical Center

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