Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity Article Swipe
Byron W. Hayes
,
Hae Woong Choi
,
Abhay P. S. Rathore
,
Chunjing Bao
,
Jianling Shi
,
Yul Huh
,
Michael W. Kim
,
Andrea Mencarelli
,
Pradeep Bist
,
Lai Guan Ng
,
C. Shi
,
Joo Hwan Nho
,
Aram Kim
,
Hana Yoon
,
Dong-Hoon Lim
,
Johanna L. Hannan
,
J. Todd Purves
,
Francis M. Hughes
,
Ru‐Rong Ji
,
Soman N. Abraham
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1126/sciimmunol.adi5578
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1126/sciimmunol.adi5578
Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the basis for these bacteria-independent bladder symptoms, we examined the bladders of patients with rUTI. We noticed a notable increase in neuropeptide content in the lamina propria and indications of enhanced nociceptive activity. In mice subjected to rUTI, we observed sensory nerve sprouting that was associated with nerve growth factor (NGF) produced by recruited monocytes and tissue-resident mast cells. Treatment of rUTI mice with an NGF-neutralizing antibody prevented sprouting and alleviated pelvic sensitivity, whereas instillation of native NGF into naïve mice bladders mimicked nerve sprouting and pain behavior. Nerve activation, pain, and urinary frequency were each linked to the presence of proximal mast cells, because mast cell deficiency or treatment with antagonists against receptors of several direct or indirect mast cell products was each effective therapeutically. Thus, our findings suggest that NGF-driven sensory sprouting in the bladder coupled with chronic mast cell activation represents an underlying mechanism driving bacteria-independent pain and voiding defects experienced by patients with rUTI.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1126/sciimmunol.adi5578
- OA Status
- green
- Cited By
- 15
- References
- 112
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4392363495
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4392363495Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1126/sciimmunol.adi5578Digital Object Identifier
- Title
-
Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activityWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-03-01Full publication date if available
- Authors
-
Byron W. Hayes, Hae Woong Choi, Abhay P. S. Rathore, Chunjing Bao, Jianling Shi, Yul Huh, Michael W. Kim, Andrea Mencarelli, Pradeep Bist, Lai Guan Ng, C. Shi, Joo Hwan Nho, Aram Kim, Hana Yoon, Dong-Hoon Lim, Johanna L. Hannan, J. Todd Purves, Francis M. Hughes, Ru‐Rong Ji, Soman N. AbrahamList of authors in order
- Landing page
-
https://doi.org/10.1126/sciimmunol.adi5578Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/11149582Direct OA link when available
- Concepts
-
Nerve growth factor, Mast cell, Interstitial cystitis, Medicine, Lamina propria, Sensory nerve, Urinary system, Inflammation, Pelvic pain, Urinary bladder, Immunology, Sensory system, Submucosa, Nociception, Pathology, Internal medicine, Receptor, Biology, Epithelium, Surgery, NeuroscienceTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
15Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 8, 2024: 7Per-year citation counts (last 5 years)
- References (count)
-
112Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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