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Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.

Publication ,  Journal Article
Hayes, BW; Choi, HW; Rathore, APS; Bao, C; Shi, J; Huh, Y; Kim, MW; Mencarelli, A; Bist, P; Ng, LG; Shi, C; Nho, JH; Kim, A; Yoon, H ...
Published in: Sci Immunol
March 2024

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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Published In

Sci Immunol

DOI

EISSN

2470-9468

Publication Date

March 2024

Volume

9

Issue

93

Start / End Page

eadi5578

Location

United States

Related Subject Headings

  • Urinary Bladder
  • Reinfection
  • Pain
  • Nerve Growth Factor
  • Mice
  • Mast Cells
  • Humans
  • Female
  • Animals
  • 3204 Immunology
 

Citation

APA
Chicago
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Hayes, B. W., Choi, H. W., Rathore, A. P. S., Bao, C., Shi, J., Huh, Y., … Abraham, S. N. (2024). Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity. Sci Immunol, 9(93), eadi5578. https://doi.org/10.1126/sciimmunol.adi5578
Hayes, Byron W., Hae Woong Choi, Abhay P. S. Rathore, Chunjing Bao, Jianling Shi, Yul Huh, Michael W. Kim, et al. “Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.Sci Immunol 9, no. 93 (March 2024): eadi5578. https://doi.org/10.1126/sciimmunol.adi5578.
Hayes BW, Choi HW, Rathore APS, Bao C, Shi J, Huh Y, et al. Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity. Sci Immunol. 2024 Mar;9(93):eadi5578.
Hayes, Byron W., et al. “Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.Sci Immunol, vol. 9, no. 93, Mar. 2024, p. eadi5578. Pubmed, doi:10.1126/sciimmunol.adi5578.
Hayes BW, Choi HW, Rathore APS, Bao C, Shi J, Huh Y, Kim MW, Mencarelli A, Bist P, Ng LG, Shi C, Nho JH, Kim A, Yoon H, Lim D, Hannan JL, Purves JT, Hughes FM, Ji R-R, Abraham SN. Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity. Sci Immunol. 2024 Mar;9(93):eadi5578.

Published In

Sci Immunol

DOI

EISSN

2470-9468

Publication Date

March 2024

Volume

9

Issue

93

Start / End Page

eadi5578

Location

United States

Related Subject Headings

  • Urinary Bladder
  • Reinfection
  • Pain
  • Nerve Growth Factor
  • Mice
  • Mast Cells
  • Humans
  • Female
  • Animals
  • 3204 Immunology