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TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

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  • 1Departments of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.

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Chronic pelvic pain following urinary tract infection (UTI) involves TRPV1 in its establishment and CCR2 in its maintenance. These pathways offer potential therapeutic targets for chronic pain after UTI.

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Area of Science:

  • Neuroscience
  • Immunology
  • Urology

Background:

  • The causes of chronic pelvic pain syndromes are not fully understood.
  • Lipopolysaccharide from uropathogenic E. coli and its receptor TLR4 are crucial for developing chronic pain after urinary tract infection (UTI).
  • Downstream molecular mechanisms driving chronic pelvic pain post-UTI require further elucidation.

Purpose of the Study:

  • To investigate the roles of Transient Receptor Potential Vanilloid 1 (TRPV1) and Monocyte Chemoattractant Protein-1 (MCP-1)/C-C chemokine Receptor Type 2 (CCR2) pathways in the development and maintenance of chronic pain following UTI.
  • To explore the involvement of these pathways in associated depressive behaviors.

Main Methods:

  • Utilized a murine model of UTI using E. coli strain SΦ874, known to induce chronic allodynia.
  • Administered TRPV1 antagonist capsazepine at different time points (during infection and two weeks post-infection).
  • Examined TRPV1-deficient mice and employed novelty-suppressed feeding (NSF) tests for depressive behavior.
  • Analyzed MCP-1 and CCR2 expression in sacral dorsal root ganglia using reporter mice.
  • Treated mice with a CCR2 receptor antagonist at two weeks post-infection.

Main Results:

  • Capsazepine treatment during SΦ874 infection prevented the development of chronic allodynia, but treatment two weeks post-infection did not alleviate existing allodynia.
  • TRPV1-deficient mice did not develop chronic allodynia, and similar results were observed for depressive behaviors assessed by NSF.
  • Imaging revealed increased MCP-1 and CCR2 expression in sacral dorsal root ganglia after SΦ874 infection.
  • Administration of a CCR2 receptor antagonist two weeks post-infection successfully reduced chronic allodynia.

Conclusions:

  • TRPV1 plays a critical role in the initial establishment of chronic pain following UTI.
  • The MCP-1/CCR2 pathway is essential for the maintenance of chronic pain after UTI.
  • Targeting TRPV1 during the acute phase and CCR2 during the chronic phase may represent effective therapeutic strategies for post-UTI chronic pelvic pain.