Document Type
Article
Publication Date
5-8-2018
Identifier
DOI: 10.1038/s41598-018-24056-0; PMCID: PMC5940763
Abstract
The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.
Journal Title
Sci Rep
Volume
8
Issue
1
First Page
7188
Last Page
7188
MeSH Keywords
Animals; Capsaicin; Chemokine CCL2; Chronic Pain; Disease Models, Animal; Female; Ganglia, Spinal; Gene Expression Regulation; Hyperalgesia; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Pelvic Pain; Receptors, CCR2; Signal Transduction; TRPV Cation Channels; Toll-Like Receptor 4; Urinary Tract Infections; Uropathogenic Escherichia coli
Keywords
Animals; Capsaicin; Chemokine CCL2; Chronic Pain; Disease Models, Animal; Female; Ganglia, Spinal; Gene Expression Regulation; Hyperalgesia; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Pelvic Pain; Receptors, CCR2; Signal Transduction; TRPV Cation Channels; Toll-Like Receptor 4; Urinary Tract Infections; Uropathogenic Escherichia coli
Recommended Citation
Rosen JM, Yaggie RE, Woida PJ, Miller RJ, Schaeffer AJ, Klumpp DJ. TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain. Sci Rep. 2018;8(1):7188. Published 2018 May 8. doi:10.1038/s41598-018-24056-0
Comments
Grant support
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Publisher's Link: https://www.nature.com/articles/s41598-018-24056-0