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O-antigen modulates infection-induced pain states
Charles N Rudick1, Mingchen Jiang, Ryan E Yaggie
1Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Plos One
|August 18, 2012
Summary
The O-antigen of E. coli modulates pain during urinary tract infections independently of inflammation. This bacterial component acts as a rheostat, influencing the severity and duration of infection-associated pain.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- The molecular mechanisms driving pain associated with infections remain largely unknown.
- Uropathogenic E. coli (UPEC) causes acute pelvic pain in murine urinary tract infections (UTIs), linked to lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4), but not inflammation.
- The role of LPS's O-antigen polysaccharide in host responses, particularly pain, is unexplored.
Purpose of the Study:
- To investigate the function of the O-antigen polysaccharide in modulating pain during murine UTIs.
- To determine if O-antigen influences pain independently of inflammatory responses.
- To explore the central nervous system mechanisms underlying O-antigen-mediated pain.
Main Methods:
- Utilized murine UTI models to quantify pelvic pain behavior via cutaneous allodynia.
- Assessed central nervous system changes using sacral spinal cord excitability measurements.
- Employed UPEC mutants deficient in O-antigen biosynthesis and strains with manipulated O-antigen gene clusters.
- Examined pain phenotypes in TLR4-deficient mice and compared inflammatory markers across different strains.
Main Results:
- A UPEC mutant lacking O-antigen induced chronic allodynia, persisting post-infection, unlike wild-type UPEC causing acute pain.
- Modifying O-antigen expression altered the pain phenotype predictably, with strains lacking O-antigen gene clusters showing chronic pain.
- Chronic allodynia was absent in TLR4-deficient mice, yet inflammatory responses were similar across strains with varying pain phenotypes.
- Spinal cords of mice with chronic allodynia displayed increased spontaneous firing and reduced short-term depression, indicative of centralized pain.
Conclusions:
- E. coli O-antigen acts as a rheostat, modulating LPS-induced pain independently of inflammation.
- These findings suggest a novel mechanism for infection-associated chronic pain and potential pathogen adaptations to alter host behavior.
- Understanding O-antigen's role has implications for developing targeted therapies for infectious pain conditions.
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