Urogenit Tract Infect.  2016 Aug;11(2):49-55. 10.14777/uti.2016.11.2.49.

New Era of Post Urinary Tract Infection Pain Syndrome

• Lee KW
• Kim YH

• KMID: 2350756
• DOI: http://doi.org/10.14777/uti.2016.11.2.49

Abstract

Urinary tract infection (UTI) in most cases is accompanied by pain. However, in some cases, including asymptomatic bacteriuria (ASB), pain is absent and thus, cannot be characterized. A study with an animal UTI model to quantify pelvic pain showed that Escherichia coli (NU14 strains) isolated from urine of patients with acute UTI caused pain, while E. coli (83972 strains) isolated from urine of patients with ASB caused no pain. The difference in pain response was not related to bladder colonization or inflammation, but to lipopolysaccharde (LPS) and Toll-like receptor 4, which is an LPS receptor. As the association between interstitial cystitis (IC) and UTI was epidemiologically suggested, an experiment was performed to investigate whether repeated infection with uropathogenic E. coli (UPEC) causes chronic pain through central sensitization. The results showed that repeated infection with the wild type UPEC caused temporary pain, while repeated infection with UPEC (SΦ 874 strains) in the absence of O-antigen caused chronic pain. Chronic pain following UTI is related to voiding dysfunction and anxious/depressive behavior. These relationships are mediated by transient receptor potential vanilloid type 1 at the stage of pain development and by C-C chemokine receptor type 2 at the stage of pain maintenance. Based on these findings, temporary E. coli infection causes chronic pain, which is one of the characteristics of neuropathic pain. This pattern is similar with the symptoms of IC, supporting the possibility of infection as an etiology of IC.

Keyword

Urinary tract infections; Pain; Interstitial cystitis

MeSH Terms

Animals
Antigens, CD14
Bacteriuria
Central Nervous System Sensitization
Chronic Pain
Colon
Cystitis, Interstitial
Escherichia coli
Humans
Inflammation
Neuralgia
Pelvic Pain
Toll-Like Receptor 4
Urinary Bladder
Urinary Tract Infections*
Urinary Tract*
Antigens, CD14
Toll-Like Receptor 4

Figure

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  Fig. 1. Diagram of hypothesized mechanism underlying the progression from recurrent cystitis to interstitial cystitis. Adapted from Kim and Kim, Inflammation and interstitial cystitis. Book of 2nd International Consultation on Interstitial Cystitis, Japan; 2007. p. 33-7, with permission [4]. UTI: urinary tract infection, CIBD: chronic inflammatory bladder disease, IC: interstitial cystitis.

• 

  Fig. 2. Lipopolysaccharde (LPS) mediates urinary tract infection pain, independent of inflammation. Adapted from the article of Rosen and Klumpp, Int J Urol 2014;21 Suppl 1:26-32, with permission [42].

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  Fig. 3. Post-urinary tract infection chronic pain is mediated by multiple receptors. Adapted from the article of Rosen and Klumpp, Int J Urol 2014;21 Suppl 1: 26-32, with permission [42]. LPS: lipopolysaccharide, TLR4: Toll-like receptor 4, MCP-1: monocyte chemotactic protein 1, CCR2: C-C chemokine receptor type 2, TRPV1: transient receptor potential vanilloid type 1, GABA: gamma-aminobutyric acid.

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