Bacterial Cystitis is Accompanied by Increased Peripheral Thermal Sensitivity in Mice

Bjorling, Dale E.; Wang, Zunyi; Boldon, Kyle; Bushman, Wade

doi:10.1016/j.juro.2007.09.024

Cited by 18 publications

(13 citation statements)

References 20 publications

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“…Although TLR4 involvement is well documented for bacterial defense it has only recently be implicated in nociception. Similar to the results presented here, one previous study demonstrated enhanced thermal sensitivity in mice infected with bacteria [36]. Furthermore, our study is first, to our knowledge, to demonstrate that LPS is the initiator of UTI-induced pelvic pain.…”

Section: Discussionsupporting

confidence: 91%

Host‐Pathogen Interactions Mediating Pain of Urinary Tract Infection

Rudick¹,

Billips²,

Pavlov³

et al. 2010

J INFECT DIS

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Background Pelvic pain is a major component of the morbidity associated with urinary tract infection (UTI), yet the molecular mechanisms underlying UTI-induced pain remain unknown. UTI pain mechanisms likely contrast with the clinical condition of asymptomatic bacteriuria (ASB), where individuals have significant bacterial loads yet lack symptoms. Methods A murine UTI model was used to compare pelvic pain behavior elicited by infection with uropathogenic Escherichia coli strain NU14 and ASB strain 83972. Results NU14-infected mice developed pelvic pain, whereas mice infected with 83972 did not exhibit pain, similar to patients infected with 83972. NU14-induced pain was not dependent on mast cells, not correlated with bacterial colonization, nor correlated urinary neutrophils. UTI pain was not influenced by expression of type 1 pili, the bacterial adhesive appendage that induces urothelial apoptosis. However, purified NU14 lipopolysaccharide (LPS) induced TLR4-dependent pain, but 83972 LPS induced no pain. Indeed, 83972 LPS attenuated pain of NU14 infection, suggesting therapeutic potential. Conclusions These data suggest a novel mechanism of infection-associated pain that is dependent on TLR4 yet independent of inflammation. Clinically, these findings also provide the rational for probiotic therapies that would minimize the symptoms of infection without reliance on empiric therapies that contribute to antimicrobial resistance.

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Section: Discussionsupporting

confidence: 91%

Host‐Pathogen Interactions Mediating Pain of Urinary Tract Infection

Rudick¹,

Billips²,

Pavlov³

et al. 2010

J INFECT DIS

View full text Add to dashboard Cite

show abstract

“…In addition to the involvement of TRPV1 afferents in pelvic sensitivity, other receptors and molecules can also contribute to abdominal hyperalgesia depending on the model and nature of chosen inflammatory agents [81]. Thus, increased peripheral sensitivity in mice with bacterial cystitis was related to activation of toll-like receptor 4 [82]. In the acrolein model of bladder inflammation in rats, increased mechanical sensitivity was conveyed, in part, via NGF and trk receptors [83].…”

Section: Discussionmentioning

confidence: 99%

VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

Malykhina

Erickson

et al. 2012

BMC Physiol

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BackgroundThis work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments.ResultsIn addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation.ConclusionsFor the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and enhanced VEGF content may be associated with visceral hyperalgesia, abdominal discomfort, and/or pelvic pain.

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“…to injure the bladder. Evoked pain behaviors, visceromotor response to distension, or secondary hyperalgesia on the abdomen or paw is assessed [19;116;181]. …”

Section: Animal Models Of Diseasementioning

confidence: 99%

An Overview of Animal Models of Pain: Disease Models and Outcome Measures

Gregory

Harris

Robinson

et al. 2013

The Journal of Pain

334

255

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Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience including reflexive hyperalgesia measures, sensory and affective dimensions of pain and impact of pain on function and quality of life. In this review we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes, as well as the main behavioral tests for assessing pain in each model.

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Bacterial Cystitis is Accompanied by Increased Peripheral Thermal Sensitivity in Mice

Cited by 18 publications

References 20 publications

Host‐Pathogen Interactions Mediating Pain of Urinary Tract Infection

Host‐Pathogen Interactions Mediating Pain of Urinary Tract Infection

VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

An Overview of Animal Models of Pain: Disease Models and Outcome Measures

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