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Quantifying pelvic pain in a murine urinary tract infection model, uropathogenic <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>scerichia\u2009coli<\/jats:italic> induces transient pelvic pain, whereas an asymptomatic bacteriuria <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> isolate causes no pain, thus recapitulating the spectrum of clinical responses to intravesical <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic>. These differential pain responses are not correlated with bladder colonization or inflammation, but instead are intrinsic to <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> lipopolysaccharide and dependent on the lipopolysaccharide receptor, <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4. Epidemiological data suggest a link between interstitial cystitis and a history of urinary tract infection, so it was evaluated whether repetitive uropathogenic <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> instillation would result in chronic pain through central sensitization. Although repeated infection with wild type uropathogenic <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> results in only transient episodes of acute pain, a uropathogenic <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> mutant lacking <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>\u2010antigen causes chronic, post\u2010urinary tract infection pelvic pain. Similarly, a <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>\u201012 <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> strain lacking <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>\u2010antigen induces chronic pain that persisted long after bacterial clearance, and expressing <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>\u2010antigen nullified the pain phenotype. Spinal cords isolated from mice with post\u2010urinary tract infection chronic pain showed deficits in short\u2010term depression consistent with central sensitization. Deleting <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>\u2010antigen gene complex from a uropathogenic <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> strain and subsequent heterologous expression of <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>\u2010antigen gene clusters shows that a single bacterial isolate can exhibit pain phenotypes ranging from a null phenotype, an acute pain phenotype, to a chronic pain phenotype. Post\u2010urinary tract infection chronic pain is also associated with voiding dysfunction and anxious\/depressive behavior. These effects are also mediated by <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1 at the level of pain establishment and <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2 at the level of pain maintenance. Together, these findings show that transient infection with <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> might result in chronic visceral pain with the hallmarks of neuropathic pain. This pattern of behaviors mimics the spectrum of interstitial cystitis symptoms, thus supporting the possibility of an infectious etiology of interstitial cystitis.<\/jats:p>","DOI":"10.1111\/iju.12309","type":"journal-article","created":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T02:46:29Z","timestamp":1399517189000},"page":"26-32","source":"Crossref","is-referenced-by-count":47,"title":["Mechanisms of pain from urinary tract infection"],"prefix":"10.1111","volume":"21","author":[{"given":"John M","family":"Rosen","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology Ann and Robert H Lurie Children's Hospital  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Klumpp","sequence":"additional","affiliation":[{"name":"Department of Urology Feinberg School of Medicine Northwestern University  Chicago Illinois USA"},{"name":"Department of Microbiology\u2010Immunology Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1047-2797(00)00072-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2008.09.014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)00053-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00796-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.16.8829"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00376-06"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5393.1494"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134258"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741\u20107015\u20108\u201030"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-011-2089-1"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1975.tb03859.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.59.9.2915-2921.1991"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028289"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.429-432.1999"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.1.781-785.2006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28711-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-010-0532-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01271-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/171.2.462"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.116"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/323891"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.12.041"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00275-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20670"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/651275"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002096"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041273"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000415"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135414"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00101.x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002400000114"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3179-3186.2004"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030060"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5472.1765"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00069-08"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01013-07"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.18.5699-5704.1991"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1128\/jb.126.2.999-1001.1976","article-title":"Altered deoxyribonucleotide pools in P2 eductants of Escherichia coli K\u201012 due to deletion of the dcd gene","volume":"126","author":"Neuhard J","year":"1976","journal-title":"J. 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