{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T01:27:38Z","timestamp":1786584458468,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,10]]},"group-title":"Neuroscience","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["NIDDK 1R01DK134817"],"award-info":[{"award-number":["NIDDK 1R01DK134817"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Urinary tract infections (UTIs) are a major risk factor for interstitial cystitis\/bladder pain syndrome (IC\/BPS), yet the mechanisms driving chronic pelvic pain and associated symptoms remain poorly understood. Here, we investigated the role of microglia and Toll-like receptor 4 (TLR4) in a mouse model of post-UTI chronic pelvic pain (PUPP). Infection with\n                  <jats:italic>E. coli<\/jats:italic>\n                  induced persistent pelvic allodynia that was significantly attenuated by microglial depletion (PLX5622) or inhibition (minocycline), indicating a key role for microglia in pain maintenance. In contrast, microglial depletion did not improve urinary dysfunction or anxiety\u2013 and depression-like behaviors. Prefrontal cortex microglia of PUPP mice exhibited reduced microglial branching complexity and a less ramified phenotype, indicative of an activated microglial state. Transcriptomic profiling of brain CD11b+ cells revealed a reactive microglial signature enriched for chemokines, NF\u039aB-related genes, and immediate early response genes, alongside pathways involved in immune regulation and leukocyte recruitment. Both general and microglia-specific TLR4 deletion reduced pelvic allodynia and reduced microglial morphological features of activation. Consistent with this, pharmacological TLR4 inhibition in vitro suppressed LPS-induced NF\u039aB activation, cytokine secretion, and CD68 expression. Together, these findings identify microglial TLR4 as a critical mediator of post-UTI chronic pelvic pain.\n                <\/jats:p>","DOI":"10.64898\/2026.08.04.742321","type":"posted-content","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T01:25:19Z","timestamp":1786411519000},"source":"Crossref","is-referenced-by-count":0,"title":["Microglial TLR4 Mediates Post-UTI Chronic Pelvic Pain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-5270","authenticated-orcid":false,"given":"Habib","family":"Jmii","sequence":"first","affiliation":[{"name":"Department of Urology and Feinberg School of Medicine, Northwestern University, 320 East Superior Street Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivesh","family":"Ghura","sequence":"additional","affiliation":[{"name":"Department of Urology and Feinberg School of Medicine, Northwestern University, 320 East Superior Street Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Department of Urology and Feinberg School of Medicine, Northwestern University, 320 East Superior Street Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Klumpp","sequence":"additional","affiliation":[{"name":"Department of Urology and Feinberg School of Medicine, Northwestern University, 320 East Superior Street Chicago, IL 60611"},{"name":"Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 320 East Superior Street Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081217503385000_2026.08.04.742321v1.1","doi-asserted-by":"publisher","DOI":"10.14670\/HH-18-028"},{"key":"2026081217503385000_2026.08.04.742321v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/srep26083"},{"key":"2026081217503385000_2026.08.04.742321v1.3","doi-asserted-by":"publisher","DOI":"10.5213\/inj.1632522.261"},{"key":"2026081217503385000_2026.08.04.742321v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-014-0908-6"},{"key":"2026081217503385000_2026.08.04.742321v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2011.01.004"},{"key":"2026081217503385000_2026.08.04.742321v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3432"},{"key":"2026081217503385000_2026.08.04.742321v1.7","doi-asserted-by":"crossref","unstructured":"Baars, C. , van Ginkel, C. , Heesakkers, J. , Scholtes, M. , Martens, F. , Janssen, D. , 2023. 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