{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:02:31Z","timestamp":1790190151401,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T00:00:00Z","timestamp":1555286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670688"],"award-info":[{"award-number":["81670688"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800666"],"award-info":[{"award-number":["81800666"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Central sensitization playsimportant roles in cyclophosphamide (CYP)\u2010induced cystitis. In addition, as a visceral pain, CYP\u2010induced chronic pain shares common pathophysiological mechanisms with neuropathic pain. Previous studies demonstrated that neuregulin\u20101 (Nrg1)\u2010ErbB signaling contributes to neuropathic pain, but whether and how this signaling influences mechanical allodynia in CYP\u2010induced cystitis is unclear. This study aimed to determine whether and how Nrg1\u2010ErbB signaling modulates mechanical allodynia in a CYP\u2010induced cystitis rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Systemic injection with CYP was used to establish a rat model of bladder pain syndrome\/interstitial cystitis (BPS\/IC). An irreversible ErbB family receptor inhibitor, PD168393, and exogenous Nrg1 were intrathecally injected to modulate Nrg1\u2010ErbB signaling. Mechanical allodynia in the lower abdomen was assessed with von\u2010Frey filaments using the up\u2010down method. Western blot analysis and immunofluorescence staining were used to measure the expression of Nrg1\u2010ErbB signaling, Iba\u20101, <jats:italic>p<\/jats:italic>\u2010p38, and IL\u20101\u03b2 in the L6\u2010S1 spinal dorsal horn (SDH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed upregulation of Nrg1\u2010ErbB signaling as well as overexpression of the microglia activation markers Iba\u20101 and <jats:italic>p<\/jats:italic>\u2010p38 and the proinflammatory factor, interleukin\u20101\u03b2 (IL\u20101\u03b2), in the SDH of the cystitis group. Further, treatment with PD168393 attenuated mechanical allodynia in CYP\u2010induced cystitis and inhibited microglia activation, leading to decreased production of IL\u20101\u03b2. The inhibitor PD168393 reversed the algesic effect of exogenous Nrg1 on the cystitis model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nrg1\u2010ErbB signaling may promote microglia activation, contributing to mechanical allodynia of CYP\u2010induced cystitis. Our study showed that modulation of Nrg1\u2010ErbB signaling may have therapeutic value for treating pain symptoms in BPS\/IC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24005","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T04:28:22Z","timestamp":1555388902000},"page":"1250-1260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Neuregulin\u20101\u2010ErbB signaling promotes microglia activation contributing to mechanical allodynia of cyclophosphamide\u2010induced cystitis"],"prefix":"10.1002","volume":"38","author":[{"given":"Jia\u2010Liang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pain Research Center and Department of Physiology 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