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We examined the effects of epidural administration of the P<\/jats:styled-content>\/Q<\/jats:styled-content>\u2010 and N<\/jats:styled-content>\u2010type VGCC<\/jats:styled-content> blockers T<\/jats:styled-content>x3\u20103 and P<\/jats:styled-content>h\u03b11\u03b2, respectively, isolated from the spider P<\/jats:italic><\/jats:styled-content>honeutria nigriventer<\/jats:italic>, on symptomatic, inflammatory and functional changes allied to mouse cyclophosphamide (CPA<\/jats:styled-content>)\u2010induced haemorrhagic cystitis (HC<\/jats:styled-content>). The effects of P<\/jats:italic><\/jats:styled-content>.\u2009nigriventer<\/jats:italic>\u2010derived toxins were compared with those displayed by MVIIC<\/jats:styled-content> and MVIIA<\/jats:styled-content>, extracted from the cone snail Conus<\/jats:italic><\/jats:styled-content>\u2009magus<\/jats:italic>.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>HC<\/jats:styled-content> was induced by a single i.p. injection of CPA<\/jats:styled-content> (300\u2009mg\u00b7kg\u20131<\/jats:sup>). Dose\u2010 and time\u2010related effects of spinally administered P<\/jats:styled-content>\/Q and N<\/jats:styled-content>\u2010type VGCC<\/jats:styled-content> blockers were assessed on nociceptive behaviour and macroscopic inflammation elicited by CPA<\/jats:styled-content>. The effects of toxins were also evaluated on cell migration, cytokine production, oxidative stress, functional cystometry alterations and TRPV1<\/jats:styled-content>, TRPA1<\/jats:styled-content> and NK1<\/jats:sub><\/jats:styled-content> receptor mRNA<\/jats:styled-content> expression.<\/jats:p><\/jats:sec>Key Results<\/jats:title>The spinal blockage of P<\/jats:styled-content>\/Q<\/jats:styled-content>\u2010type VGCC<\/jats:styled-content> by T<\/jats:styled-content>x3\u20103 and MVIIC<\/jats:styled-content> or N<\/jats:styled-content>\u2010type VGCC<\/jats:styled-content> by Ph\u03b11\u03b2 attenuated nociceptive and inflammatory events associated with HC<\/jats:styled-content>, including bladder oxidative stress and cytokine production. CPA<\/jats:styled-content> produced a slight increase in bladder TRPV1<\/jats:styled-content> and TRPA1 mRNA<\/jats:styled-content> expression, which was reversed by all the toxins tested. Noteworthy, P<\/jats:styled-content>h\u03b11\u03b2 strongly prevented bladder neutrophil migration, besides HC<\/jats:styled-content>\u2010related functional alterations, and its effects were potentiated by co\u2010injecting the selective NK1<\/jats:sub> receptor antagonist CP<\/jats:styled-content>\u201096345.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>Our results shed new light on the role of spinal P<\/jats:styled-content>\/Q<\/jats:styled-content> and N<\/jats:styled-content>\u2010type VGCC<\/jats:styled-content> in bladder dysfunctions, pointing out P<\/jats:styled-content>h\u03b11\u03b2 as a promising alternative for treating complications associated with CPA<\/jats:styled-content>\u2010induced HC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12966","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T02:40:44Z","timestamp":1412822444000},"page":"924-939","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Spinal blockage of P<\/scp>\/Q<\/scp>\u2010 or N<\/scp>\u2010type voltage\u2010gated calcium channels modulates functional and symptomatic changes related to haemorrhagic cystitis in mice"],"prefix":"10.1111","volume":"172","author":[{"given":"R B M","family":"Silva","sequence":"first","affiliation":[{"name":"Postgraduate Program in Medicine and Health Sciences Pontifical Catholic University of Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil"},{"name":"Institute of Toxicology and Pharmacology Pontifical Catholic University of Rio Grande do Sul Porto Alegre Rio Grande do Sul 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