{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T08:28:20Z","timestamp":1769502500003,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T00:00:00Z","timestamp":1398211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Botulinum toxin <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>nabot\/<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>) has been shown to have an antinociceptive effect. This might be due to an impairment of sensory nerves not only in the peripheral but also in the central nervous system. In this work, we analysed both systems by studying the effect of intrathecal (i.t.) administration of botulinum toxin <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> in an animal model of bladder pain and hyperactivity induced by cyclophosphamide (<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats were implanted with an i.t. catheter at the <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>6 segment. Bladder pain was induced by intraperitoneal (i.p.) injection of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>. Five experimental groups were created: (1) Saline i.p.\u2009+\u2009i.t.; (2) Onabot\/<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> i.t.; (3) <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content> i.p.\u2009+\u2009saline i.t.; (4) <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content> i.p.\u2009+\u2009<jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>nabot\/<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> i.t. 48\u2009h after <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>; and (5) <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>nabot\/<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> i.t. 30 days. Mechanical sensitivity was assessed in the abdomen and hindpaws. Motor activity was observed in an open\u2010field arena. Bladder reflex activity was evaluated by cystometry. At the end, bladders and spinal cord were immunoreacted (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>) against cleaved <jats:styled-content style=\"fixed-case\">SNAP<\/jats:styled-content>\u201025 (<jats:styled-content style=\"fixed-case\">cSNAP<\/jats:styled-content>\u201025), c\u2010<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>os, p\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>, calcitonin gene\u2010related peptide (<jats:styled-content style=\"fixed-case\">CGRP)<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GAP<\/jats:styled-content>43.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The toxin reduced pain symptoms, bladder hyperactivity, expression of neuronal activation markers and <jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>, typically up\u2010regulated in this inflammatory model. The presence of <jats:styled-content style=\"fixed-case\">cSNAP<\/jats:styled-content>\u201025 was detected in the spinal cord and bladder fibres from animals treated with <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>nabot\/<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>. No somatic or visceral motor impairments were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that i.t. <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>nabot\/<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> has a strong analgesic effect in a model of severe bladder pain. This route of administration can be further explored to treat intractable forms of pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.513","type":"journal-article","created":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T10:19:12Z","timestamp":1398248352000},"page":"1480-1489","source":"Crossref","is-referenced-by-count":39,"title":["Intrathecal administration of botulinum toxin type <scp>A<\/scp> improves urinary bladder function and reduces pain in rats with cystitis"],"prefix":"10.1002","volume":"18","author":[{"given":"A.","family":"Coelho","sequence":"first","affiliation":[{"name":"Department of Experimental Biology Faculty of Medicine University of Porto  Portugal"},{"name":"IBMC Instituto for Molecular and Cell Biology University of Porto  Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology Faculty of Medicine University of Porto  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