Intrathecal resiniferatoxin in a dog model: Efficacy in bone cancer pain
Identifieur interne : 001159 ( Pmc/Checkpoint ); précédent : 001158; suivant : 001160Intrathecal resiniferatoxin in a dog model: Efficacy in bone cancer pain
Auteurs : Dorothy Cimino Brown [États-Unis] ; Kimberly Agnello [États-Unis] ; Michael J. Iadarola [États-Unis]Source :
- Pain [ 0304-3959 ] ; 2015.
Abstract
Resiniferatoxin (RTX) is the most potent amongst all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium permeable non-selective cation channel, expressed on the peripheral and central terminals of small diameter sensory neurons. [
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DOI: 10.1097/j.pain.0000000000000115
PubMed: 25659068
PubMed Central: 4431903
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<front><div type="abstract" xml:lang="en"><p id="P1">Resiniferatoxin (RTX) is the most potent amongst all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium permeable non-selective cation channel, expressed on the peripheral and central terminals of small diameter sensory neurons. [<xref rid="R11" ref-type="bibr">11</xref>
,<xref rid="R32" ref-type="bibr">32</xref>
] Prolonged calcium influx induced by RTX causes cytotoxicity and death of only those sensory neurons that express the TRPV1 ion channel leading to selective targeting and permanent deletion of the TRPV1-expressing C-fiber neuronal cell bodies in the dorsal root ganglia. [<xref rid="R10" ref-type="bibr">10</xref>
,<xref rid="R17" ref-type="bibr">17</xref>
] The goal of this project was to provide pre-clinical efficacy data, that intrathecal RTX could provide effective pain relief and improve function in dogs with bone cancer without significant long-term side effects. In a single blind, controlled study, 72 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n=36) or 1.2 mcg/kg intrathecal RTX in addition to standard of care analgesic therapy (treated, n=36). Significantly more dogs in the control group (78%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with RTX (50%; p<0.03); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with RTX (p<0.02). The analgesic effect was documented in these dogs without any evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies.</p>
</div>
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<title-group><article-title>Intrathecal resiniferatoxin in a dog model: Efficacy in bone cancer pain</article-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Brown</surname>
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University of Pennsylvania, School of Veterinary Medicine, Department of Clinical Studies, 3900 Delancey Street, Philadelphia, PA 19104-6010, USA</aff>
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Neuronal Gene Expression Unit, Pain and Neurosensory Mechanisms Branch, NIDCR Building 49, Room 1A11, 49 Convent Drive, MSC 4410, Bethesda, MD 20892-4410, USA</aff>
<author-notes><corresp id="FN1">Corresponding Author: Dorothy Cimino Brown, D.V.M., Department of Clinical Studies - Philadelphia, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, Philadelphia, PA 19104-6010, 215-898-0030 (Phone), <email>dottie@vet.upenn.edu</email>
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<pub-date pub-type="nihms-submitted"><day>30</day>
<month>1</month>
<year>2015</year>
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<pub-date pub-type="ppub"><month>6</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>6</month>
<year>2016</year>
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<volume>156</volume>
<issue>6</issue>
<fpage>1018</fpage>
<lpage>1024</lpage>
<pmc-comment>elocation-id from pubmed: 10.1097/j.pain.0000000000000115</pmc-comment>
<abstract><p id="P1">Resiniferatoxin (RTX) is the most potent amongst all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium permeable non-selective cation channel, expressed on the peripheral and central terminals of small diameter sensory neurons. [<xref rid="R11" ref-type="bibr">11</xref>
,<xref rid="R32" ref-type="bibr">32</xref>
] Prolonged calcium influx induced by RTX causes cytotoxicity and death of only those sensory neurons that express the TRPV1 ion channel leading to selective targeting and permanent deletion of the TRPV1-expressing C-fiber neuronal cell bodies in the dorsal root ganglia. [<xref rid="R10" ref-type="bibr">10</xref>
,<xref rid="R17" ref-type="bibr">17</xref>
] The goal of this project was to provide pre-clinical efficacy data, that intrathecal RTX could provide effective pain relief and improve function in dogs with bone cancer without significant long-term side effects. In a single blind, controlled study, 72 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n=36) or 1.2 mcg/kg intrathecal RTX in addition to standard of care analgesic therapy (treated, n=36). Significantly more dogs in the control group (78%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with RTX (50%; p<0.03); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with RTX (p<0.02). The analgesic effect was documented in these dogs without any evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies.</p>
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