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Intrathecal resiniferatoxin in a dog model: Efficacy in bone cancer pain

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Intrathecal 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.

RBID : PMC:4431903

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. [11,32] 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. [10,17] 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431903

DOI: 10.1097/j.pain.0000000000000115
PubMed: 25659068
PubMed Central: 4431903

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PMC:4431903

Le document en format XML

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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>
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Intrathecal resiniferatoxin in a dog model: Efficacy in bone cancer pain

Intrathecal resiniferatoxin in a dog model: Efficacy in bone cancer pain

Source :

Abstract

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