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Intrathecal resiniferatoxin in a dog model

efficacy in bone cancer pain

Brown, Dorothy C.a,*; Agnello, Kimberlya; Iadarola, Michael J.b

doi: 10.1097/j.pain.0000000000000115
Research Paper
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Resiniferatoxin (RTX) is the most potent among all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium-permeable nonselective cation channel, expressed on the peripheral and central terminals of small-diameter sensory neurons. 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. The goal of this project was to provide preclinical 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 μg/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.

Intrathecal resiniferatoxin provides effective pain relief in a naturally occurring canine bone cancer model without occurrence of self-mutilation, which can be indicative of deafferentation pain.

aDepartment of Clinical Studies, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA, USA

bAnesthesia Section, Department of Perioperative Medicine, Clinical Center, NIH, Bethesda, MD, USA

Corresponding author. Address: Department of Clinical Studies, Philadelphia, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey St, Philadelphia, PA 19104-6010, USA. Tel.: 215-898-0030. E-mail address: dottie@vet.upenn.edu (D. C. Brown).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received September 30, 2014

Received in revised form January 13, 2015

Accepted January 27, 2015

© 2015 International Association for the Study of Pain
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