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.
BackgroundPrimary hyperaldosteronism (PHA) in cats occurs as a consequence of excessive hormone production by an adrenocortical tumor. Median survival time, association between tumor type and prognosis, and the likelihood that cats require continued medical therapy after surgery have not been systematically evaluated.ObjectivesTo determine the median survival time of cats with PHA treated by unilateral adrenalectomy. To examine if tumor type, anesthesia time, or tumor location (left or right side) affect survival and if affected cats require continued postoperative treatment for persistent hypertension or hypokalemia.AnimalsTen client‐owned cats.MethodsRetrospective study. Cats were diagnosed with PHA based on clinical signs, increased plasma aldosterone concentration, and advanced imaging. Cats underwent unilateral adrenalectomy. Survival time (days alive after surgery) was determined for each cat. Factors affecting median survival time were investigated, including histopathology, anesthesia time, and location (side) of the tumor.ResultsEight of 10 cats survived to discharge from the hospital post adrenalectomy. Overall median survival was 1,297 days (range 2–1,582 days). The only significant factor affecting median survival time was anesthesia time >4 hours. Tumor type and location (side) did not significantly affect median survival time. No cats required continued medical treatment for PHA.Conclusions and Clinical ImportanceAlthough PHA in cats is still considered an uncommon condition, it should be considered in middle to older aged cats with hypokalemic polymyopathy and systemic hypertension. Surgical correction by unilateral adrenalectomy is a viable approach to definitive treatment of PHA with no need for continued medical management.
The SPA laparoscopic entry technique can be used in dogs, although instrument and camera interference can occur if trocar placement is too consolidated within the initial skin incision.
Background Substance-p saporin (SP-SAP), a chemical conjugate of substance-p and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin 1 receptor bearing cells in the spinal dorsal horn. The goal of this project was to provide proof of concept data, that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs. Methods In a single blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n=35) or intrathecal SP-SAP (20-60μg) in addition to standard of care analgesic therapy (n=35). Activity, pain scores, and videography data was collected at baseline, 2 weeks post randomization, and then monthly until death. Results While the efficacy results at the 2-week post randomization point were equivocal, the outcomes evaluated beyond two weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with SP-SAP (24%; p<0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (p<0.01). Conclusions Intrathecal SP-SAP administration in dogs with bone cancer produces a time dependent anti-nociceptive effect with no evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies.
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