title: Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model.
abstract: BACKGROUND
  Resiniferatoxin is a potent capsaicin analog. Intrathecal administration leads to selective, prolonged opening of the transient receptor potential V1 ion channel, which is localized mainly to C-fiber primary afferent nociceptive sensory neurons. Following work in laboratory animals, the authors explored the use of intrathecal resiniferatoxin to control spontaneous bone cancer pain in companion (pet) dogs.
  
  
  METHODS
  Normal canine population: Behavioral testing was performed to establish baseline paw withdrawal latency; subsequently, general anesthesia was induced and resiniferatoxin was administered intrathecally while hemodynamic parameters were recorded. Behavior testing was repeated for 12 days after administration of resiniferatoxin. Clinical canine population: Twenty companion dogs with bone cancer pain were recruited. The animal's baseline level of discomfort and analgesic use were recorded. Resiniferatoxin was administered intrathecally and hemodynamic parameters were monitored while the dogs were under general anesthesia. Dogs were reevaluated up to 14 weeks after resiniferatoxin administration.
  
  
  RESULTS
  Normal canine population: In the first minutes after resiniferatoxin injection, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate from baseline. Two days after injection, limb withdrawal latencies increased to the point of cutoff in the dogs that received at least 1.2 microg/kg resiniferatoxin. Clinical canine population: From baseline, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate after resiniferatoxin injection. Comfort scores were significantly improved at 2, 6, 10, and 14 weeks after resiniferatoxin administration (P < 0.0001). There was decreased or discontinued use of supplemental analgesics in 67% of the dogs 2 weeks after resiniferatoxin administration.
  
  
  CONCLUSIONS
  Intrathecal resiniferatoxin elicits transient hemodynamic effects. In controls, a profound and sustained blockade of thermal stimuli is produced in a dose-dependent fashion. Similar administration in dogs with bone cancer produces a prolonged antinociceptive response.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6010, USA. dottie@vet.upenn.edu
authors.forename: Dorothy Cimino
authors.initials: DC
authors.lastname: Brown
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Iadarola
authors.forename: Sandra Z
authors.initials: SZ
authors.lastname: Perkowski
authors.forename: Hardam
authors.initials: H
authors.lastname: Erin
authors.forename: Frances
authors.initials: F
authors.lastname: Shofer
authors.forename: Karai J
authors.initials: KJ
authors.lastname: Laszlo
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Olah
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mannes
mesh_terms: D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications* / Q000473:pathology / Q000662:veterinary*; D002404:Catheterization; D015331:Cohort Studies; D004224:Diterpenes / Q000009:adverse effects / Q000494:pharmacology*; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007278:Injections, Spinal; D010146:Pain / Q000188:drug therapy* / Q000662:veterinary*; D010147:Pain Measurement / Q000187:drug effects
chemical_list: D000700:Analgesics; D004224:Diterpenes; C024353:resiniferatoxin