Intrathecal Substance P-saporin in the Dog: Efficacy in Bone Cancer Pain

Anesthesiology. 2013 Nov;119(5):1178-85. doi: 10.1097/ALN.0b013e3182a95188.

Abstract

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 study 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 (20-60 µg) in addition to standard-of-care analgesic therapy (n=35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death.

Results: Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 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).

Conclusion: Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Bone Neoplasms / complications*
  • Bone Neoplasms / veterinary*
  • Dog Diseases / drug therapy*
  • Dogs
  • Double-Blind Method
  • Injections, Spinal
  • Lameness, Animal / drug therapy
  • Lameness, Animal / psychology
  • Motor Activity / physiology
  • Pain Measurement / drug effects
  • Pain, Intractable / drug therapy*
  • Pain, Intractable / etiology
  • Pain, Intractable / veterinary*
  • Prospective Studies
  • Ribosome Inactivating Proteins, Type 1 / therapeutic use*
  • Saporins
  • Substance P / analogs & derivatives*
  • Substance P / therapeutic use
  • Treatment Outcome

Substances

  • Ribosome Inactivating Proteins, Type 1
  • substance P-saporin
  • Substance P
  • Saporins