title: Intrathecal substance P-saporin in the dog: efficacy in bone cancer pain.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: * Professor of Surgery, † Assistant Professor of Surgery, Department of Clinical Studies - Philadelphia, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania.
authors.forename: Dorothy Cimino
authors.initials: DC
authors.lastname: Brown
authors.forename: Kimberly
authors.initials: K
authors.lastname: Agnello
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001859:Bone Neoplasms / Q000150:complications* / Q000662:veterinary*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004311:Double-Blind Method; D007278:Injections, Spinal; D007794:Lameness, Animal / Q000188:drug therapy / Q000523:psychology; D009043:Motor Activity / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology / Q000662:veterinary*; D011446:Prospective Studies; D054789:Ribosome Inactivating Proteins, Type 1 / Q000627:therapeutic use*; D000076985:Saporins; D013373:Substance P / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D054789:Ribosome Inactivating Proteins, Type 1; C468274:substance P-saporin; D013373:Substance P; D000076985:Saporins