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).

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.

• Authors: Dorothy Cimino Brown, Kimberly Agnello
• Journal: Anesthesiology (Anesthesiology) Vol. 119 Issue 5 Pg. 1178-85 (Nov 2013) ISSN: 1528-1175 [Electronic] United States
• PMID: 24195949 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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