Safety Evaluation of Intrathecal Substance P-Saporin, a Targeted Neurotoxin, in Dogs

targeted neurotoxin, produces selective destruction of superficial neurokinin 1 receptor (NK1r)–bearing cells in the spinal dorsal horn. In rats, SP-SAP prevents the formation of hyperalgesia and can reverse established neuropathic pain behavior in rodents. To determine the safety of this therapeutic modality in a large animal model, beagles received bolus IT lumbar injections of vehicle, SP-SAP (1.5, 15, 45, or 150 mg), or a nontargeted preparation of saporin (SAP, 150 mg) for immunohistological analysis of spinal cords. Doses of 15 mg SP-SAP and above produced a significant and equivalent loss of NK1r-bearing cells and dendrites in lumbar laminae II and I compared to vehicle- or SAP-treated animals. Cervical regions in all animals displayed no loss of NK1r immunoreactivity as compared to controls. Total numbers of neu-rons in the lumbar dorsal horn or alpha-motor neurons in the ventral horn demonstrated no significant changes. No increases i