Luger NM, Sabino MC, Schwei MJ, Rogers SD, Pomonis JD, Keyser CP, Mach DB, Salak-Johnson J, Clohisy DR, Mantyh PW (2001) Intrathecal infusion of substance P-saporin ablates substance p receptor expressing neurons in the dorsal horn of the spinal cord and attenuates bone cancer pain. Neuroscience 2001 Abstracts 55.4. Society for Neuroscience, San Diego, CA.
Summary: Over 75% of advanced cancer patients must cope with chronic cancer pain. Interestingly, bone cancer pain is the most common and difficult to control. While current therapies are effective in alleviating many aspects of bone cancer pain, they are often accompanied by significant unwanted side effects. To better understand the population of spinal cord neurons that are involved in conveying bone cancer pain and to determine the efficacy of a novel therapeutic modality, we ablated substance P receptor (SPR)+ neurons in the spinal cord using intrathecal infusion of substance P-Saporin (SP-SAP). SP-SAP is a suicide ligand which consists of the ribosomal inactivating factor saporin conjugated to substance P, a peptidergic neurotransmitter involved in nociception. SP-SAP selectively ablates SPR+ neurons located in lamina I and III-V of the spinal cord. C3H male mice received intrathecal SP-SAP treatment 30 days prior to injection of 2472 osteosarcoma cells into the intramedulary space of a femur. Following injection, osteolytic sarcoma cells were confined within the femur by an amalgam plug. Mice were behaviorally tested 17 days post-tumor implantation and both ongoing and movement-evoked pain assessed. Ablation of SPR+ neurons in the dorsal spinal cord coincided with attenuation of both spontaneous and movement-evoked pain behaviors. These results suggest that SPR expressing neurons are involved in the development and progression of the bone cancer pain state and SP-SAP may serve as a useful therapy to treat this debilitating condition. Supported by NIH & VA.
Related Products: SP-SAP (Cat. #IT-07)