Effects of Targeted Proton Radiation on Spinal Cord in a Porcine Model: A Pilot Study

Aim: To determine whether proton radiation can be used to treat chronic intractable pain. The focus of this study was on the biological effects of spinal cord irradiation. Materials and Methods: Proton radiation (0-25 Gy, single fraction) was applied to the spinal cord within L3-L5 of Yucatan mini-pigs (n=20). Skin reaction, body mass and behavior were monitored. At euthanasia, blood and spinal cord were analyzed. Results: Skin morbidity was mild and overall health for the 5-20 Gy-treated groups was good based on behavior and weight gain up to 8.5-9 months postexposure. The 25 Gy-treated animals developed hind limb weakness at 2.5-3 months and were euthanized. Radiation had a significant effect on white blood cell count (p<0.05), with the 25 Gy-treated mini-pigs having the highest number of all three major leukocyte populations. A few differences were also noted for erythrocyte parameters, but the blood chemistry panel was normal. Apoptosis in the targeted portion of the spinal cord was elevated in the 20-and 25 Gy-treated groups versus 0 Gy (p<0.05) based on the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. There was a trend (p<0.1) for a radiation effect on glial fibrillary acidic protein expression, with the highest value being found after 25 Gy. Histology showed no difference between 0 versus 25 Gy. Conclusion: The data demonstrated that a small segment of the spinal cord can be readily targeted using proton radiation; doses ranging from 5-20 Gy were well-tolerated in an animal model with radiosensitivity similar to humans. Future studies with a pain model should use <= 15 Gy.