SPCM-01 Characterizing Changes in Ambulatory Function, Mechanosensation, and Distress in a Mouse Model of Metastatic Epidural Spinal Cord Compression.

BACKGROUND Metastatic epidural spinal cord compression (MESCC) can cause severe pain, distress, and ambulatory deficits. However, few studies have investigated the mechanisms or chronologic timing of these functional sequelae. This study aimed to characterize changes in mechanical pain, anxiety, and ambulation that occur in a mouse model of MESCC. After optimization of our MESCC mouse model, behavioral testing was performed to determine the timeline of progression to ambulatory dysfunction, anxiety and pain. METHODS 10,000 Lewis Lung Carcinoma (LLC) cells were implanted intraosseously at the L5 vertebral body of six mice. Mechanical pain, distress and ambulation were tested using the Von Frey filament test, Mouse Grimace Scale (MGS), and balance beam test respectively. Neurologic function was monitored at least three times weekly, and observed changes were noted. RESULTS Three mice died within one day after surgery. Among the three surviving mice, significant ambulatory dysfunction (impaired neurologic function and reduced performance on the balance beam test) occurred between 10-17 days after tumor implantation. MGS scores tended to increase after onset of ambulatory deficits (% change = 246.2), suggesting increased distress. On the Von Frey test, paw withdrawal threshold tended to increase on the side with the most pronounced strength deficits after onset of ambulatory dysfunction (% change = 304.8), suggesting impaired pain sensation on the side most affected. This may be due to tumor infiltration into the lumbar plexus on the side of the lesion. CONCLUSIONS Our preliminary data suggests that decreased mechanosensation and increased distress may occur after significant ambulatory dysfunction is seen in the progression of metastatic spine disease. Histologic analysis of structural changes in bone, muscle, and nerve associated with tumor progression are ongoing. Future studies with larger sample sizes will be conducted to validate these results and compare to non-tumor controls.