Assessing Anxiety and Distress in an Orthotopic Epidural Spinal Cord Compression Model: A Pilot Study

Introduction: Metastatic epidural spinal cord compression (MESCC) occurs in 5-10% of patients with spinal cord metastases and can cause significant disability and distress. This study aimed to establish a mouse model of MESCC and measure changes in anxiety and distress as MESCC develops. This pilot study will help guide a future study using neuromonitoring to identify neural networks involved in psychological distress in a mouse model of MESCC.

Methods: Lewis lung carcinoma (LLC) cells (25,000 cell/3 microliters) were implanted intra-osseously into lumbar vertebrae of three C57BL6 mice to induce MESCC. Anxiety was assessed using the open field test and the Mouse Grimace Scale (MGS) at baseline and at various timepoints post-operatively. When endpoints were reached, tumor and spinal cord tissue was harvested for histological analysis.

Results: On the open field test, mice spent significantly more time in the margin of the field post-operatively (mean = 245 ± 35.20 s) compared to baseline (mean = 207.1 ± 28.56 s) (p < 0.001) and spent significantly more time exhibiting stereotypy behavior post-operatively (mean = 20.23 ± 5.20 s) compared to baseline (mean = 13.79 ± 6.56 s) (p < 0.001), indicating increased anxiety after surgery. MGS scores also tended to increase a mice got further out from surgery, indicating increased spontaneous pain and distress, however these results were not significant. Tumors grew quickly, and all mice died or were euthanized by day 16. Histological analysis showed tumor infiltration into the spinal cord in two mice. Nerve root compression was seen in all mice.

Conclusion : MESCC was successfully achieved in two out of three mice. Mice exhibited increased anxiety post-operatively compared to baseline. In future studies, fewer LLC cells may be used to induce MESCC and allow for prolonged survival of mice for additional behavioral testing.