Medical Student Department of Neurosurgery, Duke University School of Medicine, Durham, NC Durham, NC, US
Introduction: Although epidural spinal cord compression (ESCC) can cause significant pain and distress, few studies have investigated mechanisms of ESCC-induced pain or anxiety. This study aimed to establish a mouse model of ESCC and measure changes in nociception and anxiety as ESCC develops.
Methods: Lewis lung carcinoma cells were implanted intra-osseously into lumbar vertebrae of three mice. Mechanosensation and thermosensation were assessed using the Von Frey filament, hot plate, and tail flick tests. Anxiety was assessed using the open field test and the Mouse Grimace Scale (MGS). Tumor and spinal cord tissue were harvested for histological analysis at endpoint.
Results: Von Frey responses reduced by 60.0% in the left paw and 62.5% in the right paw post-operatively compared to baseline, indicating reduced mechanosensation. However, these differences could not be statistically assessed as only one mouse survived to the final timepoint. Mice exhibited longer response times on the tail flick test (% change = 24.8%, p = 0.08) and the hot plate test (% change = 18.1%, n.s.) post-operatively, indicating reduced thermosensation. On the open field test, mice spent more time in the margin post-operatively (mean = 245 +/- 35.20 s) compared to baseline (mean = 207.1 +/- 28.56 s) (p < 0.001) and spent 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 trended upward post-operatively, indicating increased spontaneous pain and distress (n.s.). Histology showed spinal cord compression in two mice and nerve root compression in all mice.
Conclusion : Mice trended toward reduced nociception and exhibited increased anxiety post-operatively. While this feasibility study is limited in power, future studies will incorporate a larger sample size and use fewer tumor cells to improve survival and facilitate additional behavioral testing.
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