Time-Dependent Mechanics and Measures of Glial Activation and Behavioral Sensitivity in a Rodent Model of Radiculopathy

Abstract

Nerve root compression induces persistent behavioral hypersensitivity and spinal glial reactivity. Viscoelastic properties of neural tissues suggest that physiologic outcomes may depend on the duration of an applied nerve root compression. This study evaluated the time-dependent properties of the root under compression in the context of pain-related behavioral and physiologic outcomes. The decrease in applied load measured by load relaxation under compression was quantified for rat cervical (C6-C8) roots in situ for durations of 30 sec, 3 min, or 15 min (n = 6). Immediately following compression, the change in the root width relative to its original width was quantified as a measure of its structural recovery. Both load relaxation and structural recovery were significantly (p < 0.05) correlated with duration of compression. After 30 sec of compression, load relaxed by 22 +/- 10%; increasing to 36 +/- 18% and 56 +/- 20% at 3 and 15 min, respectively. Following 30 sec, 3 min, and 15 min of compression, the root recovered to 91 +/- 5%, 88 +/- 5 and 72 +/- 13% of its original width, respectively. A companion in vivo study imposed these same compression durations and sham procedures to the C7 root to evaluate pain symptoms and spinal glial reactivity. Allodynia was assessed for 7 days to measure behavioral sensitivity. Immunohistochemistry and quantitative densitometry detected GFAP and OX-42 in the dorsal horn at day 7. Significant correlations were detected between compression duration and allodynia (p < 0.03), and astrocyte and microglial activation (p < 0.01). These biomechanical and glial results imply that a similar duration of compression may modulate both sustained pain and spinal glial reactivity.