GAIT ABNORMALITIES AND SENSORY CHANGES ACCOMPANY NEURO-INFLAMMATION IN ANIMAL MODELS OF DISC HERNIATION RADICULOPATHY

Abstract

Objective: The goal of this study was to evaluate gait and behavioral changes in an animal model of disc-herniation induced radiculopathy. A second objective was to correlate these functional changes to evidence of neuroinflammation and autoreactive lymphocyte immune activation. Methods: The animal model of radiculopathy involved harvesting autologous nucleus pulposus (NP) from a tail intervertebral disc, and then exposing the L5 dorsal root ganglion (DRG) by hemilaminectomy and partial facetectomy. Experimental animals (n = 16) received NP placement onto the DRG andcontrol animals (n = 16) underwent exposure only. At weekly time points, animals were evaluated for mechanical allodynia by Von Frey testing and for gait symmetry by digitized video analysis. At sacrifice, serum was evaluated for inflammatory cytokine content. The L5 DRGs were then evaluated by immunohistochemistry for mediators of inflammation and immune activation. Statistical analyses were at the ? = 0.05 level of significance, with Bonferroni corrections for multiple comparisons when appropriate. Results: Sensory testing revealed persistent mechanical allodynia in rats subjected to NP stimulus compared with the sham surgery group (Von Frey testing, p < 0.01). Gait analysis reflected the functional consequence of this altered sensation revealing marked asymmetry and apreference to place load on the contralateral limb (symmetry index, p < 0.01). Serum cytokine expressionwas equivalent between groups, reaffirming that the sensation and behavioral changes observed in these animals results primarily from local inflammatory changes. Immunohistochemicalanalysis of the sectioned DRGs after sacrifice revealed equivalent post-surgical inflammatory activation (IL23, p = 0.47), but substantial immuneactivation in the NP group (IL17, p = 0.01). Conclusion: This model of radiculopathy provides the first evidence of altered gait symmetry and locomotor ability in animals subjected to non-compressive placement of NP tissue. Systemic inflammation was absent as expected, but mechanical allodynia, local inflammation, and autoreactive immune activation were observed. Future work involves therapeutic interventions targeting these changes to rescue animals from the phenotype of inflammatory radiculopathy.