Gait Abnormalities and Inflammatory Cytokines in an Autologous Nucleus Pulposus Model of Radiculopathy

The authors investigated gait abnormalities and mechanical hypersensitivity associated with invertebral disc herniation in a rat model of radiculopathy. Further evaluation involved assessing how nucleus pulposus (NP) injury affected systemic cytokine expression and molecular changes at the dorsal ro...

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Published in:Spine (Philadelphia, Pa. 1976) Pa. 1976), 2009-04, Vol.34 (7), p.648-654
Main Authors: SHAMJI, Mohammed F, ALLEN, Kyle D, RICHARDSON, William J, SO, Stephen, LIUFANG JING, ADAMS, Samuel B, SCHUH, Reinhard, HUEBNER, Janet, KRAUS, Virginia B, FRIEDMAN, Allan H, SETTON, Lori A
Format: Article
Language:English
Subjects:
Animals
Autoantibodies - metabolism
Autoantigens - metabolism
Autoimmune Diseases - immunology
Autoimmune Diseases - pathology
Autoimmune Diseases - physiopathology
Biological and medical sciences
Cerebrospinal fluid. Meninges. Spinal cord
Cytokines - analysis
Cytokines - blood
Disease Models, Animal
Fibrocartilage - immunology
Fibrocartilage - pathology
Fibrocartilage - physiopathology
Ganglia, Spinal - immunology
Ganglia, Spinal - pathology
Ganglia, Spinal - physiopathology
Hyperalgesia - immunology
Hyperalgesia - physiopathology
Inflammation - blood
Inflammation - immunology
Inflammation - physiopathology
Inflammation Mediators - metabolism
Intervertebral Disc - immunology
Intervertebral Disc - pathology
Intervertebral Disc - physiopathology
Intervertebral Disc Displacement - immunology
Intervertebral Disc Displacement - pathology
Intervertebral Disc Displacement - physiopathology
Lameness, Animal - etiology
Lameness, Animal - pathology
Lameness, Animal - physiopathology
Lumbar Vertebrae - pathology
Male
Medical sciences
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Nervous system (semeiology, syndromes)
Neurology
Radiculopathy - immunology
Radiculopathy - pathology
Radiculopathy - physiopathology
Rats
Rats, Sprague-Dawley
Transplantation, Autologous - methods
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Summary:The authors investigated gait abnormalities and mechanical hypersensitivity associated with invertebral disc herniation in a rat model of radiculopathy. Further evaluation involved assessing how nucleus pulposus (NP) injury affected systemic cytokine expression and molecular changes at the dorsal root ganglion (DRG). The objective of this work was to describe the gait and behavioral changes in an animal model of disc-herniation induced radiculopathy. A second objective included examining how these functional changes correlated with neuroinflammation and autoreactive lymphocyte immune activation. Animal models of radiculopathy describe demyelination, slowed nerve conduction, and heightened pain sensitivity after application of autologous NP to the DRG. The quantitative impact of disc herniation on animal locomotion has not been investigated. Further, while local inflammation occurs at the injury site, the role of autoimmune cytokines reactive against previously immune-sequestered NP requires investigation. NP-treated animals (n = 16) received autologous tail NP placed onto the L5 DRG exposed by unilateral facetectomy, and control animals (n = 16) underwent exposure only. At weekly time points, animals were evaluated for mechanical allodynia, thermal hyperalgesia, and gait characteristics through digitized video analysis. Serum cytokine content was measured after animal sacrifice, and immunohistochemistry tested DRG tissue for mediators of inflammation and immune activation. Sensory testing revealed mechanical allodynia in the affected limb of NP-treated rats compared with sham animals (P < 0.01) at all time points. Gait analysis reflected functional locomotive consequences of marked asymmetry (P = 0.048) and preference to bear weight on the contralateral limb (duty factor imbalance, P < 0.01) at early time points. Equivalent serum cytokine expression occurred in both groups, confirming the local inflammatory nature of this disease model. Immunohistochemistry of the sectioned DRGs revealed equivalent postsurgical inflammatory activation (interleukin 23, P = 0.47) but substantial early immune activation in the NP-treated group (interleukin 17, P = 0.01). This model of radiculopathy provides evidence of altered gait in a model of noncompressive disc herniation. Systemic inflammation was absent, but mechanical allodynia, local inflammation, and autoreactive immune activation were observed. Future work will involve therapeutic interventions to rescue animals fro
ISSN:0362-2436
1528-1159
DOI:10.1097/BRS.0b013e318197f013