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Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism.
Abstract
Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of
lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior
studies have demonstrated that TNF antagonists can attenuate heightened nociception
resulting from lumbar radiculopathy in the preclinical model. Less is known about
the potential impact of TNF antagonism on gait compensations, despite being of clinical
relevance. In this study, we expand on previous descriptions of gait compensations
resulting from lumbar radiculopathy in the rat and describe the ability of local TNF
antagonism to prevent the development of gait compensations, altered weight bearing,
and heightened nociception.Eighteen male Sprague-Dawley rats were investigated for
mechanical sensitivity, weight-bearing, and gait pre- and post-operatively. For surgery,
tail nucleus pulposus (NP) tissue was collected and the right L5 dorsal root ganglion
(DRG) was exposed (Day 0). In sham animals, NP tissue was discarded (n = 6); for experimental
animals, autologous NP was placed on the DRG with or without 20 μg of soluble TNF
receptor type II (sTNFRII, n = 6 per group). Spatiotemporal gait characteristics (open
arena) and mechanical sensitivity (von Frey filaments) were assessed on post-operative
Day 5; gait dynamics (force plate arena) and weight-bearing (incapacitance meter)
were assessed on post-operative Day 6.High-speed gait characterization revealed animals
with NP alone had a 5% decrease in stance time on their affected limbs on Day 5 (P
≤0.032). Ground reaction force analysis on Day 6 aligned with temporal changes observed
on Day 5, with vertical impulse reduced in the affected limb of animals with NP alone
(area under the vertical force-time curve, P <0.02). Concordant with gait, animals
with NP alone also had some evidence of affected limb mechanical allodynia on Day
5 (P = 0.08) and reduced weight-bearing on the affected limb on Day 6 (P <0.05). Delivery
of sTNFRII at the time of NP placement ameliorated signs of mechanical hypersensitivity,
imbalanced weight distribution, and gait compensations (P <0.1).Our data indicate
gait characterization has value for describing early limb dysfunctions in pre-clinical
models of lumbar radiculopathy. Furthermore, TNF antagonism prevented the development
of gait compensations subsequent to lumbar radiculopathy in our model.
Type
Journal articleSubject
Lumbosacral RegionAnimals
Rats
Rats, Sprague-Dawley
Gait Disorders, Neurologic
Hyperalgesia
Radiculopathy
Disease Models, Animal
Tumor Necrosis Factor-alpha
Receptors, Tumor Necrosis Factor, Type II
Gait
Adaptation, Physiological
Weight-Bearing
Male
Biomechanical Phenomena
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https://hdl.handle.net/10161/18593Published Version (Please cite this version)
10.1186/ar3451Publication Info
Allen, Kyle D; Shamji, Mohammed F; Mata, Brian A; Gabr, Mostafa A; Sinclair, S Michael;
Schmitt, Daniel O; ... Setton, Lori A (2011). Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and
the effects of tumor necrosis factor-alpha antagonism. Arthritis research & therapy, 13(4). pp. R137. 10.1186/ar3451. Retrieved from https://hdl.handle.net/10161/18593.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Mostafa Gabr
Research Associate, Senior
Dr. Gabr's research has specifically focused on the following broad areas: (i) animal
model of myelopathy, (ii) participating in clinical trials in spine field.In the last
few years, this research agenda has expanded to include collaborative projects and
publications. Dr. Gabr and his colleagues explore benefit of cervical collar following
spine fusion, spinal cord injury model, and transforaminal lumbar interbody fusion.Dr.
Gabr is the author of "Interleukin-17 synergizes with IFNI&
Daniel Oliver Schmitt
Professor in the Department of Evolutionary Anthropology
My primary interest is in the evolution of primate locomotion. I am studying the
mechanics of movement in primates and other vertebrates in the laboratory to understand
the relationship between movement and postcranial morphology, and the unique nature
of primates among mammals. Current projects include the origins of primate locomotion
and the evolution of vertebrate bipedalism.
Lori A. Setton
Adjunct Professor of Biomedical Engineering
Research in Setton's laboratory is focused on the role of mechanical factors in the
degeneration and repair of soft tissues of the musculoskeletal system, including the
intervertebral disc, articular cartilage and meniscus. Work in the Laboratory is focused
on engineering and evaluating materials for tissue regeneration and drug delivery.
Studies combining engineering and biology are also used to determine the role of mechanical
factors to promote and control healing of cartilaginous tissues. Re
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