title: Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC, USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Allen
authors.forename: Mohammed F
authors.initials: MF
authors.lastname: Shamji
authors.forename: Brian A
authors.initials: BA
authors.lastname: Mata
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Gabr
authors.forename: S Michael
authors.initials: SM
authors.lastname: Sinclair
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Schmitt
authors.forename: William J
authors.initials: WJ
authors.lastname: Richardson
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D005684:Gait / Q000187:drug effects / Q000502:physiology; D020233:Gait Disorders, Neurologic / Q000188:drug therapy* / Q000209:etiology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008161:Lumbosacral Region; D008297:Male; D011843:Radiculopathy / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D016474:Weight-Bearing
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha