title: Simulated whiplash modulates expression of the glutamatergic system in the spinal cord suggesting spinal plasticity is associated with painful dynamic cervical facet loading.
abstract: The cervical facet joint and its capsule have been reported to be injured during whiplash scenarios and are a common source of chronic neck pain from whiplash. Both the metabotropic glutamate receptor 5 (mGluR5) and the excitatory amino acid carrier 1 (EAAC1) have pivotal roles in chronic pain. In this study, spinal mGluR5 and EAAC1 were quantified following painful facet joint distraction in a rat model of facet-mediated painful loading and were evaluated for their correlation with the severity of capsule loading. Rats underwent either a dynamic C6/C7 joint distraction simulating loading experienced during whiplash (distraction; n = 12) or no distraction (sham; n = 6) to serve as control. The severity of capsular loading was quantified using strain metrics, and mechanical allodynia was assessed after surgery. Spinal cord tissue was harvested at day 7 and the expression of mGluR5 and EAAC1 were quantified using Western blot analysis. Mechanical allodynia following distraction was significantly (p < 0.001) higher than sham. Spinal expression of mGluR5 was also significantly (p < 0.05) greater following distraction relative to sham. However, spinal EAAC1 was significantly (p = 0.0003) reduced compared to sham. Further, spinal mGluR5 expression was significantly positively correlated to capsule strain (p < 0.02) and mechanical allodynia (p < 0.02). Spinal EAAC1 expression was significantly negatively related to one of the strain metrics (p < 0.003) and mechanical allodynia at day 7 (p = 0.03). These results suggest that the spinal glutamatergic system may potentiate the persistent behavioral hypersensitivity that is produced following dynamic whiplash-like joint loading; chronic whiplash pain may be alleviated by blocking mGluR5 expression and/or enhancing glutamate transport through the neuronal transporter EAAC1.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6392, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000818:Animals; D018771:Arthralgia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002574:Cervical Vertebrae / Q000293:injuries / Q000294:innervation / Q000503:physiopathology*; D004195:Disease Models, Animal; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019547:Neck Pain / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology; D009619:Nociceptors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology; D014911:Whiplash Injuries / Q000378:metabolism / Q000503:physiopathology*; D021801:Zygapophyseal Joint / Q000293:injuries / Q000294:innervation / Q000503:physiopathology*
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C493398:Slc1a1 protein, rat; D018698:Glutamic Acid