title: Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration.
abstract: METHODS
  In vivo study defining expression of the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical intervertebral discs after painful whole-body vibration (WBV).
  
  
  OBJECTIVE
  The goal of this study is to determine if BDNF and NGF are expressed in cervical discs after painful WBV in a rat model.
  
  
  BACKGROUND
  WBV is a possible source of neck pain and has been implicated as increasing the risk for disc disorders. Typically, aneural regions of painful human lumbar discs exhibit hyperinnervation, suggesting nerve ingrowth as potentially contributing to disc degeneration and pain. BDNF and NGF are upregulated in painfully degenerate lumbar discs and hypothesized to contribute to this pathology.
  
  
  METHODS
  Male Holtzman rats underwent 7 days of repeated WBV (15 Hz, 30 min/d) or sham exposures, followed by 7 days of rest. Cervical discs were collected for analysis of BDNF and NGF expression through RT-qPCR and Western blot analysis. Immunohistochemistry also evaluated their regional expression in the disc.
  
  
  RESULTS
  Vibration significantly increases BDNF messenger ribonucleic acid (mRNA) levels (P=0.036), as well as total-NGF mRNA (P=0.035). Protein expression of both BDNF (P=0.006) and the 75-kDa NGF (P=0.045) increase by nearly 4- and 10-fold, respectively. Both BDNF mRNA (R=0.396; P=0.012) and protein (R=0.280; P=0.035) levels are significantly correlated with the degree of behavioral sensitivity (i.e., pain) at day 14. Total-NGF mRNA is also significantly correlated with the extent of behavioral sensitivity (R=0.276; P=0.044). Both neurotrophins are most increased in the inner annulus fibrosus and nucleus pulposus.
  
  
  CONCLUSIONS
  The increases in BDNF and NGF in the cervical discs after painful vibration are observed in typically aneural regions of the disc, consistent with reports of its hyperinnervation. Yet, the induction of nerve ingrowth into the disc was not explicitly investigated. Neurotrophin expression also correlates with behavioral sensitivity, suggesting a role for both neurotrophins in the development of disc pain.
  
  
  METHODS
  N/A.
authors.affiliation: Departments of *Bioengineering and †Neurosurgery, University of Pennsylvania, Philadelphia, PA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Kartha
authors.forename: Martha E
authors.initials: ME
authors.lastname: Zeeman
authors.forename: Hassam A
authors.initials: HA
authors.lastname: Baig
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Guarino
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D002574:Cervical Vertebrae; D012090:Cumulative Trauma Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism*; D008297:Male; D019547:Neck Pain / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014732:Vibration / Q000009:adverse effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020932:Nerve Growth Factor