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Upregulation of BDNF and NGF in Cervical Intervertebral Discs Exposed to Painful Whole-Body Vibration

Kartha, Sonia BS*; Zeeman, Martha E. MS*; Baig, Hassam A. MS*; Guarino, Benjamin B. BS*; Winkelstein, Beth A. PhD*,†

doi: 10.1097/BRS.0000000000000457
Basic Science

Study Design. 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.

Summary of Background Data. 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 (R2 = 0.396; P = 0.012) and protein (R2 = 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 (R2 = 0.276; P = 0.044). Both neurotrophins are most increased in the inner annulus fibrosus and nucleus pulposus.

Conclusion. 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.

Level of Evidence: N/A

Expression of the neurotrophins, brain-derived neurotrophic factor and nerve growth factor, increases in the cervical intervertebral discs after painful whole-body vibration in the rat. Upregulation of both is evident in the typically aneural inner annulus fibrosus and nucleus pulposus, suggesting that whole-body vibration may induce similar mechanisms as in painful degenerate discs.

Departments of *Bioengineering and

Neurosurgery, University of Pennsylvania, Philadelphia, PA.

Address correspondence and reprint requests to Beth A. Winkelstein, PhD, Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 S. 33rd St, Philadelphia, PA 19104-6321; E-mail: winkelst@seas.upenn.edu

Acknowledgment date: March 21, 2014. Revision date: May 21, 2014. Acceptance date: May 27, 2014.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Department of Defense (W81XWH-10-2-0140) and the National Institutes of Health (NIAMS) (AR064157) grant funds were received to support this work.

Relevant financial activities outside the submitted work: grants.

© 2014 by Lippincott Williams & Wilkins