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

Abstract

Structured Abstract Study Design In vivo study defining expression of the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical intervertebral discs following painful whole body vibration. Objective The goal of this study is to determine if BDNF and NGF are expressed in cervical discs after painful whole body vibration in a rat model. Summary of Background Data Whole body vibration is a possible source of neck pain and has been implicated as increasing the risk for disc disorders. Typically anneural regions of painful human lumbar discs exhibit hyper-innervation, suggesting nerve in-growth 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 seven days of repeated whole body vibration (15Hz, 30 minutes/day) or sham exposures, followed by seven 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 mRNA levels (p=0.036), as well as total NGF mRNA (p=0.035). Protein expression of both BDNF (p=0.006) and the 75kDa 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 (p=0.044, R2=0.276). 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 anneural regions of the disc, consistent with reports of its hyper-innervation. Yet, the induction of nerve in-growth 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.

Whole-body Vibration at Thoracic Resonance Induces Sustained Pain and Widespread Cervical Neuroinflammation in the Rat

“…More recently, it has been found that WBV induces widespread pain and aberrant nerve fiber growth [11,40,71], but the resonance condition has not been investigated. Accordingly, we defined the resonance frequency of the rat spine, because that species is used to study pain and evaluate potential therapeutics [23,39,60,78,85,86].…”

“…Accordingly, we defined the resonance frequency of the rat spine, because that species is used to study pain and evaluate potential therapeutics [23,39,60,78,85,86]. We hypothesized that vibration at resonance produces more robust pain than nonresonant WBV [11,40] and that the neuroimmune cellular and molecular pathways are more extensively activated for that WBV exposure.…”

“…Upregulation of neurotrophins in the intervertebral discs is also evident for the case with sustained pain [40]. Although that collection of work supports the notion that WBV causes pain, it does not address whether sustained pain is possible after a single WBV exposure and the relative role of the resonance frequency on pain and injury risk.…”

“…Rats (317 ± 20 g) were vibrated at resonance (8 Hz, n = 10) and also at a frequency (15 Hz, n = 10) that has been previously characterized [11,40]. Vibration was imposed under inhalation anesthesia (4% induction, 2% maintenance) in the two separate groups.…”

“…To control for anesthetic effects, a sham group (n = 10) underwent the same exposure paradigm but was not vibrated. WBV was imposed as described for the resonance study but with the accelerometer strapped to the rat [11,40]. Vibration was applied for 30 minutes on Days 0 and 7 for all WBV rats used in this study [11].…”