Background Whole-body vibration (WBV) is associated with back and neck pain in military personnel and civilians. However, the role of vibration frequency and the physiological mechanisms involved in pain symptoms are unknown. Questions/purposes This study asked the following questions: (1) What is the resonance frequency of the rat spine for WBV along the spinal axis, and how does frequency of WBV alter the extent of spinal compression/ extension? (2) Does a single WBV exposure at resonance induce pain that is sustained? (3) Does WBV at resonance alter the protein kinase C epsilon (PKCe) response in the dorsal root ganglia (DRG)? (4) Does WBV at resonance alter expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn? (5) Does WBV at resonance alter the spinal neuroimmune responses that regulate pain? Methods Resonance of the rat (410 ± 34 g, n = 9) was measured by imposing WBV at frequencies from 3 to 15 Hz. Separate groups (317 ± 20 g, n = 10/treatment) underwent WBV at resonance (8 Hz) or at a nonresonant frequency (15 Hz). Behavioral sensitivity was assessed throughout to measure pain, and PKCe in the DRG was quantified as well as spinal CGRP, glial activation, and cytokine levels at Day 14. Results Accelerometer-based thoracic transmissibility peaks at 8 Hz (1.86 ± 0.19) and 9 Hz (1.95 ± 0.19, mean difference [MD] 0.290 ± 0.266, p \ 0.03), whereas the video-based thoracic transmissibility peaks at 8 Hz (1.90 ± 0.27), 9 Hz (2.07 ± 0.20), and 10 Hz (1.80 ± 0.25, MD 0.359 ± 0.284, p \ 0.01). WBV at 8 Hz produces more cervical extension (0.745 ± 0.582 mm, MD 0.242 ± 0.214, p \ 0.03) and compression (0.870 ± 0.676 mm, MD 0.326 ± 0.261, p \ 0.02) than 15 Hz (extension, 0.503 ± 0.279 mm; compression, 0.544 ± 0.400 mm). Pain is longer lasting (through Day 14) and more robust (p \ 0.01) after WBV at the resonant frequency (8 Hz) compared with 15 Hz WBV. PKCe in the nociceptors of the DRG increases according to the severity of WBV with greatest increases after 8 Hz WBV (p \ 0.03). However, spinal CGRP, cytokines, and glial activation are only evident after painful WBV at resonance. Conclusions WBV at resonance produces long-lasting pain and widespread activation of a host of nociceptive and neuroimmune responses as compared with WBV at a nonresonance condition. Based on this work, future investigations into the temporal and regional neuroimmune response to resonant WBV in both genders would be useful.

Chronic neck pain is one of the most common musculoskeletal disorders in the US. Although biomechanical and clinical studies have implicated the facet joint as a primary source of neck pain, specific cellular mechanisms still remain speculative. The purpose of this study was to investigate whether a mediator (ATF4) of the integrated stress response (ISR) is involved in facet-mediated pain. Holtzman rats underwent C6/C7 facet joint loading that produces either painful (n=16) or nonpainful (n=8) responses. A sham group (n=9) was also included as surgical controls. Behavioral sensitivity was measured and the C6 DRGs were harvested on day 7 to evaluate the total and neuronal ATF4 expression. In separate groups, an intra-articular ketorolac injection was administered either immediately (D0 ketorolac) or 1 day (D1 ketorolac) after painful facet joint loading. Allodynia was measured at days 1 and 7 after injury to assess the effects on behavioral responses. ATF4 and BiP (an indicator of ISR activation) were separately quantified at day 7. Facet joint loading sufficient to elicit behavioral hypersensitivity produced a 3-fold increase in total and neuronal ATF4 expression in the DRG. After ketorolac treatment at the time of injury, ATF4 expression was significantly (p<0.01) reduced despite not producing any attenuation of behavioral responses. Interestingly, ketorolac treatment at day 1 significantly (p<0.001) alleviated behavioral sensitivity at day 7, but did not modify ATF4 expression. BiP expression was unchanged after either intervention time. Results suggest that ATF4-dependent activation of the ISR does not directly contribute to persistent pain, but may sensitize neurons responsible for pain initiation. These behavioral and immunohistochemical findings imply that facet-mediated pain may be sustained through other pathways of the ISR.

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Whole body vibration (WBV) has been linked to neck and back pain, but the biomechanical and physiological mechanisms responsible for its development and maintenance are unknown. A rodent model of WBV was developed in which rats were exposed to different WBV paradigms, either daily for 7 consecutive days (repeated WBV) or two single exposures at Day 0 and 7 (intermittent WBV). Each WBV session lasted for 30 min and was imposed at a frequency of 15 Hz and RMS platform acceleration of 0.56 AE 0.07 g. Changes in the withdrawal response of the forepaw and hind paw were measured, and were used to characterize the onset and maintenance of behavioral sensitivity. Accelerations and displacements of the rat and deformations in the cervical and lumbar spines were measured during WBV to provide mechanical context for the exposures. A decrease in withdrawal threshold was induced at 1 day after the first exposure in both the hind paw and forepaw. Repeated WBV exhibited a sustained reduction in withdrawal threshold in both paws and intermittent WBV induced a sustained response only in the forepaw. Cervical deformations were significantly elevated which may explain the more robust forepaw response. Findings suggest that a WBV exposure leads to behavioral sensitivity. Keywords: whole body vibration; spine; pain; injury Several epidemiological studies have linked exposure to whole body vibration (WBV) with neck and back pain, [1][2][3][4] suggesting that vibration can lead to the onset of both pain syndromes. American male workers operating vibrating vehicles, such as industrial trucks and tractors, have been reported to have a higher prevalence of low back pain and are three-times more susceptible to acute herniated lumbar discs than workers whose occupations do not involve such exposures.3,5 Also, military helicopter aviators report increased pain during deployment compared to their pre-deployment reports of pain, with between 22-37% reporting neck and 39-70% reporting low back pain. 4 Further, the frequency of pain was significantly higher for aviators who experienced substantially increased flight hours during deployment compared to those who did not, 4 suggesting that the amount of exposure to WBV may affect the pain. 4 Despite the strong suggestive evidence of these epidemiological studies that pain can develop from WBV and may be influenced by the nature and frequency of the exposure, there is still little known about how these factors relate to the onset, maintenance, and resolution of pain.A limited number of studies have defined the biomechanical response to vibration and related resonance and vibration frequency to physiological responses known to be involved in pain-related injuries. The resonant frequency of the seated human undergoing vertical vibration has been reported to be 4.5 Hz from a series of studies using accelerometers on the first and third lumbar vertebrae (L1, L3) and the sacrum of volunteers exposed to vertical vibrations, ranging in frequencies from 2 to 15 Hz. 6 A later study using similarl...

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.