Mechanisms Mediating Vibration-Induced Chronic Musculoskeletal Pain Analyzed in the Rat

Abstract

While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a pro-inflammatory cytokine or re-exposure to vibration. Exposure of a hind limb to vibration produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for ~2 weeks. When nociceptive thresholds had returned to baseline, exposure to a pro-inflammatory cytokine or re-exposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration-and cytokine-hyperalgesia induced by vibration was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cε, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-α (TNFα) receptor. Finally, in TNFα-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged.Perspective-These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFα and the second messenger PKCε as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome.

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…Interestingly, this signaling pathway was restricted to IB 4 -positive nonpeptidergic DRG neurons. Recently, a similar PKC-dependent priming has been demonstrated in the skeletal muscle of rats induced by either carrageenan or mechanical vibration (152,153).…”

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

“…Rodent models are useful to investigate the mechanisms of injury and pain [23,39,78,85,86]. Vibration of isolated limbs or the tail induces local myelin damage, endothelial cell death, growth factor upregulation, and increased vulnerability to reinjury [3,21,26,49,53].…”

“…Because the greatest injury risk exists at resonance [36], studies have defined the resonant frequency of many species, including humans (approximately 4 Hz) [11,63], Rhesus monkey (5-14 Hz) [72], and rabbit (4.5 Hz) [80]. Although several rat models have examined pain induction and maintenance after either vibration of isolated limbs or WBV [3,4,11,19,26,43], the vibration response, and its relevance to injury, in the rat is unknown.…”

“…The protein kinase C (PKC) pathway and in particular, the PKCe isoform regulate peripheral nociceptor function [41,77] and contribute to prolonged pain [1,25,26,28,43]. PKCe is responsible for heat and pain sensitivity in peripheral nociceptors [16,93] and, through PKC pathway signaling, also modulates spinal calcitonin gene-related peptide (CGRP) activity [69,74].…”

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“…Inflammation is considered as a primary nonspecific immune response in which the body reacts to any kind of infection, irritation or injury 4 . The primary cause of inflammation is a pure mechanical stress, including blunt trauma 5,6 , foreign bodies 7,8 , vibrations 9,10 and chronic pressure of low intensity 11,12 . Inflammatory responses take place in different phases each mediated by different mechanisms.…”