Neuropathic pain-like alterations in muscle nociceptor function associated with vibration-induced muscle pain

Abstract

We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ~44 Hz during a 1 minute suprathreshold stimulus) much greater than has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves, and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome.

IB4(+) nociceptors mediate persistent muscle pain induced by GDNF

“…The in vivo single fiber electrophysiology technique for studying muscle afferents has been described in detail previously (Chen et al 2010). In brief, rats were anesthetized with pentobarbital sodium (initially 50 mg/kg ip with additional doses given throughout the experiment to maintain areflexia), their trachea was cannulated, and their heart rate was monitored.…”

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

“…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.…”

Role of Kv4.3 in Vibration-Induced Muscle Pain in the Rat

“…The electrophysiological changes observed in this model suggest that they are caused by a traumatic injury of the tibial nerve; many nociceptors innervating the vibration-exposed gastrocnemius muscle become hyperexcitable, displaying enhanced responses to noxious mechanical stimuli and a reduced mechanical threshold 15 . Moreover, nociceptors exposed to vibration-injury are primed and therefore demonstrate enhanced and prolonged hyperalgesia in response to a subsequent pro-inflammatory mediator, even months after the initial injury 2144 .…”

“…To induce muscle hyperalgesia, the hind limbs of rats were subjected to mechanical vibration with a laboratory vortex mixer (Digital Vortex Genie II; Thermo Fisher Scientific, Waltham, MA), as previously described 31521 . These rats were anesthetized with 3% isoflurane in oxygen before one hind leg was affixed to the platform of the vortex mixer with Micropore® surgical tape (Thermo Fisher Scientific) so that the knee and ankle joint were both at 90°, without rotational torque on the leg.…”

“…Our laboratory developed a rodent model for hand-arm vibration syndrome in which the hind limb of an anesthetized rat is vibrated at frequencies comparable to those produced by hand-held power tools 1521 . The electrophysiological changes observed in this model suggest that they are caused by a traumatic injury of the tibial nerve; many nociceptors innervating the vibration-exposed gastrocnemius muscle become hyperexcitable, displaying enhanced responses to noxious mechanical stimuli and a reduced mechanical threshold 15 .…”