Riveting hammer vibration damages mechanosensory nerve endings.

Hand-arm vibration syndrome (HAVS) is an irreversible neurodegenerative, vasospastic, and musculoskeletal occupational disease of workers who use powered hand tools. The etiology is poorly understood. Neurological symptoms include numbness, tingling, and pain. This study examines impact hammer vibration-induced injury and recoverability of hair mechanosensory innervation. Rat tails were vibrated 12 min/d for 5 weeks followed by 5 week recovery with synchronous non-vibrated controls. Nerve fibers were PGP9.5 immunostained. Lanceolate complex innervation was compared quantitatively in vibrated vs sham. Vibration peak acceleration magnitudes were characterized by frequency power spectral analysis. Average magnitude (2515 m/s2 , root mean squared) in kHz frequencies was 109 times that (23 m/s2 ) in low Hz. Percentage of hairs innervated by lanceolate complexes was 69.1% in 5-week sham and 53.4% in 5-week vibration generating a denervation difference of 15.7% higher in vibration. Hair innervation was 76.9% in 5-weeks recovery sham and 62.0% in 5-week recovery vibration producing a denervation difference 14.9% higher in recovery vibration. Lanceolate number per complex (18.4 ± 0.2) after vibration remained near sham (19.3 ± 0.3), but 44.9% of lanceolate complexes were abnormal in 5 weeks vibrated compared to 18.8% in sham. The largest vibration energies are peak kHz accelerations (approximately 100 000 m/s2 ) from shock waves. The existing ISO 5349-1 standard excludes kHz vibrations, seriously underestimating vibration injury risk. The present study validates the rat tail, impact hammer vibration as a model for investigating irreversible nerve damage. Persistence of higher denervation difference after 5-week recovery suggests repeated vibration injury destroys the capability of lanceolate nerve endings to regenerate.

Use Of Ankle Immobilization In Evaluating Treatments To Promote Longitudinal Muscle Growth In Mice.

INTRODUCTION: Difficulty in modeling congenital contractures (deformities of muscle-tendon unit development that include shortened muscles and lengthened tendons) has limited research of new treatments. METHODS: Early immobilization of the ankle in prepuberal mice was used to produce deformities similar to congenital contractures. Stretch treatment, electrostimulation, and local intramuscular injection of a follistatin analog (FST-288) were assessed as therapeutic interventions for these deformities. RESULTS: Ankle immobilization at full plantarflexion and 90 ° created tendon lengthening and muscle shortening in the tibialis anterior and soleus. Stretch treatment produced minimal evidence for longitudinal muscle growth and electrostimulation provided no additional benefit. Stretch treatment with FST-288 produced greater longitudinal muscle growth and less tendon lengthening, constituting the best treatment response. DISCUSSION: Ankle immobilization recapitulates key morphologic features of congenital contracture, and these features can be mitigated by a combination of stretch and pharmacological approaches that may be useful in patients. Muscle Nerve 58: 718-725, 2018.

Long-term daily vibration exposure alters current perception threshold (CPT) sensitivity and myelinated axons in a rat-tail model of vibration-induced injury.

Repeated exposure to hand-transmitted vibration through the use of powered hand tools may result in pain and progressive reductions in tactile sensitivity. The goal of the present study was to use an established animal model of vibration-induced injury to characterize changes in sensory nerve function and cellular mechanisms associated with these alterations. Sensory nerve function was assessed weekly using the current perception threshold test and tail-flick analgesia test in male Sprague-Dawley rats exposed to 28 d of tail vibration. After 28 d of exposure, Aß fiber sensitivity was reduced. This reduction in sensitivity was partly attributed to structural disruption of myelin. In addition, the decrease in sensitivity was also associated with a reduction in myelin basic protein and 2',3'- cyclic nucleotide phosphodiasterase (CNPase) staining in tail nerves, and an increase in circulating calcitonin gene-related peptide (CGRP) concentrations. Changes in Aß fiber sensitivity and CGRP concentrations may serve as early markers of vibration-induced injury in peripheral nerves. It is conceivable that these markers may be utilized to monitor sensorineural alterations in workers exposed to vibration to potentially prevent additional injury.

Stretch-activated signaling is modulated by stretch magnitude and contraction.

INTRODUCTION: Stretch therapy is commonly utilized to prevent shortening maladaptation of skeletal muscle. Stretch in combination with isometric contraction prevents shortening, but the signaling mechanisms are not understood. METHODS: Using a soleus tenotomy + stretch rat model, the phosphorylation-activation of mechanosensitive kinases (Akt, p70(S6K), p38 MAPK, and ERK1/2) were measured for various stretch magnitudes, set relative to optimal soleus length (Lo). RESULTS: The kinases were not activated by passive stretch until it exceeded the normal physiological range. Stretch + isometric contraction resulted in relatively strong phosphorylation, even at short lengths. CONCLUSIONS: Whereas passive stretch results in kinase phosphorylation only during extreme lengthening, isometric contraction generated pronounced phosphorylation of kinases at Lo and Lo + 25%, indicating stimulation of pathways that lead to the preservation or increase of muscle length. Understanding the effects of passive and active stretch with respect to Lo and contraction is essential for predicting therapeutic outcomes and influencing optimal muscle length.

Frequency-dependent effects of vibration on physiological systems: experiments with animals and other human surrogates.

Occupational exposure to vibration through the use of power- and pneumatic hand-tools results in cold-induced vasospasms, finger blanching, and alterations in sensorineural function. Collectively, these symptoms are referred to as hand-arm vibration syndrome (HAVS). Currently the International Standards Organization (ISO) standard ISO 5349-1 contains a frequency-weighting curve to help workers and employers predict the risk of developing HAVS with exposure to vibration of different frequencies. However, recent epidemiological and experimental evidence suggests that this curve under-represents the risk of injuries to the hands and fingers induced by exposure to vibration at higher frequencies (>100 Hz). To improve the curve, better exposure-response data need to be collected. The goal of this review is to summarize the results of animal and computational modeling studies that have examined the frequency-dependent effects of vibration, and discuss where additional research would be beneficial to fill these research gaps.

Preserving sarcomere number after tenotomy requires stretch and contraction.

INTRODUCTION: Passive stretch therapy is utilized to improve the range of motion of chronically shortened muscles. However, human studies show conflicting results as whether passive stretch is clinically effective. METHODS: The soleus muscles of adult rats were tenotomized to induce muscle shortening adaptation. Muscles included were non-treated normal, subjected to daily static stretch, or lengthened and isometrically contracted for 20 min/day. Muscle fiber structure was analyzed histochemically. Sarcomeres per millimeter length were counted to assess the effect of treatment. RESULTS: Passive stretch significantly reduced central core lesion formation, but sarcomere loss was not prevented. The addition of isometric contraction during static stretch significantly (P < 0.001) reduced sarcomere loss. CONCLUSIONS: Passive stretch alone does not prevent shortening adaptation. Contraction is required in combination with stretch to preserve the number of sarcomeres in series. The combination of stretch and contraction is necessary to maintain proper muscle fiber length.

The effects of active and passive stretching on muscle length.

Active stretch is necessary for regulating muscle fiber length (ie, the number of series sarcomeres). Elevated cytoplasmic calcium is the proposed component of contractile activity required to activate signaling pathways for sarcomere number regulation. Passive stretch reduces muscle tissue stiffness, most likely by signaling connective tissue remodeling via fibroblasts. Passive stretch may induce sarcomere addition if the muscle fibers are lengthened sufficiently to raise cytoplasmic calcium through stretch-activated calcium channels. The magnitude of stretch in vivo is limited by the physiologic range of movement and stretch pain tolerance. The greatest effect of stretching muscle fibers is expected when the lengthening exceeds the optimum fiber length (Lo).

Evaluation of anti-vibration effectiveness of glove materials using an animal model.

Gloves with anti-vibration features are increasingly used to reduce impact vibrations or shocks transmitted to the hands of power tool operators. Selection and evaluation of the glove materials are important steps in the designs of such gloves. In the current study, we proposed an approach to objectively evaluate the effectiveness of the glove materials using a rat-tail impact model. As a critical part of a systematic investigation, we examined the vibration reduction characteristics of typical resilient glove materials (air bladders and viscoelastic gels) and the impact vibrations transmitted to the rat tail. A special test platform that mimics impact tool vibrations was constructed and used in the experiment. A scanning laser vibrometer was used to measure the vibration at points across the platform surface under several different test conditions. The peak acceleration was found to be greatly attenuated by the glove materials, especially by using strips from a gel-filled glove. The rat tail was found to effectively absorb the high-frequency vibration. However, the glove materials and the rat tail did not reduce the frequency-weighted acceleration. The implications of the experimental results are discussed.

Electrophysiological dysfunction in the peripheral nervous system following spinal cord injury.

OBJECTIVE: To evaluate peripheral nervous system function after chronic spinal cord injury (SCI). DESIGN: Case series. SETTING: Academic medical center. PARTICIPANTS: Sixteen subjects (13 men, 3 women) with complete thoracic or cervical level SCI of 3-32 years' duration since injury. METHODS: Clinical electrophysiology of the lower extremities. MAIN OUTCOME MEASUREMENTS: Compound motor action potentials (CMAP), sensory nerve action potentials, repetitive nerve stimulation, concentric needle electromyography (EMG), stimulated single-fiber EMG. RESULTS: Subject ages ranged from 20 to 71 years with a mean (SD) of 42 ± 15 years. The average time since injury was 11 ± 8 years (range, 3-32 years). Sural sensory nerve action potentials were elicited in only 4 of 16 subjects (25%), and peroneal CMAPs were elicited in 7 of 16 subjects (44%). All of the subjects had spontaneous activity (fibrillation and/or sharp potentials) in at least 1 of 4 tested muscles. Eighty-one percent of subjects demonstrated spontaneous activity in 3 of the 4 tested muscles. Peroneal motor repetitive nerve stimulation was within normal limits for 7 subjects but could not be performed in the other 9 subjects because of the absence of CMAPs. Stimulated single-fiber EMG was elicited in the tibialis anterior, extensor digitorum brevis, vastus lateralis, or vastus medialis muscles of 8 of 16 subjects. CONCLUSIONS: The high prevalence of spontaneous activity demonstrates that denervation of the skeletal muscles served by motor neurons below the level of the lesion occurs in individuals with chronic complete SCI. The electrophysiological testing revealed the striking absence of sensory and motor nerve conduction and aberrant neuromuscular junction transmission. It is important to understand the mechanisms that underlie the profound reduction of the functional integrity of the peripheral nervous system to maximize the restoration of movement, particularly should descending neural control be reestablished by a future therapy.

The preventive effects of apolipoprotein mimetic D-4F from vibration injury-experiment in rats.

Hand-arm vibration syndrome (HAVS) is a debilitating sequela of neurological and vascular injuries caused by prolonged occupational exposure to hand-transmitted vibration. Our previous study demonstrated that short-term exposure to vibration can induce vasoconstriction and endothelial cell damage in the ventral artery of the rat's tail. The present study investigated whether pretreatment with D-4F, an apolipoprotein A-1 mimetic with known anti-oxidant and vasodilatory properties, prevents vibration-induced vasoconstriction, endothelial cell injury, and protein nitration. Rats were injected intraperitoneally with 3 mg/kg D-4F at 1 h before vibration of the tails for 4 h/day at 60 Hz, 49 m/s(2) r.m.s. acceleration for either 1 or 3 days. Vibration-induced endothelial cell damage was examined by light microscopy and nitrotyrosine immunoreactivity (a marker for free radical production). One and 3-day vibration produced vasoconstriction and increased nitrotyrosine. Preemptive treatment with D-4F prevented these negative changes. These findings suggest that D-4F may be useful in the prevention of HAVS.

Persistent reduction of conduction velocity and myelinated axon damage in vibrated rat tail nerves.

Prolonged hand-transmitted vibration exposure in the workplace has been recognized for almost a century to cause neurodegenerative and vasospastic disease. Persistence of the diseased state for years after cessation of tool use is of grave concern. To understand persistence of vibration injury, the present study examined recovery of nerve conduction velocity and structural damage of myelinated axons in a rat tail vibration model. Both 7 and 14 days of vibration (4 h/day) decreased conduction velocity. The decrease correlated directly with the increased percentage of disrupted myelinated axons. The total number of myelinated axons was unchanged. During 2 months of recovery, conduction velocity returned to control level after 7-day vibration but remained decreased after 14-day vibration. The rat tail model provides insight into understanding the persistence of neural deficits in hand-arm vibration syndrome.

Exercise in space: human skeletal muscle after 6 months aboard the International Space Station.

The aim of this investigation was to document the exercise program used by crewmembers (n = 9; 45 +/- 2 yr) while aboard the International Space Station (ISS) for 6 mo and examine its effectiveness for preserving calf muscle characteristics. Before and after spaceflight, we assessed calf muscle volume (MRI), static and dynamic calf muscle performance, and muscle fiber types (gastrocnemius and soleus). While on the ISS, crewmembers had access to a running treadmill, cycle ergometer, and resistance exercise device. The exercise regimen varied among the crewmembers with aerobic exercise performed approximately 5 h/wk at a moderate intensity and resistance exercise performed 3-6 days/wk incorporating multiple lower leg exercises. Calf muscle volume decreased (P < 0.05) 13 +/- 2% with greater (P < 0.05) atrophy of the soleus (-15 +/- 2%) compared with the gastrocnemius (-10 +/- 2%). Peak power was 32% lower (P < 0.05) after spaceflight. Force-velocity characteristics were reduced (P < 0.05) -20 to -29% across the velocity spectrum. There was a 12-17% shift in myosin heavy chain (MHC) phenotype of the gastrocnemius and soleus with a decrease (P < 0.05) in MHC I fibers and a redistribution among the faster phenotypes. These data show a reduction in calf muscle mass and performance along with a slow-to-fast fiber type transition in the gastrocnemius and soleus muscles, which are all qualities associated with unloading in humans. Future long-duration space missions should modify the current ISS exercise prescription and/or hardware to better preserve human skeletal muscle mass and function, thereby reducing the risk imposed to crewmembers.

Stretch reduces central core lesions and calcium build-up in tenotomized soleus.

The incidence of skeletal muscle tendon rupture is increasing. The unloaded, shortened muscle undergoes rapid degeneration. Rehabilitation takes 10-12 weeks and includes stretch therapy. Outcomes may be improved by understanding the pathophysiological changes and stretch mechanisms. We investigated the effects of passive stretch on preventing central core lesions in a rat tenotomy model of simulated Achilles tendon rupture. Adult male rats were tenotomized bilaterally. At 7 days, 39% of the soleus fibers possessed central core lesions. Whole muscle calcium concentration progressively increased and plateaued by 4 days. Dantrolene, a calcium release blocker, injected daily for 7 days, reduced central core lesion formation and calcium build-up. Passive stretch, 20 min/day, inhibited central core lesion formation. Calcium increased at 4 days in mitochondria, and stretch prevented this increase. These findings indicate that stretch therapy reduces central core lesion occurrence by preventing calcium elevation in hypershortened muscles.

Serological tests for diagnosis and staging of hand-arm vibration syndrome (HAVS).

The current gold standard for the diagnosis and staging of hand-arm vibration syndrome (HAVS) is the Stockholm workshop scale, which is subjective and relies on the patient's recalling ability and honesty. Therefore, great potentials exist for diagnostic and staging errors. The purpose of this study is to determine if objective serum tests, such as levels of soluble thrombomodulin (sTM) and soluble intercellular adhesion molecule-1 (sICAM-1), may be used in the diagnosis and staging of HAVS. Twenty two nonsmokers were divided into a control group (n = 11) and a vibration group (n = 11). The control group included subjects without history of frequent vibrating tool use. The vibration group included construction workers with average vibrating tool use of 12.2 years. All were classified according to the Stockholm workshop scale (SN, sensorineural symptoms; V, vascular symptoms. SN0, no numbness; SN1, intermittent numbness; SN2, reduced sensory perception; SN3, reduced tactile discrimination; V0, no vasospasmic attacks; V1, intermittent vasospasm involving distal phalanges; V2, intermittent vasospasm extending to middle phalanges; V3, intermittent vasospasm extending to proximal phalanges; V4, skin atrophy/necrosis). All control subjects were SN0 V0. Seven out of 11 vibration subjects were SN1 V1, and 4 out of 11 were SN1 V2. A 10-cm(3) sample of venous blood was collected from each subject. The sTM and sICAM-1 levels were determined by enzyme-linked immunosorbent assay. The mean plasma sTM levels were as follows: control group = 2.93 +/- 0.47 ng/ml, and vibration group = 3.61 +/- 0.24 ng/ml. The mean plasma sICAM-1 levels were as follows: control group = 218.8 +/- 54.1 ng/ml, and vibration group = 300.3 +/- 53.2 ng/ml. The sTM and sICAM-1 differences between control and vibration groups were statistically significant (p < 0.0002 and p < 0.001, respectively). When reference ranges provided by Hemostasis Reference Lab were used as cut-off values, all sTM and sICAM-1 levels were within range, except three vibration individuals (27%) who had sICAM-1 levels greater than the reference range. This was not statistically significant (p = 0.08). When subjects were compared based on the Stockholm workshop scale, mean plasma sTM levels were SN0 V0 group = 2.93 +/- 0.47 ng/ml, SN1 V1 group = 3.59 +/- 0.25 ng/ml, and SN1 V2 group = 3.65 +/- 0.27 ng/ml, and mean plasma sICAM-1 levels were SN0 V0 = 219 +/- 54.1 ng/ml, SN1 V1 = 275 +/- 33.5 ng/ml, and SN1 V2 = 345 +/- 54.6 ng/ml. The difference in sTM level among the three groups was statistically significant (p < 0.001). The difference in sICAM-1 level among the three groups was also statistically significant (p < 0.002). The sTM and sICAM-1 levels are statistically higher in subjects with HAVS, with levels proportional to the disease severity. However, large population studies are needed to determine the "real-life" standard reference ranges for sTM and sICAM-1.

Vibration causes acute vascular injury in a two-step process: vasoconstriction and vacuole disruption.

Hand-arm vibration syndrome is a vasospastic and neurodegenerative occupational disease. In the current study, the mechanism of vibration-induced vascular smooth muscle cell (SMC) injury was examined in a rat-tail vibration model. Tails of male Sprague Dawley rats were vibrated continuously for 4 hr at 60 Hz, 49 m/s(2) with or without general anesthesia. Ventral tail arteries were aldehyde fixed and embedded in epoxy resin to enable morphological analysis. Vibration without anesthesia caused vasoconstriction and vacuoles in the SMC. Anesthetizing rats during vibration prevented vasoconstriction and vacuole formation. Exposing tail arteries in situ to 1 mM norepinephrine (NE) for 15 min induced the greatest vasoconstriction and vacuolation. NE induced vacuoles were twice as large as those formed during vibration. When vibrated 4 hr under anesthesia after pretreatment with NE for 15 min, the SMC lacked vacuoles and exhibited a longitudinal banding pattern of dark and light staining. The extracellular matrix was filled with particulates, which were confirmed by electron microscopy to be cellular debris. The present findings demonstrate that vibration-induced vasoconstriction (SMC contraction) requires functioning central nervous system reflexes, and the physical stress of vibration damages the contracted SMC by dislodging and fragmenting SMC vacuoles.

Comparison of continuous and intermittent vibration effects on rat-tail artery and nerve.

Hand-transmitted vibration from powered-tools can cause peripheral vasospasm and neuropathy. A rat-tail model was used to investigate whether the pattern of vibration influenced the type and severity of tissue damage. The tails of awake rats were vibrated continuously or intermittently for a total of 4 hours at 60 HZ, 49 m/s(2). Nerves and arteries were harvested immediately or 24 hours after treatment. Tails subjected to intermittent vibration showed transiently increased sensitivity to thermal stimuli. Intermittent vibration caused the most nerve injury immediately and 24 hours after vibration. Continuous vibration invoked a persistent reduction in vascular lumen size. Compared to epinephrine-induced transient vacuolation in vascular smooth muscle cells, both continuous and intermittent vibration caused greater persistence of vacuoles, indicating a vibration-induced pathological process. All vibration groups exhibited elevated nitrotyrosine immunoreactivity indicative of free-radical damage. Pattern of vibration exposure may exert a major influence on the type of vibration injury.

Effects of temperature on vibration-induced damage in nerves and arteries.

Vasospastic episodes in hand-arm vibration syndrome are more prevalent among power-tool workers in cold climates. To test whether cold enhances vibration-induced damage in arteries and nerves, tails of Sprague-Dawley rats were vibrated at room temperature (RT) or with tail cooling (<15 degrees C). Cold vibration resulted in a colder tail than either treatment alone. Vibration at both temperatures reduced arterial lumen size. RT vibration generated more vacuoles in arteries than cold vibration. Vibration and cold induced nitration of tyrosine residues in arteries, suggesting free-radical production. Vibration and cold generated similar percentages of myelinated axons with disrupted myelin. Cold with and without vibration caused intraneural edema and dilation of arterioles and venules with blood stasis, whereas vibration alone did not. The similarities, differences, and interactive effects of cold and vibration on nerve and artery damage indicate that temperature is involved mechanistically in the pathophysiology of hand-arm vibration syndrome.

Nifedipine pretreatment reduces vibration-induced vascular damage.

A rat-tail vibration model of hand-arm vibration was employed to test whether preemptive administration of nifedipine (5 mg/kg) to block vasoconstriction prevents vibration-induced arterial damage. The tails of vibrated and nifedipine-pretreated vibrated Sprague-Dawley rats were exposed continuously to 4 h of 60-HZ vibration at 49 m/s(2) rms. In nonvibrated anesthetized rats, the ventral tail arteries were bathed for 15 min in situ in 1 mM epinephrine or 1 mM norepinephrine to induce structural changes indicative of intense vasoconstriction. Arteries were processed for light and electron microscopy 45 min after treatment. Compared to sham control, 4-h vibration significantly (P < 0.01) reduced lumen size, generated endothelial disruption (7.0 +/- 2.6%), elevated nuclear factor of activated T cells c3 (NFATc3) expression in endothelial and smooth muscle cells, and increased smooth muscle cell vacuolization. The findings demonstrate that blockage of vibration-induced vasoconstriction with nifedipine prevents acute vascular damage. Smooth muscle and endothelial cells structurally altered by vasoconstriction are rendered susceptible to damage by vibration.

Vibration-induced disruption of retrograde axoplasmic transport in peripheral nerve.

Hand-arm vibration syndrome (HAVS) results from excessive exposure to hand-transmitted vibration. Whether the peripheral nerve damage characteristic of HAVS is a direct result of vibration or is secondary to vascular insufficiency remains unclear. The purpose of this study was to explore the effect of vibration exposure on axoplasmic transport in peripheral nerves and soleus motor neurons. Sciatic nerves and motor neurons from rats following two 5-h periods of vibration exposure demonstrated disruption in retrograde transport compared to normal. After 10 days of vibration (5 h/day), axoplasmic transport failed to recover within 24-48 h in most rats. This study demonstrates that disrupted axoplasmic transport is an early consequence of short-term vibration exposure. The effects of vibration on axoplasmic transport also appear to be cumulative. This study provides a new biological way to evaluate measures to prevent early vibration injury.

Evidence for frequency-dependent arterial damage in vibrated rat tails.

The effects of single 4-hr bouts of continuous 30, 60, 120, and 800 Hz tail vibration (49 m/sec2, root mean squared) were compared to assess frequency-amplitude-related structural damage of the ventral caudal artery. Amplitudes were 3.9, 0.98, 0.24, and 0.0055 mm, respectively. Vibrated, sham-vibrated, and normal arteries were processed for light and electron microscopy. The Curry rat tail model of hand-arm vibration (Curry et al. Muscle Nerve 2002;25:527-534) proved well-suited for testing multiple frequencies. NFATc3 immunostaining, an early marker of cell damage, increased in smooth muscle and endothelial cells after 30, 60, and 120 Hz but not 800 Hz. Increased vacuolization, which is indicative of smooth muscle contraction, occurred for all frequencies except 800 Hz. Vacuoles increased in both endothelial and smooth muscle cells after 60 and 120 Hz. Only 30 Hz showed pronounced smooth muscle cell vacuolization along the internal and external elastic membranes, suggesting stretch-mediated contraction from the large amplitude shear stress. Discontinuities in toluidine blue staining of the internal elastic membrane (IEM) increased for all frequencies, indicating vibration-induced structural weakening of this structure. Patches of missing IEM and overlying endothelium occurred in approximately 5% of arteries after 60, 120, and 800 Hz. The pattern of damage after 800 Hz suggests that the IEM is disrupted because it resonates at this frequency. Vibration acceleration stress and smooth muscle contraction appear to be the major contributors to arterial damage. The pattern of vibration-induced arterial damage of smooth muscle and endothelial cells is frequency-amplitude-dependent.