Nociceptor Interleukin 33 Receptor/ST2 Signaling in Vibration-Induced Muscle Pain in the Rat.

Occupational exposure to mechanical vibration can produce the hand-arm vibration syndrome (HAVS), whose most disabling symptom is persistent muscle pain. Unfortunately, the pathophysiology of HAVS pain is still poorly understood, precluding the development of mechanism-based therapies. Since interleukin 33 (IL-33) is essential for inflammation and recovery that follows skeletal muscle injury, we explored its role in muscle pain in a model of HAVS, in adult male rats. Concomitant to mechanical hyperalgesia, an increase in IL-33 in the ipsilateral gastrocnemius muscle was observed 24 hours after vibration. A similar hyperalgesia was produced by intramuscular injection of recombinant rat IL-33 (rrIL-33, 10-300 ng). Intrathecal administration of an oligodeoxynucleotide antisense to IL-33R/ST2 mRNA decreased the expression of ST2 in DRG and attenuated both rrIL-33 and vibration-induced mechanical hyperalgesia. Together these data support the suggestion that IL-33 plays a central role in vibration-induced muscle pain by action, at least in part, on skeletal muscle nociceptors. PERSPECTIVE: Our findings provide evidence of the contribution of IL-33, acting on its canonical receptor, in nociceptors, to muscle pain induced by ergonomic vibration. This suggests that targeting IL-33/ST2 signaling may be a useful strategy for the treatment of muscle pain in HAVS.

Interleukin 6 decreases nociceptor expression of the potassium channel KV1.4 in a rat model of hand-arm vibration syndrome.

Chronic muscle pain is a prominent symptom of the hand-arm vibration syndrome (HAVS), an occupational disease induced by exposure to vibrating power tools, but the underlying mechanism remains unknown. We evaluated the hypothesis that vibration induces an interleukin 6 (IL-6)-mediated downregulation of the potassium voltage-gated channel subfamily A member 4 (KV1.4) in nociceptors leading to muscle pain. Adult male rats were submitted to a protocol of mechanical vibration of the right hind limb. Twenty-four hours after vibration, muscle hyperalgesia was observed, concomitant to increased levels of IL-6 in the gastrocnemius muscle and decreased expression of KV1.4 in the dorsal root ganglia. Local injection of neutralizing antibodies against IL-6 attenuated the muscle hyperalgesia induced by vibration, whereas antisense knockdown of this channel in the dorsal root ganglia mimicked the muscle hyperalgesia observed in the model of HAVS. Finally, knockdown of the IL-6 receptor signaling subunit glycoprotein 130 (gp130) attenuated both vibration-induced muscle hyperalgesia and downregulation of KV1.4. These results support the hypothesis that IL-6 plays a central role in the induction of muscle pain in HAVS. This likely occurs through intracellular signaling downstream to the IL-6 receptor subunit gp130, which decreases the expression of KV1.4 in nociceptors.

[Criterial value of oxidative stress parameters in exposure to vibration].

The article covers results of study concerning metabolic processes in workers exposed to vibration. Findings are lipid peroxidation processes activation, depressed anti-oxidant system, changes in intracellular exchange processes, dependence of the studied parameters change on length of service with vibration exposure.

Transcriptional Pathways Altered in Response to Vibration in a Model of Hand-Arm Vibration Syndrome.

OBJECTIVE: The aim of this study was to use an established model of vibration-induced injury to assess frequency-dependent changes in transcript expression in skin, artery, and nerve tissues. METHODS: Transcript expression in tissues from control and vibration-exposed rats (4 h/day for 10 days at 62.5, 125, or 250 Hz; 49 m/s, rms) was measured. Transcripts affected by vibration were used in bioinformatics analyses to identify molecular- and disease-related pathways associated with exposure to vibration. RESULTS: Analyses revealed that cancer-related pathways showed frequency-dependent changes in activation or inhibition. Most notably, the breast-related cancer-1 pathway was affected. Other pathways associated with breast cancer type 1 susceptibility protein related signaling, or associated with cancer and cell cycle/cell survivability were also affected. CONCLUSION: Occupational exposure to vibration may result in DNA damage and alterations in cell signaling pathways that have significant effects on cellular division.

[Forecasting formation and course of vibration disease on basis of genetic metabolic markers study].

Analyzing distribution of genotype polymorphism occurrence of Pro l98Leu gene of GPX1 (glutathion peroxidase) and Ala 16 Val gene of MnSOD (superoxide dismutase), the authors presented major mechanisms and leading pathogenetic factors of vibration disease formation and course in post-contact period. The article covers also results of metabolic processes evaluation in patients with varying resistence to occupational vibration, for forecasting its course after discontinued contact with the factor.

[Neuroimmune endocrine relationships under exposure to local vibration in workers].

The studies prove that local vibration in workers alters parameters of immune, nervous, endocrine systems interconnected and demonstrating pathologic process degree. Findings are that workers with long length of service, having no health disorders, increased CNTF level is associated with high TSH, increased IgG level is connected with ACTH growth. In vibration disease, increase of neurospecific protein S-100ß is associatedwith lower level of T4. Increase of anti-inflammatory IL-4 is accompanied by high level of T3--that can prove disbalance in main regulatory systems (immune, nervous, endocrine).

[THE BALANCE OF EICOSANOIDS WITH VIBRATION DISEASED PATIENTS IN CONJUNCTION WITH HYPERTENSION DISEASE].

The status of vasodilatational and vasoconstrictoral eicosanoids in patients with vibration disease combined with hypertension disease are presented. The increase of the concentration vasodilators observed in patients with vibration disease. The maximum growth vasoconstrictoral eicosanoids observed in groups with comorbidity.

Salivary endothelin and vascular disorders in vibration-exposed workers.

OBJECTIVES: This study investigated the relation between salivary endothelin, vibration exposure, and vascular disorders in a group of forestry workers. METHODS: Altogether 54 forestry workers and 52 controls underwent a medical examination and a cold test with measurement of the percentage of change in finger systolic blood pressure after finger cooling from 30 degrees C to 10 degrees C (FSBP% (10 degrees)). Salivary endothelin concentration (ET(1-21), in fmol/ml) was measured by a commercially available enzyme-linked immunosorbent assay before and after the cold challenge. The anamnestic diagnosis of vibration-induced white finger (VWF), assisted by color charts, was based on the Stockholm Workshop criteria. RESULTS: Six forestry workers (11%) and one control (2%) reported white fingers. Before the cold challenge, the salivary ET(1-21) concentration was significantly greater in the VWF workers than in the controls (P=0.036). The cold response of digital arteries was stronger in the VWF workers than in the controls (P<0.001) and the asymptomatic forestry workers (P=0.008). After the cold test, there was a small, not significant, increase in the salivary ET(1-21) concentration in both the controls and the forestry workers. For the latter, the salivary ET(1-21) concentration was significantly associated with both daily and total operating time with vibrating tools. A significant inverse relation between FSBP% (10 degrees )and the salivary ET(1-21) concentration was observed for the forestry workers with an abnormal cold response in their digital arteries. CONCLUSIONS: This study showed an association between salivary ET(1-21) concentration, daily and cumulative vibration exposure, and vascular disorders in the fingers of professional forestry workers. Since ET(1-21) can induce powerful and long-lasting constriction of human vessels, these findings suggest a possible role of this vasopeptide in the pathogenesis of VWF.

[Chronic hypoxia state as one of the factors of increased fluorescence of endogenous porphyrins in alive biological tissues].

The hypothesis about the influence of chronic hypoxia in soft alive tissues on the intensity of He-Ne laser-induced fluorescence of endogenous porphyrins in tissues in the red region of the optical spectrum is discussed. Some theoretical prerequisites for enormous accumulation of porphyrins in soft tissues in a number of pathological cases and diseases are presented. A method for conducting clinical experimental trials to verify the hypothesis with the use of up-to-date laser noninvasive fluorescent diagnostics is proposed. Both the theoretical reasoning and new clinical experimental data show that chronic hypoxia can be one of the factors responsible for the appearance of a strong and abnormal laser-induced fluorescent signal from biotissues in the spectrum range 600-800 nm, which is associated with abnormally high accumulation of endogenous porphyrins in tissues.