Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Alvarez P

PROVIDER: S-EPMC6668361 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Alvarez Pedro P Bogen Oliver O Levine Jon D JD

Pain 20190801 8

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. ...[more]

PMID: 31335655

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Project description: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.

Project description:Increased occurrence of Raynaud's phenomenon, neurosensory injury and carpal tunnel syndrome has been reported for more than 100 years in association with work with vibrating machines. The current risk prediction modelling (ISO-5349) for "Raynaud's phenomenon" is based on a few studies published 70 to 40 years ago. There are no corresponding risk prediction models for neurosensory injury or carpal tunnel syndrome, nor any systematic reviews comprising a statistical synthesis (meta-analysis) of the evidence.Our aim was to provide a systematic review of the literature on the association between Raynaud's phenomenon, neurosensory injuries and carpal tunnel syndrome and hand-arm vibration (HAV) exposure. Moreover the aim was to estimate the magnitude of such an association using meta-analysis.This systematic review covers the scientific literature up to January 2016. The databases used for the literature search were PubMed and Science Direct. We found a total of 4,335 abstracts, which were read and whose validity was assessed according to pre-established criteria. 294 articles were examined in their entirety to determine whether each article met the inclusion criteria. The possible risk of bias was assessed for each article. 52 articles finally met the pre-established criteria for inclusion in the systematic review.The results show that workers who are exposed to HAV have an increased risk of vascular and neurological diseases compared to non-vibration exposed groups. The crude estimate of the risk increase is approximately 4-5 fold. The estimated effect size (odds ratio) is 6.9 for the studies of Raynaud's phenomenon when including only the studies judged to have a low risk of bias. The corresponding risk of neurosensory injury is 7.4 and the equivalent of carpal tunnel syndrome is 2.9.At equal exposures, neurosensory injury occurs with a 3-time factor shorter latency than Raynaud's phenomenon. Which is why preventive measures should address this vibration health hazard with greater attention.

Dataset Information

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

Publications

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

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