BackgroundPrevious findings have demonstrated that lumbar radicular pain after disc herniation may be associated with up-regulation of inflammatory mediators. In the present study we examined the possible role of extracellular microRNAs (miRs) in this process.MethodsSingle unit recordings, isolation of exosome-like vesicles, electron microscopy, nanoparticle tracking analysis, western blot analysis and qPCR were used in rats to demonstrate the effect of nucleus pulposus (NP) applied onto the dorsal nerve roots. ELISA and qPCR were used to measure the level of circulating IL-6 and miRs in a 1-year observational study in patients after disc herniation.ResultsIn the rats, enhanced spinal cord nociceptive responses were displayed after NP applied onto the dorsal nerve roots. An increased release of small non-coding RNAs, including miR-223, miR-760 and miR-145, from NP in exosome-like vesicles was demonstrated. In particular, the NP expression of miR-223, which inhibited the nociceptive spinal signalling, was increased. In the patients, increased extracellular miR-223 was also verified in the acute phase after disc herniation. The increased miR-223 expression was, however, only observed in those who recovered (sex, age and smoking were included as covariates).ConclusionsOur findings suggest that miR-223, which can be released from the NP after disc herniation, attenuates the neuronal activity in the pain pathways. Dysregulation of miR-223 may predict chronic lumbar radicular pain. Trial registration/ethics REK 2014/1725Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1194-8) contains supplementary material, which is available to authorized users.

In the context of workplace bullying, the ability to defend refers to whether or not a target feels able to deal with those negative behaviors that typically constitute bullying. The aim of this study was to determine whether the perceived ability to defend oneself moderates the association between exposure to bullying behaviors at work and symptoms of anxiety as predicted by the definition of workplace bullying. It was hypothesized that exposure to bullying behaviors would be more strongly related to symptoms of anxiety among targets feeling unable to defend oneself than among targets who do feel that they are able to defend themselves in the actual situation. This survey study was based on a probability sample of 1,608 Norwegian employees (response rate 32%). Only respondents exposed to at least one bullying behavior were included (N = 739). In contrast to hypothesis, the findings showed that ability to defend only had a protective effect on the relationship between exposure to bullying behaviors and anxiety in cases of low exposure. In cases of high exposure, there was a stronger increase in anxiety among employees able to defend themselves than among those who generally felt unable to defend. Hence, the ability to defend against exposure to bullying behaviors does not seem to protect high-exposed targets against symptoms of anxiety. Organization should therefore intervene against bullying in early stages rather than relying on the individual resilience of those exposed.

Cerebral lesions were studied in 2 methanol-poisoned patients using conventional magnetic resonance imaging (MRI). In 1 patient, diffusion-weighted MRI (DWI) was also performed. In this patient, conventional MRI showed symmetrical, bilateral increased signal in the lentiform nuclei, involving predominantly putamina, but also extending into the corona radiata, centrum semiovale and subcortical white matter. DWI showed decreased diffusion, which most probably reflects cytotoxic edema. In the other patient, fluid attenuated-inversion recovery (FLAIR) and T2-weighted images showed hyperintensity in the putamina, characteristic of post-necrotic changes.

Jacobsen DP, Nielsen MB, Einarden S, Gjerstad J. Negative social acts and pain: evidence of a workplace bullying and 5-HTT genotype interaction. Scand J Work Environ Health. 2018:44(3):283-290. doi:10.5271/sjweh.3704 Objectives Long-term exposure to systematic negative acts at work, usually labeled workplace bullying, is a prevalent problem at many workplaces. The adverse effects of such exposure may range from psychological symptoms, such as depression and anxiety to somatic ailments like cardiovascular disease and musculoskeletal complaints. In this study, we examined the relationships among exposure to negative acts, genetic variability in the 5-HTT gene SLC6A4 and pain. MethodsThe study was based on a nationally representative survey of 987 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to bullying in the workplace was measured with the 9-item version of the Negative Acts Questionnaire -Revised (NAQ-R) inventory. Pain was rated using an 11-point (0-10) numeric rating scale (NRS). Genotyping with regard to SLC6A4 was carried out using a combination of gel-electrophoresis and TaqMan assay. ResultsThe data revealed a significant interaction between exposure to negative acts and the SLC6A4 genotype with regard to pain (linear regression with 5000 resamples; age, sex, tobacco use and education were included as covariates). The relationship between negative acts and pain intensity was significantly stronger for subjects with the L A L A genotype than for subjects with the SL A /L A L G /SL G genotype. No significant difference between subjects with the L A L A genotype and SS genotype was observed.Conclusions Our data demonstrated that the relationship between bullying and pain was modified by the 5-HTT genotype, ie, genetic variation in SLC6A4. The association between negative acts and health among vulnerable individuals appeared more potent than previously reported.Key terms polymorphism; psychosocial; rs23351; serotonin transporter; SLC6A; 5-HTTLPR. Exposure to systematic negative social acts at work, usually labeled workplace bullying, is a prevalent issue in contemporary working life, affecting approximately 15% of adults globally (1). Several lines of evidence demonstrate that exposure to such bullying is a major predictor of impaired health and well-being among those targeted (2, 3). The adverse effects of bullying is well documented and range from psychological symptoms, such as depression and anxiety (4, 5), to somatic ailments like cardiovascular disease (6) and musculoskeletal complaints (7). Exposure to bullying is also associated with increased risk of sickness absence (8) and disability retirement (9).While exposure to bullying in the workplace is a risk factor for pain (10, 11), pain may also be determined by the individuals psychological profile and genetic susceptibility (12). Interestingly, as much as 60% (range 25-60%) of the variance in experimental pain may be explained by genetic variability (13). Thus, pain perception is subject to la...

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Background Previous studies suggest that regulatory microRNAs (miRs) may modulate neuro-inflammatory processes. The purpose of the present study was to examine the role of miR-17 following intervertebral disc herniation. Methods In a cohort of 97 patients with leg pain and disc herniation verified on MRI, we investigated the association between circulating miR-17 and leg pain intensity. A rat model was used to examine possible changes in miR-17 expression in nucleus pulposus (NP) associated with leak of NP tissue out of the herniated disc. The functional role of miR-17 was addressed by transfection of miR-17 into THP-1 cells (human monocyte cell line). Results An association between the level of miR-17 in serum and the intensity of lumbar radicular pain was shown. Up-regulation of miR-17 in the rat NP tissue when applied onto spinal nerve roots and increased release of TNF following transfection of miR-17 into THP-1 cells were also observed. Hence, our data suggest that miR-17 may be involved in the pathophysiology underlying lumbar radicular pain after disc herniation. Conclusions We conclude that miR-17 may be associated with the intensity of lumbar radicular pain after disc herniation, possibly through a TNF-driven pro-inflammatory mechanism. Electronic supplementary material The online version of this article (10.1186/s13075-019-1967-y) contains supplementary material, which is available to authorized users.

Background: Previous studies suggest that persistent exposure to social stress in mammals may be associated with multiple physiological effects. Here, we examine the effects of social stress in rats, i.e. repeated social defeat, on behavior, hypothalamic-pituitary-adrenal (HPA)-axis and immune system. Methods: A resident-intruder paradigm, where an intruder rat was exposed to social stress by a dominant resident rat for 1 hour each day for 7 consecutive days was used. The day after the last stress exposure in the paradigm the data were analyzed. Variation in social interaction was observed manually, whereas locomotion was analyzed off-line by a purpose-made software. Gene expression in the pituitary gland, adrenal gland and myeloid cells isolated from the spleen was measured by qPCR. Results: The exposure to social stress induced decreased weight gain and increased locomotion. An increased nuclear receptor subfamily group C number 1 (NR3C1) expression in the pituitary gland was also shown. In myeloid cells harvested from the spleen, we observed decreased expression of the β 2-adrenergic receptor (ADRB2) and β-arrestin-2 (ARRB2), but increased expression of interleukin-6 (IL-6). Subsequent analyses in the same cells showed that ARRB2 was negatively correlated with IL-6 following the stress exposure. Conclusion: Our results show that that the experience of social stress in the form of repeated social defeat in rats is a potent stressor that in myeloid cells in the spleen promotes persistent inflammatory changes. Future research is needed to examine whether similar inflammatory changes also can explain the impact of social stress, such as bullying and harassment, among humans.

Prolonged exposure to bullying behaviors may give rise to symptoms such as anxiety, depression and chronic pain. Earlier data suggest that these symptoms often are associated with stress-induced lowgrade systemic inflammation. Here, using data from both animals and humans, we examined the moderating role of microRNAs (miRNAs, miRs) in this process. In the present study, a resident-intruder paradigm, blood samples, tissue harvesting and subsequent qPCR analyses were used to screen for stress-induced changes in circulating miRNAs in rats. The negative acts questionnaire (NAQ), TaqMan assays and a numeric rating scale (NRS) for pain intensity were then used to examine the associations among bullying behaviors, relevant miRNA polymorphisms and pain in a probability sample of 996 Norwegian employees. In rats, inhibited weight gain, reduced pituitary POMC expression, adrenal Nr3c1 mRNA downregulation, as well as increased miR-146a, miR-30c and miR-223 in plasma were observed following 1 week of repeated exposure to social stress. When following up the miRNA findings from the animal study in the human working population, a stronger relationship between NAQ and NRS scores was observed in subjects with the miR-30c GG genotype (rs928508) compared to other subjects. A stronger relationship between NAQ and NRS scores was also seen in men with the miR-223 G genotype (rs3848900) as compared to other men. Our findings show that social stress may induce many physiological changes including changed expression of miRNAs. We conclude that the miR-30c GG genotype in men and women, and the miR-223 G genotype in men, amplify the association between exposure to bullying behaviors and pain.