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1.
Stress ; 23(1): 77-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31339402

RESUMO

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 low-grade 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.Lay summaryUsing an animal model of social stress, we identified miR-146a, miR-30c and miR-223 as potentially important gene regulatory molecules that may be involved in the stress response. Interestingly, human genotypes affecting the expression of mature miR-30c and miR-223 had a moderating effect on the association between exposure to bullying and pain. Subjects with the miR-30c rs928508 GG genotype had a significantly stronger association between exposure to bullying behaviors and pain than other subjects. The same was observed in men with the miR-223 rs3848900 G genotype, as compared to other men.

2.
Arthritis Res Ther ; 21(1): 186, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409426

RESUMO

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.

3.
BMC Res Notes ; 12(1): 547, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455415

RESUMO

OBJECTIVE: Earlier studies documenting the effect of candidate genes on recovery have seldom taken into consideration the impact of emotional distress. Thus, we aimed to assess the modifying effect of emotional distress on genetic variability as a predictor for pain recovery in lumbar radicular (LRP) and low back pain (LBP). RESULTS: The study population comprised 201 patients and mean age was 41.7 years. The significant association between MMP9 rs17576 (B = 0.71, 95% CI 0.18 to 1.24, p = 0.009) and pain recovery remained statistically significant after adjusting for pain intensity at baseline, age, gender, smoking, body mass index, pain localization and emotional distress (B = 0.68, 95% CI 0.18 to 1.18, p = 0.008). In contrast, the association between OPRM1 (B = - 0.85, 95% CI - 1.66 to - 0.05, p = 0.038) and pain recovery was abolished in the multivariate analysis (B = - 0.72, 95% CI - 1.46 to 0.02, p = 0.058). Hence, MMP9 rs17576 and emotional distress independently seem to predict persistent back pain. The predictive effect of OPRM1 rs179971 with regard to the same outcome is probably dependent on other factors including emotional processing. Trial registration The Regional Committee for Medical Research and Ethics reference number 2014/1754.


Assuntos
Dor nas Costas/fisiopatologia , Emoções , Dor Lombar/fisiopatologia , Vértebras Lombares/fisiopatologia , Adulto , Dor nas Costas/diagnóstico , Dor nas Costas/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Dor Lombar/diagnóstico , Dor Lombar/genética , Vértebras Lombares/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Medição da Dor/métodos , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco
4.
Sleep Med ; 60: 224-229, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31213395

RESUMO

BACKGROUND: Previous studies indicate that shift work tolerance may be associated with individual factors including genetic variability in the gene encoding the serotonin transporter 5-HTT (SLC6A4). The present study aimed to explore the interaction between work schedule (shift work versus non-shift work), genetic variability in SLC6A4 and insomnia symptoms. METHODS: The study was based on a national probability sample survey of 987 Norwegian employees drawn from The Norwegian Central Employee Register by Statistics Norway. Insomnia symptoms were assessed by three items reflecting problems with sleep onset, sleep maintenance, and early morning awakenings. Genotyping concerning SLC6A4 (the 5-HTTLPR S versus L and the SNP rs25531 A versus G) was carried out using a combination of gel-electrophoresis and TaqMan assay. RESULTS: Using the LALA genotype as a reference a main effect of the SS genotype (B = 0.179; 95% CI = 0.027-0.330) was found. In addition, a main effect of work schedule (0 = non shift, 1 = shift work) was found (B = 0.504; 95% CI = 0.185-0.823). The genotype x work schedule interaction was significant for all genotypes; SLA (B = -0.590; 95% CI = -0.954-0.216), LALG (B = -0.879; 95% CI = -1.342-0.415), SLG (B = -0.705; 95% CI = -1.293-0.117) and SS (B = -0.773; 95% CI = -1.177-0.369) indicating higher insomnia symptom scores among LALA-participants compared to participants with other genotypes when working shifts. CONCLUSIONS: The ability to cope with shift work is associated with the combination of the SLC6A4 variants 5-HTTLPR and SNP rs25531. Our findings demonstrated that the LALA-genotype increases the risk of insomnia symptoms among shift workers.

5.
Front Psychol ; 10: 1204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178808

RESUMO

Several lines of evidence show that systematic exposure to negative social acts at the workplace i.e., workplace bullying, results in symptoms of depression and anxiety among those targeted. However, little is known about the association between bullying, inflammatory genes and sleep problems. In the present study, we examined the indirect association between exposure to negative social acts and sleep through distress, as moderated by the miR-146a genotype. The study was based on a nationally representative survey of 1179 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to workplace bullying was measured with the 9-item version of Negative Acts Questionnaire - Revised (NAQ-R) inventory. Seventeen items from Hopkins Symptom Checklist (HSCL-25) was used to measure distress. Insomnia was assessed with three items reflecting problems with sleep onset, maintenance of sleep and early morning awakening. Genotyping with regard to miR-146a rs2910164, previously linked to inflammatory processes, was carried out using Taqman assay. The data revealed that individuals systematically exposed to negative social acts at the workplace reported higher levels of sleep problems than non-exposed individuals. Moreover, the relationship between distress induced by exposure to negative social acts and insomnia was significantly stronger for individuals with the miR-146a GG genotype. Thus, the miR-146a genotype moderated the association between distress and insomnia among individuals exposed to negative social acts. The present report support the hypothesis that inflammation could play a role in stress-induced insomnia among individuals exposed to workplace bullying.

6.
Spine (Phila Pa 1976) ; 44(13): E774-E781, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31205173

RESUMO

STUDY DESIGN: A prospective observational study with translation and psychometric analyses of a questionnaire. OBJECTIVE: Cross-cultural adaptation of the Short-Form McGill Pain Questionnaire-2 into Norwegian. SUMMARY OF BACKGROUND DATA: The different versions of the McGill Pain Questionnaire (MPQ) have been important and influential tools for pain assessment. To more reliably assess qualities of both neuropathic and non-neuropathic pain, the Short-Form MPQ was revised in 2009 (SF-MPQ-2), including seven additional descriptors. No Norwegian adaptation of the SF-MPQ-2 has been performed. METHODS: A translation of the SF-MPQ-2 was performed based on established guidelines. Forward-translations were compared and discussed in an expert workgroup. A synthesis was achieved by consensus. A backward translation was reviewed and consolidated with the forward translations to confirm linguistic equivalence. A prefinal version was tested in eight patients, who were interviewed to evaluate acceptability and comprehension of the questionnaire. Minor changes were implemented. The questionnaire was externally proofread. The final Norwegian version (NSF-MPQ-2) was tested for content and construct validity and internal consistency reliability in a population with low back-related leg pain. RESULTS: The backward translation was in good accordance with the original version. The prefinal version showed excellent acceptability and comprehension in initial patient-testing. The NSF-MPQ-2 showed satisfactory content and construct validity, including responsiveness to change, and acceptable internal consistency reliability as measured by Cronbach's alpha. A confirmatory factor analysis showed poor fit for the established four-factor structure, especially regarding the neuropathic subscale. CONCLUSION: The NSF-MPQ-2 showed excellent acceptability and comprehension, satisfactory content and construct validity, including responsiveness to change, and internal consistency reliability as measured by Cronbach's alpha. However, a confirmatory factor analysis raised concerns regarding the factor-structure in the present population. Until more evidence emerges for the four-factor solution we suggest the NSF-MPQ-2 should be used as a single measure. LEVEL OF EVIDENCE: 3.


Assuntos
Comparação Transcultural , Dor Lombar/diagnóstico , Dor Lombar/etnologia , Medição da Dor/normas , Inquéritos e Questionários/normas , Traduções , Adulto , Feminino , Seguimentos , Humanos , Perna (Membro)/patologia , Dor Lombar/psicologia , Masculino , Pessoa de Meia-Idade , Noruega/etnologia , Medição da Dor/métodos , Estudos Prospectivos , Psicometria/normas , Reprodutibilidade dos Testes
7.
Pain Rep ; 4(2): e718, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31041419

RESUMO

Introduction: Lumbar radicular pain after disk herniation is associated with local release of many inflammatory molecules from nucleus pulposus (NP) cells leaking out of the intervertebral disk. Here, we have used a rat model to investigate the role of epiregulin (EREG), a member of the epidermal growth factor (EGF) family, in this process. Methods: A protein immunoassay was chosen to confirm the release of EREG from the NP tissue. Single unit recordings were used to demonstrate the effect of recombinant EREG applied onto the dorsal nerve roots in vivo. Intracellular responses induced by recombinant EREG were studied in cultured dorsal root ganglion (DRG) cells by phosphoprotein assay. Changes in EGF receptor expression induced by NP in the DRG were examined by quantitative polymerase chain reaction. Results: The protein immunoassay showed that EREG was released from the NP tissue. Moreover, application of EREG onto the spinal dorsal nerve roots induced a decrease in the evoked responses, but an increase in spontaneous activity in the dorsal horn neurons. Interestingly, the EREG activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the DRG, a pathway previously linked to cellular growth, proliferation, and tissue regeneration. An NP-induced upregulation of the EGF receptor HER3 in the DRG was also revealed. Conclusion: Taken together, the present observations indicate that EREG may induce changes in the DRG and spontaneous activity in the pain pathways. We suggest that EREG signaling may be involved in the pathophysiological process leading to sensory deficits and neuropathic pain in patients after disk herniation.

8.
Front Psychol ; 10: 44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740075

RESUMO

Stressors in the work environment and individual dispositions among targets have been established separately as antecedents and risk factors of workplace bullying. However, few studies have examined these stressors in conjunction in order to determine personal dispositions among targets as possible moderators in the work stressor-bullying relationship. The aim of the present study was to examine multiple types of dispositional affect among targets as potential moderators in the relationship between role conflict and exposure to bullying behaviors, employing two independent cross-sectional samples. The first sample comprised 462 employees from a Norwegian sea transport organization, where trait anger and trait anxiety were included moderators. The second sample was a nationwide probability sample of the Norwegian working population and comprised 1,608 employees randomly drawn from The Norwegian Central Employee Register, where positive and negative affect were included moderators. The results showed that trait anger, trait anxiety, and negative affect strengthened the positive relationship between role conflict and reports of bullying behaviors. Positive affect did not moderate this relationship. We conclude that the association between role conflict and bullying is particularly strong for those scoring high on trait anger, trait anxiety, and negative affect.

9.
Skeletal Radiol ; 48(6): 871-879, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30255192

RESUMO

OBJECTIVE: To examine the impact of demographic, clinical, and genetic factors as well as herniated discs on 5-year development of disc degeneration in the lumbar spine, and to investigate associations between changes in lumbar degenerative findings and pain. MATERIALS AND METHODS: In 144 patients with lumbar radicular pain or low back pain, we scored disc degeneration, herniated discs, and high-intensity zones in the posterior annulus fibrosus on lumbar magnetic resonance imaging (MRI) at baseline and 5-year follow-up. Genotyping (TaqMan assay) was performed for genes encoding vitamin D receptor (VDR), collagen XIα (COL11A), matrix metalloproteinase 1/9 (MMP1/MMP9), and interleukin 1α/1RN (IL-1α/IL-1RN). Associations were analyzed using multivariate linear regression adjusted for age, sex, smoking, body mass index, and baseline scores for degenerated discs and herniated discs (when analyzing impact of baseline factors) or for pain (when analyzing associations with pain). RESULTS: Progression of disc degeneration over 5 years was significantly (p < 0.001) related to higher age and less disc degeneration at baseline, but not to sex, smoking, body mass index, herniated discs, or variants in the studied genes. No associations were identified between changes in disc degeneration or high-intensity zones and pain at 5-year follow-up. However, increased number of herniated discs over 5 years was associated with pain at rest (p = 0.019). CONCLUSIONS: Age and disc degeneration at baseline, rather than genetic factors, influenced the 5-year development of disc degeneration in patients with lumbar radicular pain or low back pain. Development of herniated discs was related to pain at rest.


Assuntos
Degeneração do Disco Intervertebral/diagnóstico por imagem , Imagem por Ressonância Magnética , Adulto , Fatores Etários , Colágeno Tipo XI/genética , Progressão da Doença , Feminino , Genótipo , Humanos , Interleucina-1/genética , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Receptores de Calcitriol/genética
10.
Brain Behav Immun ; 76: 82-96, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30419269

RESUMO

BACKGROUND: Chronic Fatigue Syndrome (CFS) is one of the most important causes of disability among adolescents while limited knowledge exists on genetic determinants underlying disease pathophysiology. METHODS: We analyzed deregulated immune-gene modules using Pathifier software on whole blood gene expression data (29 CFS patients, 18 controls). Deconvolution of immune cell subtypes based on gene expression profile was performed using CIBERSORT. Supervised consensus clustering on pathway deregulation score (PDS) was used to define CFS subgroups. Associations between PDS and immune, neuroendocrine/autonomic and clinical markers were examined. The impact of plasma norepinephrine level on clinical markers over time was assessed in a larger cohort (91 patients). RESULTS: A group of 29 immune-gene sets was shown to differ patients from controls and detect subgroups within CFS. Group 1P (high PDS, low norepinephrine, low naïve CD4+ composition) had strong association with levels of serum C-reactive protein and Transforming Growth Factor-beta. Group 2P (low PDS, high norepinephrine, high naïve CD4+ composition) had strong associations with neuroendocrine/autonomic markers. The corresponding plasma norepinephrine level delineated 91 patients into two subgroups with significant differences in fatigue score. CONCLUSION: We identified 29 immune-gene sets linked to plasma norepinephrine level that could delineate CFS subgroups. Plasma norepinephrine stratification revealed that lower levels of norepinephrine were associated with higher fatigue. Our data suggests potential involvement of neuro-immune dysregulation and genetic stratification in CFS.


Assuntos
Síndrome de Fadiga Crônica/genética , Síndrome de Fadiga Crônica/imunologia , Norepinefrina/metabolismo , Adolescente , Sistema Nervoso Autônomo/fisiopatologia , Biomarcadores/sangue , Proteína C-Reativa , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Análise por Conglomerados , Síndrome de Fadiga Crônica/metabolismo , Feminino , Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/imunologia , Humanos , Masculino , Sistemas Neurossecretores/fisiopatologia , Norepinefrina/sangue , Plasma , Transcriptoma/genética
11.
Pain ; 159(12): 2585-2592, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30130297

RESUMO

The placebo effect is considered the core example of mind-body interactions. However, individual differences produce large placebo response variability in both healthy volunteers and patients. The placebo response in pain, placebo analgesia, may be dependent on both the opioid system and the dopaminergic system. Previous studies suggest that genetic variability affects the function of these 2 systems. The aim of this study was therefore to address the interaction between the single nucleotide polymorphisms opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 on placebo analgesia. Two hundred ninety-six healthy volunteers participated in a repeated-measures experimental design where thermal heat pain stimuli were used as pain stimuli. Participants were randomized either to a placebo group receiving placebo cream together with information that the cream would reduce pain, or to a natural history group receiving the same pain stimuli as the placebo group without any application of cream or manipulation of expectation of pain levels. The results showed that the interaction between OPRM1 rs1799971 and COMT rs4680 was significantly associated with the placebo analgesic response. Participants with OPRM1 Asn/Asn combined with COMT Met/Met and Val/Met reported significant pain relief after placebo administration, whereas those with other combinations of the OPRM1 and COMT genotypes displayed no significant placebo effect. Neither OPRM1 nor COMT had any significant influence on affective changes after placebo administration. As shown in this study, genotyping with regard to OPRM1 and COMT may predict who will respond favorably to placebo analgesic treatment.


Assuntos
Catecol O-Metiltransferase/genética , Hiperalgesia , Efeito Placebo , Polimorfismo de Nucleotídeo Único/genética , Receptores Opioides mu/genética , Adulto , Método Duplo-Cego , Feminino , Marcadores Genéticos , Testes Genéticos , Voluntários Saudáveis , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/genética , Hiperalgesia/psicologia , Modelos Lineares , Masculino , Adulto Jovem
12.
Scand J Pain ; 18(1): 93-98, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29794283

RESUMO

BACKGROUND AND AIMS: Matrix metalloproteinase 9 (MMP9) is an enzyme that may affect degradation of several extracellular matrix (ECM) components in the pelvic ligaments during pregnancy. Previous studies indicate that genetic variations in the gene encoding MMP9 may affect the enzymatic activity. One such genetic variant is a single nucleotide polymorphism (SNP), rs17576 A>G. In this study we investigated whether the MMP9 SNP rs17576 A>G may be associated with increased lumbopelvic pain in 838 pregnant woman. The study was registered with ClinicalTrials.gov (NCT 00476567) on May 21, 2007. METHODS: Lumbopelvic pain-intensity was measured by visual analog scale (VAS) at two time points during pregnancy, T1 (18-22 weeks), T2 (32-36 weeks) and 3 months after delivery. Blood samples were collected at each point and SNP genotyping was carried out using predesigned TaqMan SNP genotyping assays. RESULTS: The results showed a significant association between the number of G alleles and pain-intensity in the evening at T2. The pain among G/G carriers was higher than among A/G carriers, which in turn was higher than among the A/A carriers. The most pronounced association between the G allele and pain-intensity was observed in primiparae. CONCLUSIONS: We conclude that the MMP9 rs17576 A>G polymorphism is associated with increased lumbopelvic pain-intensity during pregnancy. The present data support the hypothesis that lumbopelvic pain during pregnancy may be related to a relaxin - MMP9 - tissue remodeling mechanism. IMPLICATIONS: The present findings may be important for future mechanistic studies on how MMP9 rs17576 A>G may affect changes in the ECM components in pelvic ligaments and lumbopelvic pain-intensity during pregnancy.


Assuntos
Predisposição Genética para Doença , Dor Lombar/genética , Metaloproteinase 9 da Matriz/genética , Dor Pélvica/genética , Polimorfismo de Nucleotídeo Único , Complicações na Gravidez/genética , Adulto , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Medição da Dor , Período Pós-Parto , Gravidez , Adulto Jovem
13.
J Psychosom Res ; 106: 73-75, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29455903

RESUMO

OBJECTIVE: The association between exposure to bullying at work and subsequent pain reports is relatively well-established, but few studies have examined possible moderators of this relationship. As gender is a known risk factor for pain, with women reporting pain levels of higher intensity and longer duration, a possible gender difference in the relationship between bullying and pain has been suggested, but not sufficiently tested. The objective of the present study was therefore to examine whether gender moderates the prospective relationship between exposure to workplace bullying behaviours and subsequent subjective back and neck pain. METHODS: A national probability sample of Norwegian workers (N=1003) was collected at two time points with a six-month time-lag. Assumptions were tested using regression and moderation analyses. RESULTS: Exposure to bullying behaviours was associated with increased reports of subjective back and neck pain over time, and this relationship was moderated by gender. However, the interaction took a different form than expected, with back and neck pain increasing in response to bullying among men only, to a degree that nullified the baseline gender difference. CONCLUSION: The assumption that being female is a vulnerability factor for the development of pain in the aftermath of psychosocial stressors such as bullying was contradicted in the present study. Instead, women's relatively high baseline pain levels remain stable over time even after exposure to workplace bullying, while men's relatively low baseline pain levels increase in response to bullying, ultimately becoming tangent to the pain reported by women.


Assuntos
Dor nas Costas/psicologia , Bullying/psicologia , Cervicalgia/psicologia , Adulto , Feminino , Humanos , Masculino , Noruega , Fatores de Risco , Amostragem , Distribuição por Sexo
14.
Scand J Work Environ Health ; 44(3): 283-290, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29313869

RESUMO

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. Methods The 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. Results The 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 LALA genotype than for subjects with the SLA/LALG/SLG genotype. No significant difference between subjects with the LALA 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.


Assuntos
Bullying/psicologia , Medição da Dor/psicologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Local de Trabalho/psicologia , Adulto , Ansiedade/etiologia , Ansiedade/psicologia , Depressão/etiologia , Depressão/psicologia , Feminino , Interação Gene-Ambiente , Técnicas de Genotipagem , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
15.
Pain ; 159(1): 168-174, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968343

RESUMO

Higher levels of fear have been shown to partly explain individual differences in placebo analgesic responding. The catechol-O-methyltransferase (COMT) rs4680 Val158Met polymorphism has been associated with both increased placebo analgesia and increased fear-related behavior, in what appears to be inconsistent findings in the literature. The aim of the study was therefore to investigate placebo analgesia and fear-related processes with regard to the COMT genotype, to sort out whether the Met-allele is associated with increased placebo analgesia or increased fear of pain (FOP). A 3 Group (Emla, placebo and natural history) by 5 Test (2 pretest, 3 posttests) mixed design was used (N = 223). A contact heat-evoked stimulator was used to induce pain, and FOP was quantified with the Fear of Pain Questionnaire-III. Saliva was obtained for genotyping. As expected, we observed a significant interaction of test by group (P < 0.01), with lower pain report in the placebo group compared with the natural history group (P < 0.01). There was a main effect of the COMT genotype on fear of medical pain (P = 0.032), and Met-allele carriers reported significantly higher fear of medical pain compared with the Val-allele (P = 0.044). We observed no effect of the COMT genotype on mean pain-level report or placebo analgesia. Thus, we conclude that the Met-allele seems to be associated with the negative emotional process of fear, but not with placebo analgesia.


Assuntos
Catecol O-Metiltransferase/genética , Medo/fisiologia , Genótipo , Dor/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Analgesia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Dor/psicologia , Medição da Dor , Efeito Placebo
16.
Subst Use Misuse ; 53(4): 574-584, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28910176

RESUMO

BACKGROUND: Although alcohol use can have detrimental effects for employees, little is known about the prevalence, distribution, and correlates in the Norwegian workforce. AIMS: To determine the overall and the work-related prevalence of weekly alcohol use, and to establish associations between psychosocial work stressors and alcohol use among Norwegian employees. METHODS: Data were from a 2015 national probability sample of 1,608 Norwegian employees (response rate 32%). Job demands, lack of job control, role expectations, workplace bullying, and leadership were examined as correlates of several dimensions of alcohol use. RESULTS: Average weekly alcohol consumption was 4.28 units (SD = 7.91). Male workers reported significantly higher consumption than female workers. Also, 2.6% of male and 2.0% of female workers reported problematic alcohol use. Only 0.1% of workers reported weekly alcohol use before the workday, 0.4% reported weekly use during the workday, 20.1% reported weekly use after ending the work day, and 80% reported use during weekends/days off. Alcohol intake increased with age, but was not related to marital status, educational level, work schedule, or leadership position. Problematic alcohol use was related to job demands and workplace bullying. Alcohol use after work was positively related to lack of job control and role ambiguity and negatively related to bullying. Conclusions/importance: Weekly alcohol use before and during the workday is not prevalent among Norwegian workers. Interventions to reduce job demands and workplace bullying may reduce problematic alcohol intake, whereas increasing job control and reducing role ambiguity may reduce after work use.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Estresse Psicológico/psicologia , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Prevalência , Fatores de Risco , Fatores Sexuais , Adulto Jovem
17.
Front Psychol ; 8: 1953, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163321

RESUMO

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.

18.
Cytokine ; 97: 181-186, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28651128

RESUMO

Lumbar radicular pain after disc herniation may be associated with release of pro-inflammatory cytokines from nucleus pulposus (NP) tissue. In the present study we examined the role of interferon-γ (IFN-γ) and cluster of differentiation 68 (CD68) in the acute phase of this process. First, in an animal model mimicking the clinical situation after disc herniation, the role of IFN-γ close to the dorsal nerve roots was studied. Next, in patients with lumbar radicular pain due to disc herniation, we examined how two single nucleotide polymorphisms (SNPs; rs2069705 and rs2069718) are important for the IFN-γ expression influenced the pain behavior. The animal data demonstrated a significant increase in the nociceptive activity at the spinal level after local application of NP and IFN-γ onto the dorsal nerve roots. A positive correlation between IFN-γ and CD68 in the NP tissue was also demonstrated. In the patients, a significant increase in Oswestry Disability Index (ODI) score was observed in carriers of the IFN-γ SNPs; rs2069705 A and rs2069718 G alleles. The present data suggest that IFN-γ close to the dorsal nerve roots may contribute to the pathogenesis, the nociceptive activity and the pain behavior following lumbar disc herniation.


Assuntos
Interferon gama/genética , Deslocamento do Disco Intervertebral/imunologia , Dor Lombar/etiologia , Vértebras Lombares , Adolescente , Adulto , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Citocinas/análise , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/fisiopatologia , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/imunologia , Polimorfismo de Nucleotídeo Único , Ratos , Regulação para Cima , Adulto Jovem
19.
J Transl Med ; 15(1): 89, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28460630

RESUMO

BACKGROUND: Previous 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. METHODS: Single 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. RESULTS: In 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). CONCLUSIONS: Our 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 2014/1725.


Assuntos
Exossomos/metabolismo , Deslocamento do Disco Intervertebral/complicações , Vértebras Lombares/patologia , MicroRNAs/metabolismo , Dor/etiologia , Dor/genética , Adulto , Animais , Exossomos/ultraestrutura , Feminino , Humanos , Deslocamento do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/fisiopatologia , Vértebras Lombares/fisiopatologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Ratos Endogâmicos Lew , Recuperação de Função Fisiológica , Fatores de Risco , Regulação para Cima/genética , Escala Visual Analógica , Adulto Jovem
20.
Pain ; 158(8): 1456-1460, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28471875

RESUMO

Previous data suggest that persistent back pain may be associated with genetic variability. In this study, we assessed the correlation between 8 genetic polymorphisms (VDR, COL11, MMP1, MMP9, IL-1α, IL-1RN, OPRM1, COMT) and pain recovery in patients with low back pain (LBP) and lumbar radicular pain (LRP). In total, 296 patients with LBP or LRP were followed for 5 years. The patients underwent standardized clinical examination and completed pain and function questionnaires. Univariate linear regression associations with P values <0.1 were included in the multivariable analysis, adjusting for pain intensity at baseline, age, sex, smoking, body mass index, and LBP or LRP. Pain intensity at 5-year follow-up was associated with VDR rs731236 (B = -0.5, 95% confidence interval [CI] -0.9 to -0.1, P = 0.017), MMP9 rs17576 (B = 0.5, 95% CI 0.1-0.9, P = 0.022), and OPRM1 rs1799971 (B = -0.8, 95% CI -1.4 to -0.2, P = 0.006) in the univariate analyses. MMP9 rs17576 and OPRM1 rs1799971 remained significant (B = 0.4, 95% CI 0.05-0.8, P = 0.026 and B = -0.8, 95% CI -1.3 to -0.2, P = 0.007) in the multivariable model. Thus, the data demonstrated that the rare allele of MMP9 rs17576 was associated with poor pain recovery, whereas the rare allele of OPRM1 rs1799971 was associated with better pain recovery at 5-year follow-up in the LBP and LRP patients. In particular, the present study suggested that the OPRM1 rs179971 A>G in men was associated with better long-term pain recovery. In men, the OPRM1 rs1799971 explained 4.7% of the variance of pain intensity. We conclude that the MMP9 rs17576 and OPRM1 rs1799971 genotypes may affect 5-year recovery in patients with LBP and LRP.


Assuntos
Predisposição Genética para Doença , Dor Lombar/genética , Vértebras Lombares/fisiopatologia , Medição da Dor , Polimorfismo de Nucleotídeo Único/genética , Adulto , Feminino , Genótipo , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/fisiopatologia , Dor Lombar/diagnóstico , Região Lombossacral/fisiopatologia , Masculino , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Receptores Opioides mu/genética
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