Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort.

ABSTRACT: We aimed to investigate the genetic associations of neuropathic pain in a deeply phenotyped cohort. Participants with neuropathic pain were cases and compared with those exposed to injury or disease but without neuropathic pain as control subjects. Diabetic polyneuropathy was the most common aetiology of neuropathic pain. A standardised quantitative sensory testing protocol was used to categorize participants based on sensory profile. We performed genome-wide association study, and in a subset of participants, we undertook whole-exome sequencing targeting analyses of 45 known pain-related genes. In the genome-wide association study of diabetic neuropathy (N = 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P = 3.55 × 10-8). Gene-based analysis revealed significant associations between LHX8 and TCF7L2 and neuropathic pain. Polygenic risk score for depression was associated with neuropathic pain in all participants. Polygenic risk score for C-reactive protein showed a positive association, while that for fasting insulin showed a negative association with neuropathic pain, in individuals with diabetic polyneuropathy. Gene burden analysis of candidate pain genes supported significant associations between rare variants in SCN9A and OPRM1 and neuropathic pain. Comparison of individuals with the "irritable" nociceptor profile to those with a "nonirritable" nociceptor profile identified a significantly associated variant (rs72669682, P = 4.39 × 10-8) within the ANK2 gene. Our study on a deeply phenotyped cohort with neuropathic pain has confirmed genetic associations with the known pain-related genes KCNT2, OPRM1, and SCN9A and identified novel associations with LHX8 and ANK2, genes not previously linked to pain and sensory profiles, respectively.

Overweight and obesity as risk factors for chronic low back pain: a new follow-up in the HUNT Study.

BACKGROUND: Numerous studies have examined associations between overweight and obesity and risk of low back pain (LBP), but the exact magnitude of these associations is not yet clear. The purpose of this work was to assess such sex-specific associations in a community-based setting in Norway, taking into account potential relationships with other risk factors. METHODS: A cohort study was conducted combining data from two waves of the Trøndelag Health Study, HUNT3 (2006-2008) and HUNT4 (2017-2019). Separate analyses were performed of risk of chronic LBP in HUNT4 among 14,775 individuals without chronic LBP in HUNT3, and of recurrence or persistence in HUNT4 among 5034 individuals with chronic LBP in HUNT3. Relative risks were estimated in generalised linear models for overweight and obesity compared to normal weight. Body size classification was based on values of BMI computed from measurements of height and weight. Chronic LBP was defined as LBP persisting at least 3 months during last year. RESULTS: After adjustment for age, smoking, physical activity in leisure time and work activity, analysis of risk among women produced relative risks 1.11 (95% CI 1.00-1.23) for overweight, 1.36 (95% CI 1.20-1.54) for obesity class I and 1.68 (95% CI 1.42-2.00) for obesity classes II-III. Relative risks among men were 1.10 (95% CI 0.94-1.28) for overweight, 1.36 (95% CI 1.13-1.63) for obesity class I and 1.02 (95% CI 0.70-1.50) for obesity classes II-III, the last estimate being based on relatively few individuals. Analyses of recurrence or persistence indicated similar relationships but with smaller magnitude of relative risks and no drop in risk among obesity classes II-III in men. The change in BMI from HUNT3 to HUNT4 hardly differed between individuals with and without chronic LBP in HUNT3. CONCLUSIONS: Risk of chronic LBP increases with higher values of BMI in both sexes, although it is uncertain whether this applies to very obese men. Very obese women carry a particularly large risk. Probabilities of recurrence or persistence of chronic LBP among those already afflicted also increase with higher values of BMI. Adjustment for other factors does not influence relationships with overweight and obesity to any major extent.

Relationship between migraine and epilepsy in a large population-based cohort: The HUNT Study.

BACKGROUND AND PURPOSE: Several studies have reported substantial comorbidity between epilepsy and migraine. Most of these were based on clinical cohorts or used unvalidated diagnostic instruments. Our study re-examined this association in a large general population cohort using validated diagnoses for both disorders. METHODS: A total of 65,407 participants (≥20 years old) from HUNT (the Trøndelag Health Study) were classified for migraine and nonmigraine headache using a validated questionnaire. Medical record review was used to validate and classify epilepsy in 364 participants (cases), who were compared with 63,298 participants without epilepsy (controls). The association between epilepsy and migraine was analysed using logistic regression adjusted for sex and age. RESULTS: Patients with epilepsy had no increased prevalence of migraine (odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.68-1.33) or nonmigraine headache (OR = 1.18, 95% CI = 0.93-1.50) compared to controls. When stratified by headache frequency, epilepsy was associated with a higher prevalence of migraine with highly frequent headache (≥7 days/month; OR = 1.73, 95% CI = 1.08-2.78). CONCLUSIONS: Migraine was equally common in people with and without epilepsy. Patients with epilepsy who suffered from migraine were more prone to having highly frequent migraine.

Prevalence and risk of psychiatric disorders in young people: prospective cohort study exploring the role of childhood trauma (the HUNT study).

BACKGROUND: Better knowledge about childhood trauma as a risk factor for psychiatric disorders in young people could help strengthen the timeliness and effectiveness of prevention and treatment efforts. AIMS: To estimate the prevalence and risk of psychiatric disorders in young people following exposure to childhood trauma, including interpersonal violence. METHOD: This prospective cohort study followed 8199 adolescents (age range 12-20 years) over 13-15 years, into young adulthood (age range 25-35 years). Data about childhood trauma exposure from adolescents participating in the Trøndelag Health Study (HUNT, 2006-2008) were linked to data about subsequent development of psychiatric disorders from the Norwegian Patient Registry (2008-2021). RESULTS: One in four (24.3%) adolescents were diagnosed with a psychiatric disorder by young adulthood. Regression analyses showed consistent and significant relationships between childhood exposure to both interpersonal violence and other potentially traumatic events, and subsequent psychiatric disorders and psychiatric comorbidity. The highest estimates were observed for childhood exposure to two or more types of interpersonal violence (polyvictimisation), and development of psychotic disorders (odds ratio 3.41, 95% CI 1.93-5.72), stress and adjustment disorders (odds ratio 4.20, 95% CI 3.05-5.71), personality disorders (odds ratio 3.98, 95% CI 2.70-5.76), alcohol-related disorders (odds ratio 3.28, 95% CI 2.06-5.04) and drug-related disorders (odds ratio 4.67, 95% CI 2.87-7.33). CONCLUSIONS: These findings emphasise the importance of integrating knowledge about childhood trauma as a potent risk factor for psychopathology into the planning and implementation of services for children, adolescents and young adults.

Lifestyle and metabolic factors affect risk for meningioma in women: a prospective population-based study (The Cohort of Norway).

Background: Meningioma is the most common primary brain tumor, with a clear preponderance in women. Obesity is considered a risk factor for the development of meningioma. Obesity is also the clinical hallmark of metabolic syndrome, characterized by glucose intolerance, dyslipidemia, and hypertension. Lifestyle and metabolic factors directly impact overweight and obesity and are therefore potential risk factors for meningioma development. The aim of this study is to assess lifestyle and metabolic factors for meningioma risk in women. Methods: The Cohort of Norway (CONOR) is a nationwide health survey, conducted between 1994 and 2003, including anthropometric measures, blood tests, and health questionnaires. Linkage to the National Cancer Registry enabled the identification of intracranial meningioma during follow-up until December 2018. Results: A total of 81,652 women were followed for a combined total of 1.5 million years, and 238 intracranial meningiomas were identified. Increasing levels of physical activity (HR 0.81; 95% CI 0.68-0.96; p trend <0.02) and parity (HR 0.83; 95% CI 0.71-0.97; p trend <0.03) were negatively associated with meningioma risk. Diabetes mellitus or glucose intolerance increased the risk for meningioma (HR 2.54; 95% CI 1.60-4.05). Overweight and obesity were not associated with meningioma risk, nor was metabolic syndrome. However, participants without metabolic dysfunction had a reduced meningioma risk, while participants with all five metabolic factors present had a 4-fold risk increase for meningioma (HR 4.28; 95% CI 1.34-13.68). Conclusion: Lifestyle factors seem to significantly influence meningioma risk. However, disentangling the complex associations and interactions between factors for meningioma risk will be a challenging task for future studies.

Health care workers' qualitative descriptions of ethically challenging situations evoking moral distress during Covid-19.

Background: The high public demand for healthcare services during the COVID-19 pandemic and strict infection control measures, coupled with threat of severe illness and death, and limited resources, led to many healthcare workers (HCWs) experiencing ethically challenging situations (ECSs). Objective: To systematically explore first-hand accounts of ECS-evoking moral distress among HCWs during this public health emergency. Research design: This was an open cohort study. All participants were asked whether they had been in ECS-evoking moral distress during the pandemic. Those who had were asked to describe these situations. Answers were systematically analyzed according to three levels of root causes for ECSs, using thematic analysis. Participants and research context: In January 2022, 977 HCWs from four Norwegian university hospitals participated. Ethical considerations: The study received ethical approval from the Norwegian Ethical Review Authority (No. 130944). Results: In total, 508 participants (52%) reported that they had experienced ECS-evoking moral distress during the pandemic, whereof 323 provided a qualitative description. We found that while a few reported ECSs caused at the patient level, and some described situations at the unit/team level, the vast majority reported situations caused at the system level, predominantly related to resource scarcity, particularly poor staffing. Conclusion: Our findings strongly indicate that efforts to mitigate moral distress among HCWs should be targeted at the system level. More specifically, the study findings highlight resource limitations, particularly poor staffing, as a major cause of moral distress during the pandemic.

Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study.

INTRODUCTION: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.

Correction: Clinical improvement after surgery for degenerative cervical myelopathy; A comparison of Patient-Reported Outcome Measures during 12-month follow-up.

[This corrects the article DOI: 10.1371/journal.pone.0264954.].

Childhood trauma and the use of opioids and other prescription analgesics in adolescence and young adulthood: The HUNT Study.

ABSTRACT: Opioid and nonopioid analgesics are commonly prescribed to young people to alleviate pain. Even short-term prescriptions increase the risk of persistent use and future misuse of potent analgesics, such as opioids. Childhood trauma exposure has been found to be related to pain conditions and to using more prescription analgesics. This large, prospective cohort study aimed to investigate the association of a broad range of childhood trauma exposures with prescription rates for opioid and nonopioid analgesics in adolescence and young adulthood. Self-reported data on childhood trauma exposures from adolescents (aged 13-19 years) who participated in the Young-HUNT3 Study (2006-2008, n = 8199) were linked to data from the Norwegian Prescription Database (NorPD, 2004-2021). We found that exposure to childhood trauma was consistently associated with higher prescription rates for opioids throughout adolescence and young adulthood. The highest incidence rate ratio (IRR) in adolescence was observed for sexual abuse (IRR 1.63, confidence interval [CI] 1.19-2.23). In young adulthood, the highest IRR was observed for physical violence (2.66, CI 2.27-3.12). The same overall pattern was observed for nonopioid analgesics. The more frequent prescriptions of opioid and nonopioid analgesics to participants exposed to childhood trauma suggests a higher symptom load of pain causing them to seek professional help with pain relief. Receiving potent analgesics is not without risk, and the likelihood of misuse may be elevated among trauma-exposed individuals. A trauma-informed approach to pain could be vital for guiding clinicians to the most effective and least harmful treatment for each patient.

Problematic alcohol use in young adults exposed to childhood trauma: The Trøndelag Health (HUNT) Study.

Problematic alcohol use (PAU) severely impacts the health, functioning, and long-term prospects of young people. Prior research indicates that childhood trauma exposure may be an important risk factor for PAU, but few longitudinal studies have looked at how specific trauma types influence this risk. The aim of this study was to investigate the association between childhood trauma exposure and PAU in a large, population-based cohort of young people. The study sample included 1,913 adolescents who participated in the Trøndelag Health Study (HUNT) between 2006 and 2008 (age range: 12-20) and completed follow-up 10 years later as young adults (age range: 22-32). The results revealed an increased risk of PAU in young adults exposed to childhood trauma, especially direct physical violence, OR = 2.38, [95% CI 1.56, 3.64]. Young adults who had witnessed violence, OR = 1.55, [95% CI 1.11, 2.17], or experienced an accident, disaster, or other traumatic event, OR = 1.60, [95% CI 1.19, 2.15], also had higher odds of PAU compared to those without such experiences. These associations remained consistent after adjusting for symptoms of headaches and pain as well as posttraumatic and general psychological distress as reported by the participants in adolescence. Future prevention efforts targeting PAU among adolescents and young adults should address violence and other trauma exposure as potential drivers of problematic drinking.

Longitudinal Relationship Between Reduced Modic Change Edema and Disability and Pain in Patients With Chronic Low Back Pain.

STUDY DESIGN: Secondary analyses of a randomized trial [Antibiotics In Modic changes (MCs) study]. OBJECTIVE: To assess whether or not reduced MC edema over time is related to reduced disability and pain in patients with chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: It is not clear whether or not reduced MC edema implies improved clinical outcomes. PATIENTS AND METHODS: Linear regression was conducted separately in 2 subgroups with MC edema at baseline on short tau inversion recovery (STIR) or T1/T2-weighted magnetic resonance imaging, respectively. Independent variable: reduced edema (yes/no) at 1 year on STIR or T1/T2-series, respectively. Dependent variable: 1-year score on the Roland-Morris Disability Questionnaire (RMDQ), Oswestry Disability Index (ODI), or 0 to 10 numeric rating scale for LBP intensity, adjusted for the baseline score, age, smoking, body mass index, physical workload, and baseline edema on STIR (STIR analysis only). Post hoc, we, in addition, adjusted all analyses for baseline edema on STIR, treatment group (amoxicillin/placebo), and prior disc surgery-or for disc degeneration. RESULTS: Among patients with MC edema on STIR at baseline (n = 162), reduced edema on STIR was not significantly related to the RMDQ ( B : -1.0, 95% CI: -2.8, 0.8; P = 0.27), ODI ( B :-1.4, 95% CI: -5.4, 2.6; P = 0.50), or LBP intensity scores ( B : -0.05, 95% CI: -0.8, 0.7; P = 0.90) after 1 year. Among patients with MC edema on T1/T2-series at baseline (n = 116), reduced edema on T1/T2 ( i.e ., reduced volume of the type 1 part of MCs) was not significantly related to RMDQ ( B: -1.7, 95% CI: -3.8, 0.3; P = 0.10) or ODI score ( B : -2.3, 95% CI: -7.1, 2.5; P = 0.34) but was significantly related to LBP intensity at 1 year ( B : -0.9, 95% CI: -1.8, -0.04; P = 0.04; correlation coefficient: 0.24). The post hoc analyses supported these results. CONCLUSION: Reduced MC edema over 1 year was not significantly associated with pain-related disability but was (on T1/T2-series) significantly but weakly related to reduced LBP intensity. LEVEL OF EVIDENCE: Level 3.

Killing pain? A prospective population-based study on trauma exposure in childhood as predictor for frequent use of over-the-counter analgesics in young adulthood. The HUNT study.

Frequent and increasing use of over-the-counter analgesics (OTCA) is a public health concern. Pain conditions and psychological distress are related to frequent OTCA use, and as exposure to potentially traumatic events (PTE) in childhood appears to increase risk of experiencing such symptoms, we aimed to assess childhood PTEs and related symptoms in adolescence as predictors for frequent OTCA use in young adulthood. Prospective population survey data were used (n = 2947, 59.1% female, 10-13 years follow-up). Exposure to PTEs, symptoms of post-traumatic stress, anxiety and depression, musculoskeletal pain and headache were assessed in adolescence (13-19 years). Use of OTCA was assessed in young adulthood (22-32 years) and use of OTCA to treat musculoskeletal pain and headache served as separate outcomes in ordinal logistic regression analyses. Overall, exposure to childhood PTEs, particularly direct interpersonal violence, was significantly and consistently related to more frequent use of OTCA to treat musculoskeletal pain and headaches in young adulthood. Adjusting for psychological symptoms and pain attenuated associations, indicating that these symptoms are of importance for the relationship between traumatic events and OTCA use. These findings emphasize the need to address symptomatology and underlying causes at an early age.

Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes.

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment.

Cytokine Patterns as Predictors of Antibiotic Treatment Effect in Chronic Low Back Pain with Modic Changes: Subgroup Analyses of a Randomized Trial (AIM Study).

Objective: Randomized trials testing the effect of antibiotics for chronic low back pain (LBP) with vertebral bone marrow changes on MRI (Modic changes) report inconsistent results. A proposed explanation is subgroups with low grade discitis where antibiotics are effective, but there is currently no method to identify such subgroups. The objective of the present study was to evaluate whether distinct patterns of serum cytokine levels predict any treatment effect of oral amoxicillin at one-year follow-up in patients with chronic low back pain and Modic changes at the level of a previous lumbar disc herniation. Design: We used data from an overpowered, randomized, placebo-controlled trial (the AIM study) that tested 100 days of oral 750 mg amoxicillin vs placebo three times daily in hospital outpatients with chronic (>6 months) LBP with pain intensity ≥5 on a 0-10 numerical rating scale and Modic changes type 1 (oedema type) or 2 (fatty type). We measured serum levels of 40 inflammatory cytokines at baseline and analysed six predefined potential predictors of treatment effect based on cytokine patterns in 78 randomized patients; three analyses with recursive partitioning, one based on cluster analysis and two based on principal component analyses. The primary outcome was the Roland-Morris Disability Questionnaire score at one-year follow-up in the intention to treat population. The methodology and overall results of the AIM study were published previously. Results: The 78 patients were 25-62 years old and 47 (60%) were women. None of the three recursive partitioning analyses resulted in any suggested subgroups. Of all main analyses, the largest effect estimate (mean difference between antibiotic and placebo groups) was seen in a subgroup not predefined as of main interest (Cluster category 3+4; -2.0, 95% CI: -5.2-1.3, RMDQ points; p-value for interaction 0.54). Conclusion: Patterns of inflammatory serum cytokine levels did not predict treatment effect of amoxicillin in patients with chronic LBP and Modic changes. Clinical Trial Registration Number: ClinicalTrials.gov (identifier: NCT02323412).

Musculoskeletal pain is not clearly associated with the risk of anterior cruciate ligament reconstruction in adolescents.

Objectives: The purpose of this study was to investigate whether self-reported musculoskeletal pain (MSP) was associated with a future anterior cruciate ligament reconstruction (ACLR). Methods: In this population-based prospective cohort study, we included 8087 participants from the adolescent part of the Trøndelag Health Study (Young-HUNT) in Norway. The exposure was self-reported MSP from the Young-HUNT3 study (2006-2008), which was categorised into two MSP load groups (high MSP and low MSP) based on frequency and number of pain sites. The outcome was ACLRs recorded in the Norwegian Knee Ligament Register between 2006 and 2019. Logistic regression was used to investigate association between MSP load and ACLR, given as ORs with 95% CIs. All tests were two-sided and p values of ≤0.05 were considered statistically significant. Results: 8087 adolescents were included. We identified a total of 99 ACLRs, with 6 ACLRs (0.9%) in adolescents who reported high MSP load and 93 ACLRs (1.3%) among those who reported low MSP load. Adolescents reporting high MSP load had 23% lower odds of an ACLR (OR 0.77, 95% CI 0.31 to 1.91) compared with adolescents with low MSP load. However, the CIs were very wide. Conclusion: Self-reported high MSP load in adolescents was not associated with increased risk of future ACLR. Although the number of participants was high, the relatively few cases of ACLR mean that we cannot be conclusive about the presence or absence of an association.

"I've kept going" - a multisite repeated cross-sectional study of healthcare workers' pride in personal performance during the COVID-19 pandemic.

BACKGROUND: For healthcare workers, working through a pandemic may include both challenges, such as coping with increased demands and a lack of control, and rewards, such as experiencing a sense of achievement and meaningfulness. In this study, we explore the accomplishments healthcare workers themselves are proud of achieving at work, in order to elucidate the positive aspects of working through a pandemic. METHODS: In June 2020 (T1), December 2020 (T2), and May 2021 (T3), healthcare workers (n = 1,996) at four Norwegian hospitals participated in a web-based survey assessing job strain, psychological health, and support during the pandemic. The survey included the open-ended question "During the past two weeks, what have you been feeling proud of achieving at work?". Responses (1,046) to this item were analyzed using conventional content analysis, which resulted in 13 subthemes under 6 themes. RESULTS: For some, pride was found in their professional identity and dedication to their work. Others took pride in specific achievements, such as juggling their own needs (e.g., health, private life) with those of the workplace, contributing to cohesion and collaboration, their ability to learn and adjust, in being a useful resource at work, and in their efforts towards developing the organization and workplace. IMPLICATIONS: The current findings shed light on what healthcare workers feel proud of achieving in their day-to-day work. Assessment of these factors provides insight on both positive and negative aspects of working clinically during a pandemic, and highlights specific targets for building sustainable and rewarding work environments for healthcare workers.

Exposure to traumatic events and use of over-the-counter analgesics in adolescents: cross-sectional findings from the Young-HUNT study.

OBJECTIVE: Frequent and increasing use of over-the-counter analgesics (OTCA) among adolescents is a public health concern. Prior research indicates that adolescents exposed to traumatic events may be at increased risk of suffering from headaches and musculoskeletal pain. In this study, we assessed the association between trauma exposure and use of OTCA for headaches and musculoskeletal pain. DESIGN: A cross-sectional population study among adolescents, self-reported data on trauma exposure, pain and use of OTCA. SETTING AND PARTICIPANTS: All 10 608 adolescents aged 13-19 years in a region of Norway were invited in this school-based survey, participation rate was 76%. OUTCOME MEASURE: Frequency of OTCA use for headache and musculoskeletal pain served as separate outcomes in ordinal logistic regression analyses. RESULTS: Trauma exposure was significantly and consistently related to higher frequency use of OTCA for headache and musculoskeletal pain, of which associations for bullying (OR 1.79, 95% CI 1.50 to 2.12, and OR 2.12, 95% CI 1.70 to 2.66), physical violence (OR 1.49, 95% CI 1.25 to 1.78 and OR 1.83, 95% CI 1.45 to 2.32) and sexual abuse (OR 1.83, 95% CI 1.55 to 2.18 and OR 1.53, 95% CI 1.18 to 1.90) were particularly strong. A dose-response relationship was found between interpersonal violence and OTCA use for headache (OR 1.46, 95% CI 1.29 to 1.66 for one type and OR 1.81, 95% CI 1.53 to 2.14 for two or more types) and musculoskeletal pain (OR 1.61, 95% CI 1.91 to 3.00 for one type and OR 2.39, 95% CI 1.91 to 3.00 for two or more types). The associations remained significant after adjustment for pain, although an attenuation in strength was observed. CONCLUSION: Trauma exposed adolescents use OTCA for headaches and musculoskeletal pain more frequently than those not exposed. The higher frequency of pain conditions among trauma exposed only partially explained their more frequent OTCA use, indicating an increased risk relating to features beyond frequency of pain.

Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study.

BACKGROUND: There are indications that use of menopausal hormone therapy (MHT) and oral contraceptives (OC) increases the risk of low back pain (LBP), with higher oestrogen levels involved in the underlying mechanisms. The purpose of the present study was to investigate associations between use of systemic MHT or OC and risk of chronic LBP in a large population-based data set. METHODS: Data were obtained from two surveys in the Trøndelag Health Study in Norway, HUNT2 (1995-1997) and HUNT3 (2006-2008). A cross-sectional study of association between use of systemic MHT and prevalence of chronic LBP comprised 12,974 women aged 40-69 years in HUNT2, with 4007 women reporting chronic LBP. A cohort study involving MHT comprised 6007 women without chronic LBP at baseline in HUNT2, and after 11 years 1245 women reported chronic LBP at follow-up in HUNT3. The cross-sectional study of association with use of OC included 23,593 women aged 20-69 years in HUNT2, with 6085 women reporting chronic LBP. The corresponding cohort study included 10,586 women without chronic LBP at baseline in HUNT2, of whom 2084 women reported chronic LBP in HUNT3. Risk of chronic LBP was examined in both study designs in generalised linear models with adjustment for potential confounders. RESULTS: In the cohort study, current users of systemic MHT at baseline showed a greater risk of chronic LBP (relative risk (RR) 1.30; 95% CI: 1.14-1.49; compared with never users). The risk increased according to duration of MHT use (P for linear trend = 0.003). Known users of systemic MHT based exclusively on oestrogen experienced the highest risk (RR 1.49; 95% CI: 1.16-1.91), but an increased risk was also seen among known users of oestrogen-progestin combination MHT (RR 1.35; 95% CI: 1.16-1.57). A slight increase in risk of chronic LBP was found in the cohort study among former users of OC (RR 1.17; 95% CI: 1.06-1.30; compared with never users). CONCLUSIONS: Long-lasting use of systemic MHT, in particular therapy based on oestrogen only, is associated with greater risk of chronic LBP. Having been a user of OC most likely entails a minor increase in risk.