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Objectives: The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain., Methods: In total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test., Results: No significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia)., Conclusions: The selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background and aims Recovery in patients hospitalised with severe sciatica is unpredictable. Prognostic tools to aid clinicians in the early identification of patients at risk of developing chronic sciatic pain are warranted. Conditioned pain modulation (CPM) is a psychophysical measure of the endogenous pain modulatory pathways. Several studies have suggested CPM as a potentially important predictive biomarker for the development of chronic pain. The aim of the study was to determine whether CPM effect in patients still suffering from leg pain 6 weeks after hospital discharge for severe sciatica is associated with persistent leg pain at 12 months. A potential association would suggest that measuring CPM effect could be a valuable prognostic tool in the hospital management of sciatica. Methods A prospective cohort study in which CPM effect was measured 6 weeks after hospital discharge following an acute admission with sciatica as the main complaint. The impact of CPM effect on the outcome was analysed using logistic regression. The outcome measured was self-reported leg pain score of ≥1 in the past week on a 0-10 numeric rating scale (NRS) at 12 months post discharge. Results A total of 111 patients completed the entire study, 51 of whom received non-randomised surgical treatment. Crude and confounder adjusted analyses showed no significant association between CPM effect and leg-pain measured at 12 months, crude Odds Ratio 0.87, 95% CI 0.7-1.1, p = 0.23. Conclusions Our results suggest that CPM assessment has limited prognostic value for the long-term outcome in severe sciatica when measured 6 weeks after hospital discharge. Implications The present study adds important knowledge concerning the limited clinical use of late CPM testing in sciatica patients. The heterogeneity in patients, the wide range of treatments received and a generally favourable outcome are factors that may affect CPM's clinical value as a prognostic factor for severe sciatica.

Study Design: Prospective cohort study., Objective: To identify potential prognostic factors for persistent leg-pain at 12 months among patients hospitalized with acute severe sciatica., Summary of Background Data: The long-term outcome for patients admitted to hospital with sciatica is generally unfavorable. Results concerning prognostic factors for persistent sciatica are limited and conflicting., Methods: A total of 210 patients acutely admitted to hospital for either surgical or nonsurgical treatment of sciatica were consecutively recruited and received a thorough clinical and radiographic examination in addition to responding to a comprehensive questionnaire. Follow-up assessments were done at 6 weeks, 6 months, and 12 months. Potential prognostic factors were measured at baseline and at 6 weeks. The impact of these factors on leg-pain was analyzed by multiple linear regression modeling., Results: A total of 151 patients completed the entire study, 93 receiving nonrandomized surgical treatment. The final multivariate models showed that the following factors were significantly associated with leg-pain at 12 months: high psychosocial risk according to the Örebro Musculosceletal Pain Questionnaire (unstandardized beta coefficient 1.55, 95% confidence interval [CI] 0.72-2.38, P < 0.001), not receiving surgical treatment (1.11, 95% CI 0.29-1.93, P = 0.01), not actively employed upon admission (1.47, 95% CI 0.63-2.31, P < 0.01), and self-reported leg-pain recorded 6 weeks posthospital admission (0.49, 95% CI 0.34-0.63, P < 0.001). Interaction analysis showed that the Örebro Musculosceletal Pain Questionnaire had significant prognostic value only on the nonsurgically treated patients (3.26, 95% CI 1.89-4.63, P < 0.001)., Conclusion: The results suggest that a psychosocial screening tool and the implementation of a 6-week postadmission follow-up has prognostic value in the hospital management of severe sciatica., Level of Evidence: 2.

Background: Although an inverse relationship between pain sensitivity and hypertension has been described, it is still unknown whether hypertension may protect against chronic musculoskeletal complaints (MSCs). The aim of this study was to evaluate the relationship between blood pressure (BP) and prevalence of chronic MSCs at various anatomical sites., Methods: Two consecutive public health studies within the county of Nord-Trøndelag, Norway, were conducted between January 5, 1984, and February 15, 1986 (Nord-Trøndelag Health Study [HUNT] 1), and from August 1995 to June 1997 (HUNT-2). Among 46 901 adults who participated in both surveys, 24 127 (51.4%) in HUNT-2 who reported MSCs continuously for at least 3 months during the past year were defined as having chronic MSCs. The prevalence of chronic MSCs was estimated using multiple logistic regression, with odds ratio and 95% confidence interval as measures of association with systolic and diastolic BP., Results: A high systolic and diastolic BP was associated with a 10% to 60% lower prevalence of chronic MSCs, and there was a strong linear trend (P<.001) of decreasing prevalence of chronic MSCs with increasing BP values. The findings were remarkably consistent at all anatomical sites, for both sexes, across all age groups, and for systolic and diastolic BP measured in HUNT-1 and HUNT-2., Conclusions: Individuals with a high BP had a lower prevalence of chronic MSCs than individuals with a normal BP. One possible explanation may be the phenomenon of hypertension-associated hypalgesia, due to an interaction between the cardiovascular and pain regulatory systems. The effect of antihypertensive medication on this interaction should be evaluated in further studies.

Background and aims: Recovery in patients hospitalised with severe sciatica is unpredictable. Prognostic tools to aid clinicians in the early identification of patients at risk of developing chronic sciatic pain are warranted. Conditioned pain modulation (CPM) is a psychophysical measure of the endogenous pain modulatory pathways. Several studies have suggested CPM as a potentially important predictive biomarker for the development of chronic pain. The aim of the study was to determine whether CPM effect in patients still suffering from leg pain 6 weeks after hospital discharge for severe sciatica is associated with persistent leg pain at 12 months. A potential association would suggest that measuring CPM effect could be a valuable prognostic tool in the hospital management of sciatica. Methods: A prospective cohort study in which CPM effect was measured 6 weeks after hospital discharge following an acute admission with sciatica as the main complaint. The impact of CPM effect on the outcome was analysed using logistic regression. The outcome measured was self-reported leg pain score of ≥1 in the past week on a 0–10 numeric rating scale (NRS) at 12 months post discharge. Results: A total of 111 patients completed the entire study, 51 of whom received non-randomised surgical treatment. Crude and confounder adjusted analyses showed no significant association between CPM effect and leg-pain measured at 12 months, crude Odds Ratio 0.87, 95% CI 0.7–1.1, p = 0.23. Conclusions: Our results suggest that CPM assessment has limited prognostic value for the long-term outcome in severe sciatica when measured 6 weeks after hospital discharge. Implications: The present study adds important knowledge concerning the limited clinical use of late CPM testing in sciatica patients. The heterogeneity in patients, the wide range of treatments received and a generally favourable outcome are factors that may affect CPM's clinical value as a prognostic factor for severe sciatica. [ABSTRACT FROM AUTHOR]

Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10−5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders. [ABSTRACT FROM AUTHOR]

Background: Physical activity in leisure time seems to reduce the risk of low back pain, but it is not known whether occupational activity, as recorded in a representative working population, produces a higher or lower risk. Objective: To study associations between physical activity level at work and risk of chronic low back pain. Methods: Associations were examined in a Norwegian prospective study using data from the HUNT2 and HUNT3 surveys carried out in the whole county of Nord-Trøndelag. Participants were 7580 women and 7335 men who supplied information about physical activity level at work. Levels considered were sedentary work, work involving walking but no heavy lifting, work involving walking and heavy lifting, and particularly strenuous physical work. Nobody in the cohort was affected by chronic low back pain at baseline. After 11 years, participants reported whether they suffered from chronic low back pain. Generalized linear modelling with adjustment for potential confounders was applied to assess associations with risk factors. Results: In age-adjusted analyses both women and men showed statistically significant associations between physical activity at work and risk of chronic low back pain, suggesting positive relationships. For particularly strenuous physical work the relative risk of chronic low back pain was 1.30 (95% CI: 1.00–1.71) in women and 1.36 (95% CI 1.17–1.59) in men, compared to sedentary work. Women still showed a general association with activity level after adjustment for education, leisure time physical activity, BMI, smoking and occupational category. In men, the higher risk was only maintained for particularly strenuous work. Conclusion: In this cohort, women had a higher risk of chronic low back pain with work involving walking and heavy lifting or particularly strenuous work, compared to sedentary work. Men participating in particularly strenuous work also experienced a higher risk of chronic low back pain. [ABSTRACT FROM AUTHOR]

Purpose: Standard surgical treatment for symptomatic cervical disc disease has been discectomy and fusion, but the use of arthroplasty, designed to preserve motion, has increased, and most studies report clinical outcome in its favor. Few of these trials, however, blinded the patients. We, therefore, conducted the Norwegian Cervical Arthroplasty Trial, and present 2-year clinical outcome after arthroplasty or fusion.Methods: This multicenter trial included 136 patients with single-level cervical disc disease. The patients were randomized to arthroplasty or fusion, and blinded to the treatment modality. The surgical team was blinded to randomization until nerve root decompression was completed. Primary outcome was the self-rated Neck Disability Index. Secondary outcomes were the numeric rating scale for pain and quality of life questionnaires Short Form-36 and EuroQol-5Dimension-3 Level.Results: There was a significant improvement in the primary and all secondary outcomes from baseline to 2-year follow-up for both arthroplasty and fusion (P < 0.001), and no observed significant between-group differences at any follow-up times. However, linear mixed model analyses, correcting for baseline values, dropouts and missing data, revealed a difference in Neck Disability Index (P = 0.049), and arm pain (P = 0.027) in favor of fusion at 2 years. The duration of surgery was longer (P < 0.001), and the frequency of reoperations higher (P = 0.029) with arthroplasty.Conclusion: The present study showed excellent clinical results and no significant difference between treatments at any scheduled follow-up. However, the rate of index level reoperations was higher and the duration of surgery longer with arthroplasty.Trial Registration: http://www.clinicaltrials.gov NCT 00735176.19. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional studies suggest associations between abnormal lipid levels and prevalence of low back pain (LBP), but it is not known if there is any causal relationship. Objective: The objective was to determine, in a population-based prospective cohort study, whether there is any relation between levels of total cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides and the probability of experiencing subsequent chronic (LBP), both among individuals with and without LBP at baseline. Methods: Information was collected in the community-based HUNT 2 (1995–1997) and HUNT 3 (2006–2008) surveys of an entire Norwegian county. Participants were 10,151 women and 8731 men aged 30–69 years, not affected by chronic LBP at baseline, and 3902 women and 2666 men with LBP at baseline. Eleven years later the participants indicated whether they currently suffered from chronic LBP. Results: Among women without LBP at baseline, HDL cholesterol levels were inversely associated and triglyceride levels positively associated with the risk of chronic LBP at end of follow-up in analyses adjusted for age only. Adjustment for the baseline factors education, work status, physical activity, smoking, blood pressure and in particular BMI largely removed these associations (RR: 0.96, 95% CI: 0.85–1.07 per mmol/l of HDL cholesterol; RR: 1.16, 95% CI: 0.94–1.42 per unit of lg(triglycerides)). Total cholesterol levels showed no associations. In women with LBP at baseline and men without LBP at baseline weaker relationships were observed. In men with LBP at baseline, an inverse association with HDL cholesterol remained after complete adjustment (RR: 0.83, 95% CI: 0.72–0.95 per mmol/l). Conclusion: Crude associations between lipid levels and risk of subsequent LBP in individuals without current LBP are mainly caused by confounding with body mass. However, an association with low HDL levels may still remain in men who are already affected and possibly experience a higher pain intensity. [ABSTRACT FROM AUTHOR]

A slight predominance of cluster pain on the right side has been reported in several studies. The aim of this large retrospective Nordic multicenter study was to estimate the prevalence of right- and left-sided pain in cluster headache (CH) patients with side-locked pain, the prevalence of side shifts in episodic and chronic CH patients, and the occurrence of cranial autonomic symptoms related to pain side. Among 383 cluster patients, 55 (14%) had experienced pain side shift. Of the remaining 328 individuals without side shift, there was no significant difference between the occurrence of right-sided and left-sided pain (54 vs. 46%). The prevalence of side shift was similar for episodic and chronic CH and the occurrence of cranial autonomic symptoms was not influenced by the pain side. In conclusion, previous reports of a side difference in location of cluster pain could not be confirmed in this large Nordic sample. [ABSTRACT FROM AUTHOR]

Objectives.—To examine the relationship between migraine and nonmigrainous headache and asthma, hay fever, and chronic bronchitis in a large cross-sectional population-based study. Background.—Associations between prevalence of migraine and asthma or allergy have been demonstrated in clinic-based and epidemiologic studies whereas studies on chronic bronchitis are scarce. Methods.—A total of 51,383 subjects completed a headache questionnaire and constituted the “Head-HUNT” Study. Of these 50,401 (98.1%) answered the questions about asthma and chronic bronchitis, and 47,029 (91.5%) answered the question about hay fever. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CI). Results.—Both migraine and nonmigrainous headache were approximately 1.5 times more likely among those with current asthma, asthma related symptoms, hay fever, and chronic bronchitis than those without. The association increased with increasing headache frequency. Conclusions.—This large questionnaire-based study confirms that migraine and other headaches are associated with respiratory and allergic disorders. The magnitude of the association between headache and asthma, hay fever, and chronic bronchitis tended to be in the same order. Headache frequency seems to have a greater impact on the association with respiratory or allergic conditions than headache diagnoses. Whether it is a causal relationship is uncertain, but the results underline the importance of considering comorbid disorders among patients with frequent headache. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives. To assess the prevalence of chronic musculoskeletal complaints (MSCs) in a large adult population, and to determine any changes in prevalence during an 11-year period. Methods. This study involved two large cross-sectional surveys (Helseundersøkelsen i Nord-Trøndelag [HUNT] 2 and 3) of inhabitants in Nord-Trøndelag county aged ≥20 years performed in 1995-97 (N = 92,936) and 2006-08 (N = 94,194). Attendance rates were 70 and 42%, respectively. Respondents with chronic MSCs were identified through the screening question 'Have you during the last year continuously for at least 3 months had pain and/or stiffness in muscles and joints?' The reliability of the screening question was evaluated in a random sample of participants (N = 563). Results. The reliability of the screening question was good (kappa value 0.63, 95% confidence interval [CI] 0.53-0.73). In HUNT 3, 48% had chronic MSCs and 20% had chronic widespread MSCs. The age-adjusted prevalence of chronic MSCs was higher ( P < 0.001) in HUNT 3 (47.9%, 95% CI 47.6-48.2) compared with HUNT 2 (44.8%, 95% CI 44.5-45.2), evident for both genders, and most prominent in the age group 20-29 years. Chronic widespread MSCs were more common in HUNT 3 than in HUNT 2 among women (28.2 vs 26.0%, P < 0.001). Increased prevalence during the 11-year period was also found in supplementary analyses evaluating the influence of differences in participation rate. Conclusions. The prevalence of chronic MSCs and chronic widespread MSCs is high. The prevalence of chronic MSCs increased during the 11-year period. A nonresponse bias interfering with the comparisons over time could not completely be ruled out. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to determine the prevalence of self-reported chronic idiopathic pain among adolescents in relation to age and gender, and to explore how pain interferes with daily activities. The study was performed in Nord-Trøndelag County, Norway in 2006–2008. All adolescents were invited to participate; the response rate was 78%. Participants completed a comprehensive questionnaire, including questions about pain and interference with everyday life. Chronic idiopathic pain was defined as pain at least once a week during the last 3months, not related to any known disease or injury. The final study population, with complete pain questionnaires, consisted of 7373 adolescents aged 13–18years. Chronic pain was reported by 44.4% of the participants, and 25.5% reported pain in at least 2 locations. Chronic idiopathic musculoskeletal pain was most prevalent (33.4%), and the neck/shoulder was most commonly affected. Musculoskeletal pain in 3 or more locations was reported by 8.5%. Pain almost daily was reported by 10.2%. More girls than boys reported pain. In girls, the prevalence of pain increased with age. A high number of pain-associated disabilities were reported, and 58.5% described difficulties doing daily activities in leisure time. Subjective disabilities were higher in girls, and increased with the frequency of pain and the number of pain locations, as shown by high disability in adolescents with musculoskeletal pain in 3 or more locations. Chronic idiopathic pain, especially multisite pain, is common among adolescents, and those suffering from it report a major impact on several areas of daily living. [Copyright &y& Elsevier]