The HUNT4 study: the validity of questionnaire-based diagnoses.

BACKGROUND: Questionnaire-based headache diagnoses should be validated against diagnoses made by the gold standard, which is personal interview by a headache expert. The diagnostic algorithm with the best diagnostic accuracy should be used when later analysing the data. METHODS: The Nord-Trøndelag Health Study (HUNT4) was performed between 2017 and 2019. Among HUNT4 participants, a total of 232 (19.3%) out of 1201 randomly invited were interviewed by a headache expert to assess the sensitivity, specificity and kappa value of the questionnaire-based headache diagnoses. RESULTS: The median interval between answering the headache questions and the validation interview was 60 days (95% CI 56-62 days). The best agreements were found for self-reported lifetime migraine (sensitivity of 59%, specificity of 99%, and a kappa statistic of 0.65, 95% CI 0.55-0.75), self-reported active migraine (sensitivity of 50%, specificity of 97%, and a kappa statistic of 0.55, 95% 0.39-0.71), liberal criteria of migraine (sensitivity of 64%, specificity of 93%, and a kappa statistic of 0.58, 95% CI 0.43-0.73) and ICDH3-based migraine ≥1 days/month (sensitivity of 50%, specificity of 94%, and a kappa statistic of 0.49, 95% CI 0.30-0.68). For headache suffering ≥1 days/month a sensitivity of 90%, specificity 80%, and a kappa statistic of 0.55, 95% CI 0.41-0-69 were found. For tension-type headache (TTH) ≥ 1 days/month the agreement was 0.33 (95% CI 0.17-0.49). CONCLUSION: The HUNT4 questionnaire is a valid tool for identifying persons with lifetime migraine, self-reported active migraine and active migraine applying liberal modified criteria. The agreement for TTH was fair.

The epidemiology of headache disorders: a face-to-face interview of participants in HUNT4.

BACKGROUND: The primary aim of this cross-sectional population-based study was to evaluate the 1-year prevalence of common headache disorders by a face-to-face interview. METHODS: The fourth wave of Nord-Trøndelag Health Survey (HUNT4) started in September 2017. The study was undertaken as part of a project mainly focusing on sleep disorders, where a total of 232 (19.3%) out of 1200 invited HUNT4 participants underwent a face-to-face headache interview. RESULTS: The mean age of the 232 participants was 58.4 years (range 22-89). There were 71.6% (95% CI 65.7-77.4) who reported headache during the last year, and 18.5% (95% CI 13.5-23.6) had suffered from headache in the same period. The 1-year prevalence of tension-type headache (TTH) was 43.1% (95% CI 36.7-49.5), of idiopathic stabbing headache 34.1% (27.9-40.2), and of definite migraine 18.1% (95% CI 13.1-23.1). A total of 7.6% (95% CI 4.0-10.7%) had migraine with coexisting TTH. Lifetime prevalence of migraine was 32.8% (95% CI 26.7-38.8). Headache yesterday was reported by 12.1% (95% CI 7.9-16.3), and 5.6% (95% CI 2.6-8.6) had headache during the interview. CONCLUSION: In this population-based cross-sectional headache study performed by a face-to-face interview, the 1-year prevalence of TTH was 43.1% and of idiopathic stabbing headache 34.1%. A total of 18.1% had active migraine (18.1%), whereas the lifetime prevalence of migraine was 32.8%.

The role of interleukin-1ß in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis.

OBJECTIVE: Interleukin-1ß (IL-1ß) is considered a pronociceptive cytokine, but its role in the generation of arthritic pain is unknown. The aim of this study was to investigate the role of IL-1ß in arthritic pain and to explore the antinociceptive potential of the IL-1 receptor type I (IL-1RI) antagonist anakinra. METHODS: Antigen-induced arthritis (AIA) was induced in rats. Expression of IL-1RI in the dorsal root ganglia (DRGs) was determined, and the effects of anakinra on inflammation, pain-related behavior, and receptor expression were assessed. In cultured DRG neurons, the effect of IL-1ß on the expression of the transient receptor potential vanilloid 1 (TRPV-1) ion channel was examined. Recordings of action potentials from joint nociceptors were made after intraarticular injection of IL-1ß into the rat knee joints. RESULTS: AIA generated pronounced and persistent mechanical and thermal hyperalgesia, and IL-1RI expression in the lumbar DRGs was significantly up-regulated. Treatment with anakinra did not significantly reduce the severity of arthritis or mechanical hyperalgesia, but did result in a pronounced reduction in thermal hyperalgesia. In cultured DRG neurons, IL-1ß up-regulated the expression of TRPV-1, a major transduction molecule involved in thermal hyperalgesia. During AIA, anakinra treatment down-regulated the expression of TRPV-1, consistent with the pronounced reduction in thermal hyperalgesia. IL-1ß increased the mechanosensitivity of C-fibers of the joint, but reduced the mechanosensitivity of Aδ-fibers, thus having opposite effects on these mechanonociceptive nerve fibers. CONCLUSION: In the context of arthritic knee pain, IL-1ß and IL-1 receptors appear to be involved in thermal, rather than mechanical, hyperalgesia. Therefore, neutralization of IL-1ß may be mainly antinociceptive in disease states characterized by thermal hyperalgesia, but not in disease states mainly characterized by mechanical hyperalgesia.

Molecular effects of interleukin-1ß on dorsal root ganglion neurons: prevention of ligand-induced internalization of the bradykinin 2 receptor and downregulation of G protein-coupled receptor kinase 2.

In dorsal root ganglion sections numerous small-to medium-sized neurons were found to exhibit extensive colocalization of the bradykinin receptor 2, the interleukin-1 receptor 1 and G protein-coupled receptor kinase 2. Application of bradykinin to cultured DRG neurons caused substantial internalization of the bradykinin 2 receptor which significantly reduced the responsiveness of DRG neurons to a second application of bradykinin. Such an internalization was not observed in DRG neurons which were exposed to long-term pretreatment with interleukin-1ß. The long-term incubation with interleukin-1ß on its own did neither change the proportion of neurons which expressed the bradykinin 2 receptor in the cytoplasma nor the proportion of neurons expressing the bradykinin 2 receptor in the membrane but it reduced the proportion of neurons expressing G protein-coupled receptor kinase 2, an enzyme which facilitates the internalization of G protein-coupled receptors. These results show that interleukin-1ß maintains the responsiveness of DRG neurons to bradykinin in the long-term range, and they suggest that the downregulation of G protein-coupled receptor kinase 2 could be a cellular mechanism involved in this interleukin-1ß effect.

Prevalence and associated factors of DSM-V insomnia in Norway: the Nord-Trøndelag Health Study (HUNT 3).

BACKGROUND: Many studies have assessed the prevalence of insomnia, but the influence of non-participants has largely been ignored. The objective of the present study was to estimate the prevalence and associated factors of insomnia in a large adult population using DSM-V (diagnostic and statistical manual of mental disorders, 5th ed.) criteria, also taking non-participants into account. METHODS: This cross-sectional study used data from a questionnaire in The Nord-Trøndelag Health Study (HUNT 3) performed in 2006-2008, and a subsequent non-participant study. The total adult population (n=93,860 aged > or =20 years) of Nord-Trøndelag County, Norway, was invited. Of these, 40,535 responded to the insomnia questionnaire. Among 42,024 eligible non-participants, 6918 (17%) responded to two insomnia questions. RESULTS: Insomnia was diagnosed by applying modified DSM-V criteria. The age-adjusted insomnia prevalence was estimated using the age distribution of all adult inhabitants of Nord-Trøndelag. Supplementary prevalence data were estimated by extrapolating data from the non-participant study. Additionally, the association between insomnia and self-reported health was estimated, adjusting for known confounders. The total age-adjusted prevalence of insomnia was 7.1% (95% confidence interval [CI], 6.9-7.4) (8.6% for women, 5.5% for men). Adjusting for non-participants, the prevalence estimate changed to 7.9% (95% CI, 7.3-8.6) (9.4% for women, 6.4% for men). Insomnia was more than eight times more likely (OR, 8.3; 95% CI, 6.2-11.1) among individuals with very poor versus very good self-reported health, adjusting for age, gender, employment status, chronic musculoskeletal complaints, anxiety and depression. CONCLUSIONS: The adjusted insomnia prevalence estimate in Nord-Trøndelag was 7.9%. Insomnia was strongly associated with poor self-reported health.