Poorer sleep health is associated with altered brain activation during cognitive control processing in healthy adults.

This study investigated how proactive and reactive cognitive control processing in the brain was associated with habitual sleep health. BOLD fMRI data were acquired from 81 healthy adults with normal sleep (41 females, age 20.96-39.58 years) during a test of cognitive control (Not-X-CPT). Sleep health was assessed in the week before MRI scanning, using both objective (actigraphy) and self-report measures. Multiple measures indicating poorer sleep health-including later/more variable sleep timing, later chronotype preference, more insomnia symptoms, and lower sleep efficiency-were associated with stronger and more widespread BOLD activations in fronto-parietal and subcortical brain regions during cognitive control processing (adjusted for age, sex, education, and fMRI task performance). Most associations were found for reactive cognitive control activation, indicating that poorer sleep health is linked to a "hyper-reactive" brain state. Analysis of time-on-task effects showed that, with longer time on task, poorer sleep health was predominantly associated with increased proactive cognitive control activation, indicating recruitment of additional neural resources over time. Finally, shorter objective sleep duration was associated with lower BOLD activation with time on task and poorer task performance. In conclusion, even in "normal sleepers," relatively poorer sleep health is associated with altered cognitive control processing, possibly reflecting compensatory mechanisms and/or inefficient neural processing.

Effects of insufficient sleep on sensorimotor processing in migraine: A randomised, blinded crossover study of event related beta oscillations.

BACKGROUND: Migraine has a largely unexplained connection with sleep and is possibly related to a dysfunction of thalamocortical systems and cortical inhibition. In this study we investigate the effect of insufficient sleep on cortical sensorimotor processing in migraine. METHODS: We recorded electroencephalography during a sensorimotor task from 46 interictal migraineurs and 28 controls after two nights of eight-hour habitual sleep and after two nights of four-hour restricted sleep. We compared changes in beta oscillations of the sensorimotor cortex after the two sleep conditions between migraineurs, controls and subgroups differentiating migraine subjects usually having attacks starting during sleep and not during sleep. We included preictal and postictal recordings in a secondary analysis of temporal changes in relation to attacks. RESULTS: Interictally, we discovered lower beta synchronisation after sleep restriction in sleep related migraine compared to non-sleep related migraine (p=0.006) and controls (p=0.01). No differences were seen between controls and the total migraine group in the interictal phase. After migraine attacks, we observed lower beta synchronisation (p<0.001) and higher beta desynchronisation (p=0.002) after sleep restriction closer to the end of the attack compared to later after the attack. CONCLUSION: The subgroup with sleep related migraine had lower sensorimotor beta synchronisation after sleep restriction, possibly related to dysfunctional GABAergic inhibitory systems. Sufficient sleep during or immediately after migraine attacks may be of importance for maintaining normal cortical excitability.

Insufficient sleep may alter cortical excitability near the migraine attack: A blinded TMS crossover study.

BACKGROUND: Migraine is a brain disorder with a multifaceted and unexplained association to sleep. Brain excitability likely changes periodically throughout the migraine cycle. In this study we examine the effect of insufficient sleep on neuronal excitability during the course of the migraine cycle. METHODS: We examined 54 migraine patients after two nights of eight-hour habitual sleep and two nights of four-hour restricted sleep in a randomised, blinded crossover study. We performed transcranial magnetic stimulation and measured cortical silent period, short- and long-interval intracortical inhibition, intracortical facilitation and short-latency afferent inhibition. We analysed how responses changed before and after attacks with linear mixed models. RESULTS: Short- interval intracortical inhibition was more reduced after sleep restriction compared to habitual sleep the shorter the time that had elapsed since the attack (p = 0.041), and specifically in the postictal phase (p = 0.013). Long-interval intracortical inhibition was more increased after sleep restriction with time closer before the attack (p = 0.006), and specifically in the preictal phase (p = 0.034). Short-latency afferent inhibition was more decreased after sleep restriction with time closer to the start of the attack (p = 0.026). CONCLUSION: Insufficient sleep in the period leading up to a migraine attack may cause dysfunction in cortical GABAergic inhibition. The results also suggest that migraine patients may have increased need for sufficient sleep during a migraine attack to maintain normal neurological function after the attack.

Which combined nerve conduction study scores are best suited for polyneuropathy in diabetic patients?

INTRODUCTION/AIMS: Nerve conduction studies (NCS) are widely used in diagnosing diabetic polyneuropathy. Combining the Z scores of several measures (Z-compounds) may improve diagnostics by grading abnormality. We aimed to determine which combination of nerves and measures is best suited for studies of diabetic polyneuropathy. METHODS: Sixty-eight patients with type 1 diabetes and 35 controls were included in this study. NCS measurements were taken from commonly investigated nerves in one arm and both legs. Different Z-compounds were calculated and compared with reference material to assess abnormality. A sensitivity proxy, the accuracy index (AI), and Cohen's d were calculated. RESULTS: Z-compounds with the highest AI consisted of the tibial and peroneal motor, and the sural, superficial peroneal, and tibial medial plantar sensory nerves in one or two legs. All Z-compounds were able to discriminate between diabetic subjects and nondiabetic controls (mean Cohen's d = 1.42 [range, 1.03-1.63]). The association between AI and number of measures was best explained logarithmically (R2  = 0.401), with diminishing returns above approximately 14 or 15 measures. F-wave inclusion may increase the AI of the Z compounds. Although often clinically useful among the non-elderly, the additional inclusion of medial plantar NCS into Z-compounds in general did not improve AI. DISCUSSION: Performing unilateral NCS in several motor and sensory lower extremity nerves is suited for the evaluation of polyneuropathy in diabetic patients. The use of Z-compounds may improve diagnostic accuracy in diabetic polyneuropathy and may be particularly useful for follow-up research studies as single summary measures of NCS abnormality development over time.

Pain thresholds and suprathreshold pain after sleep restriction in migraine - A blinded crossover study.

OBJECTIVE: There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls. METHODS: Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep. RESULTS: The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group. CONCLUSION: This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.

Contact-free radar recordings of body movement can reflect ultradian dynamics of sleep.

This work aimed to evaluate if a contact-free radar sensor can be used to observe ultradian patterns in sleep physiology, by way of a data processing tool known as Locomotor Inactivity During Sleep (LIDS). LIDS was designed as a simple transformation of actigraphy recordings of wrist movement, meant to emphasise and enhance the contrast between movement and non-movement and to reveal patterns of low residual activity during sleep that correlate with ultradian REM/NREM cycles. We adapted the LIDS transformation for a radar that detects body movements without direct contact with the subject and applied it to a dataset of simultaneous recordings with polysomnography, actigraphy, and radar from healthy young adults (n = 12, four nights of polysomnography per participant). Radar and actigraphy-derived LIDS signals were highly correlated with each other (r > 0.84), and the LIDS signals were highly correlated with reduced-resolution polysomnographic hypnograms (rradars >0.80, ractigraph >0.76). Single-harmonic cosine models were fitted to LIDS signals and hypnograms; significant differences were not found between their amplitude, period, and phase parameters. Mixed model analysis revealed similar slopes of decline per cycle for radar-LIDS, actigraphy-LIDS, and hypnograms. Our results indicate that the LIDS technique can be adapted to work with contact-free radar measurements of body movement; it may also be generalisable to data from other body movement sensors. This novel metric could aid in improving sleep monitoring in clinical and real-life settings, by providing a simple and transparent way to study ultradian dynamics of sleep using nothing more than easily obtainable movement data.

Validation of questionnaires for restless legs syndrome in the general population: the Trøndelag Health Study (HUNT).

Questionnaires for restless legs syndrome have rarely been validated against face-to-face interviews in the general population. We aimed to validate the modified Norwegian, seven-item Cambridge-Hopkins restless legs syndrome questionnaire and a single diagnostic question for restless legs syndrome. We also aimed to stratify validity at 65 years of age. Among a random sample of 1,201 participants from the fourth wave of the Trøndelag Health Study, 232 (19%) agreed to participate, out of whom 221 had complete data for analyses. Participants completed the questionnaires for restless legs syndrome immediately before attending a face-to-face interview using the latest diagnostic criteria. We calculated sensitivity, specificity, and Cohen's kappa statistic (κ) of questionnaire- versus interview-based diagnoses. We found acceptable validity of the seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome (κ = 0.37, 95% confidence interval [CI] 0.23-0.51) and good validity of the single diagnostic question (κ = 0.47, 95% CI 0.35-0.58). We also found good validity through the combination of modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome items 2 and 5, while item 1 or 2 alone showed only acceptable validity. The single diagnostic question was significantly more valid among those aged <65 years (κ = 0.60 versus κ = 0.26). Both single- and two-item questionnaire-based diagnoses overestimated interview-based restless legs syndrome prevalence. The seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome will be useful for epidemiological studies although low sensitivity may cause underestimation of true restless legs syndrome prevalence in the general population, especially among elderly. Brief questionnaire-based diagnoses of up to three items seem best utilised as an initial screen. Future studies should identify brief and even more valid questionnaire-based diagnoses for restless legs syndrome in order to estimate prevalence accurately in large epidemiological studies.

Daily associations between sleep and pain in patients with chronic musculoskeletal pain.

Patients with chronic pain commonly report sleep problems, and the evidence for a relationship between sleep disturbance and pain seems robust. The day-to-day associations between these constructs are less well studied, particularly with objective sleep measures such as actigraphy. Moreover, the concurrent presence of negative affective symptoms, as well as seasonality effects at extreme latitudes may complicate it further. Here, we studied 56 patients with chronic primary musculoskeletal pain conditions, contributing data in two separate 7-day data-collection periods during the summer and winter, respectively. The effect of self-reported sleep quality, and actigraphy measured sleep duration, efficiency and timing on next-day pain, as well as the effect of pain on the same sleep indices were estimated by generalised linear mixed regression models. The models were additionally adjusted for age, sex, education, data collection period, weekend, season and mental distress, with the latter two also specified as moderators. We observed a significant effect of pain as a predictor of next-night sleep quality (p = .003) and marginally of next-night sleep duration (p = .079). Conversely, sleep quality tentatively predicted next-day pain (p = .063). No other day-to-day associations were present. Mental distress was the strongest predictor of pain, but it did not modify the sleep-pain associations, nor did season. In conclusion pain, sleep quality and mental distress are closely related, underscoring the importance of encompassing this complexity in assessment and treatment of patients with chronic pain.

Validation of insomnia questionnaires in the general population: The Nord-Trøndelag Health Study (HUNT).

The primary aim was to validate questionnaire-based insomnia diagnoses from a modified Karolinska Sleep Questionnaire (KSQ) and the Insomnia Severity Index (ISI), by age category (< or >65 years), against a semi-structured face-to-face interview. Secondary aims were to split validity by diagnostic certainty of the interview and to compare prevalence estimates of questionnaire- and interview-based diagnoses. A total of 232 out of 1,200 invited (19.3%) from the fourth Nord-Trøndelag Health Study (HUNT4) completed questionnaires, including the KSQ and ISI, shortly before attending a face-to-face diagnostic interview for insomnia based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Both a tentative (DSM-5 criteria A-E) and a definite (criteria A-H) interview diagnosis was evaluated. Cohen's kappa statistic quantified questionnaire validity. In all, 33% (95% confidence interval 27-39%) of participants had definite insomnia: 40% of women and 21% of men. The ISI (cut-off 12) and several KSQ-based diagnoses showed very good validity (κ ≤0.74) against the tentative, versus good validity (κ ≤0.61) against the definite interview diagnosis. Short questionnaires, requiring a daytime symptom at least three times a week, may underestimate insomnia prevalence. Validity was consistently higher for persons aged below versus above 65 years (definite insomnia: κ ≤0.64 vs. κ ≤0.56). Our results have implications for epidemiological population-based studies utilising insomnia questionnaires.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Work-Related Mental Fatigue, Physical Activity and Risk of Insomnia Symptoms: Longitudinal Data from the Norwegian HUNT Study.

OBJECTIVE/BACKGROUND: To examine the prospective association between work-related mental fatigue and risk of insomnia symptoms, and if leisure time physical activity modifies this association. PARTICIPANTS: A total of 8,464 women and 7,480 men who participated in two consecutive surveys of the Norwegian HUNT study. METHODS: The study comprises longitudinal data on persons who were vocationally active and without insomnia symptoms at baseline in 1995-1997. We used a modified Poisson regression model to calculate adjusted risk ratios (RRs) with a 95% confidence interval (CI) for insomnia symptoms at follow-up in 2006-2008 associated with work-related mental fatigue and leisure time physical activity at baseline. RESULTS: Women and men who always experienced mental fatigue after a workday had RRs of insomnia symptoms of 2.55 (95% CI 1.91-3.40) and 2.61 (95% CI 1.80-3.78), respectively, compared to workers who never or seldom had this experience. There was no strong modifying effect of leisure time physical activity on this association, but workers who always experienced mental fatigue had a RR of insomnia symptoms of 3.17 (95% CI 2.28-4.40) if they reported low physical activity and a RR of 2.52 (95% 1.89-3.39) if they reported high physical activity. CONCLUSION: This study shows that work-related mental fatigue, caused by high cognitive workload, is a strong risk factor for insomnia symptoms. There was no clear modifying effect of leisure time physical activity but workers who experienced excessive work-related fatigue accompanied by low physical activity had the highest risk of insomnia symptoms.

Cognitive performance in DSWPD patients upon awakening from habitual sleep compared with forced conventional sleep.

Difficult early morning awakening is one of the defining symptoms of delayed sleep-wake phase disorder. It is accompanied by low cognitive arousal and drowsiness resulting in difficulty concentrating and focusing attention upon awakening. We designed the current study to quantitate cognitive performance (i.e. omissions, commissions, reaction time [average and variability]) and cognitive domains (i.e. focused attention, sustained attention, impulsivity and vigilance) with Conners' Continuous Performance Test II during both habitual and conventional (00:00-07:00 hr) sleep-wake schedule in young adult patients with delayed sleep-wake phase disorder (n = 20, mean age = 24.8 years, SD = 3.0) and controls (n = 16, mean age = 24.4 years, SD = 3.4). Conners' Continuous Performance Test II was administered after awakening and in the afternoon during both habitual and conventional conditions. In-laboratory polysomnography was performed for 2 nights. We assessed sleep, tiredness, chronotype and depression using questionnaires. Saliva was sampled for dim light melatonin onset measurements. Repeated-measures ANOVAs were applied for the Conners' Continuous Performance Test II measures with group (patient/control), time (afternoon/morning) and condition (habitual/conventional schedule) as fixed factors. Patients with delayed sleep-wake phase disorder had reduced reaction times, especially in the morning, greater response speed variability, and made more omission and commission errors compared with controls. Patients with delayed sleep-wake phase disorder also had reduced focused attention, especially upon forced early awakening. The short total sleep time of patients with delayed sleep-wake phase disorder could not statistically explain this outcome. In conclusion, we observed a state-dependent reduced ability to focus attention upon early morning awakening in patients with delayed sleep-wake phase disorder. Patients also had more omissions, longer reaction time and increased RT variability after habitual sleep, suggesting a possible small cognitive trait dysfunction in delayed sleep-wake phase disorder.

Epileptological aspects of juvenile neuronal ceroid lipofuscinosis (CLN3 disease) through the lifespan.

PURPOSE: Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) is the most common neurodegenerative disorder in childhood with survival until young adult age. Visual loss is followed by epilepsy, cognitive, neuropsychiatric, and motor symptoms. We have studied the evolution of electroencephalographic (EEG) and seizure characteristics. METHODS: Twenty-four patients were recruited via the Norwegian CLN3 disease parent association. Parents were interviewed. Medical records and EEG reports/recordings were collected. Electroencephalographic elements were classified according to Standardized computer-based organized reporting of EEG (SCORE). The evolution of EEG features along with seizure types was assessed by testing the difference in proportions with standardized normal deviate comparing findings below and above 15 years of age. RESULTS: Mean age at study or death (n = 12) was 21.2 (10-39) years. Twenty-two patients had experienced seizures; the first was usually bilateral tonic-clonic (TC). Later, focal motor seizures frequently occurred, often with increasing multifocal and polymorphic features. Paroxysmal nonepileptic motor and autonomous symptoms were also suspected in several patients. Distinct myoclonic seizures were uncommon. In four patients, we identified episodes of bradycardia/sinus arrest. Electroencephalography showed progressive slowing of the background activity (p = 0.029). Focal epileptiform discharges were rare and mainly seen at age <10. Combined multifocal and bilateral epileptiform discharges increased in adolescence (p = 0.002). CONCLUSION: Seizure and EEG characteristics change with time in CLN3 disease. Tonic-clonic seizures are common at onset, and multifocal motor seizures increase with age. In contrast, focal epileptiform abnormalities are more common in childhood, compared to later multifocal and bilateral discharges. This seizure disorder belongs to the combined generalized and focal epilepsies. Paucity of myoclonic seizures does not warrant classification as a classic progressive myoclonic epilepsy. When attacks with only behavior arrest occur, cardiac conduction abnormalities should be considered.

Fluctuations of sensorimotor processing in migraine: a controlled longitudinal study of beta event related desynchronization.

BACKGROUND: The migraine brain seems to undergo cyclic fluctuations of sensory processing. For instance, during the preictal phase, migraineurs experience symptoms and signs of altered pain perception as well as other well-known premonitory CNS-symptoms. In the present study we measured EEG-activation to non-painful motor and sensorimotor tasks in the different phases of the migraine cycle by longitudinal measurements of beta event related desynchronization (beta-ERD). METHODS: We recorded electroencephalography (EEG) of 41 migraine patients and 31 healthy controls. Each subject underwent three EEG recordings on three different days with classification of each EEG recording according to the actual migraine phase. During each recording, subjects performed one motor and one sensorimotor task with the flexion-extension movement of the right wrist. RESULTS: Migraine patients had significantly increased beta-ERD and higher baseline beta power at the contralateral C3 electrode overlying the primary sensorimotor cortex in the preictal phase compared to the interictal phase. We found no significant differences in beta-ERD or baseline beta power between interictal migraineurs and controls. CONCLUSION: Increased preictal baseline beta activity may reflect a decrease in pre-activation in the sensorimotor cortex. Altered pre-activation may lead to changes in thresholds for inhibitory responses and increased beta-ERD response, possibly reflecting a generally increased preictal cortical responsivity in migraine. Cyclic fluctuations in the activity of second- and third-order afferent somatosensory neurons, and their associated cortical and/or thalamic interneurons, may accordingly also be a central part of the migraine pathophysiology.

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 crossover design for migraine preventives: an analyses of four randomized placebo-controlled trials.

AIMS: To evaluate the crossover design in migraine preventive treatment trials by assessing dropout rate, and potential period and carryover effect in four placebo-controlled randomized controlled trials (RCTs). METHODS: In order to increase statistical power, the study combined data from four different RCTs performed from 1998 to 2015 at St. Olavs Hospital, Norway. Among 264 randomized patients, 120 received placebo treatment before and 144 after active treatment. RESULTS: Only 26 (10%) dropped out during the follow-up period of 30-48 weeks, the majority (n = 19) in the first 12 weeks. No period effect was found, since the treatment sequence did not influence the responder rate after placebo treatment, being respectively for migraine 30.5% vs. 27.4% (p = 0.59) and for headache 25.0% vs. 24.8% (p = 0.97, Chi-square test) when placebo occurred early or late. Furthermore, no carryover effect was identified, since the treatment sequence did not influence the treatment effect (difference between placebo and active treatment). There was no significant difference between those who received active treatment first and those who received placebo first with respect to change in number of days per 4 week of headache (- 0.9 vs. -1.3, p = 0.46) and migraine (- 1.2 vs. -0.9, p = 0.35, Student's t-test). CONCLUSIONS: Summary data from four crossover trials evaluating preventive treatment in adult migraine showed that few dropped out after the first period. No period or carryover effect was found. RCT studies with crossover design can be recommended as an efficient and cost-saving way to evaluate potential new preventive medicines for migraine in adults.

Alterations in post-movement beta event related synchronization throughout the migraine cycle: A controlled, longitudinal study.

Background The migraine brain is believed to have altered cortical excitability compared to controls and between migraine cycle phases. Our aim was to evaluate post-activation excitability through post-movement beta event related synchronization (PMBS) in sensorimotor cortices with and without sensory discrimination. Subjects and methods We recorded EEG of 41 migraine patients and 31 healthy controls on three different days with classification of days in relation to migraine phases. During each recording, subjects performed one motor and one sensorimotor task with the right wrist. Controls and migraine patients in the interictal phase were compared with repeated measures (R-) ANOVA and two sample Student's t-test. Migraine phases were compared to the interictal phase with R-ANOVA and paired Student's t-test. Results The difference between PMBS at the contralateral and ipsilateral sensorimotor cortex was altered throughout the migraine cycle. Compared to the interictal phase, we found decreased PMBS at the ipsilateral sensorimotor cortex in the ictal phase and increased PMBS in the preictal phase. Lower ictal PMBS was found in bilateral sensorimotor cortices in patients with right side headache predominance. Conclusion The cyclic changes of PMBS in migraine patients may indicate that a dysfunction in deactivation and interhemispheric inhibition of the sensorimotor cortex is involved in the migraine attack cascade.

Do physical activity and body mass index modify the association between chronic musculoskeletal pain and insomnia? Longitudinal data from the HUNT study, Norway.

We investigated the prospective association between chronic musculoskeletal pain and risk of insomnia, and if leisure-time physical activity and body mass index modify this association. The study comprised historical data on 11 909 women and 9938 men in the Norwegian HUNT study without sleep problems at baseline in 1995-97 and followed-up for insomnia in 2006-08. Poisson regression was used to estimate adjusted risk ratios (RRs) with 95% confidence intervals (CIs). Compared to pain-free participants, any chronic pain was associated with a RR of insomnia of 2.27 (95% CI: 1.93, 2.66) in women and 1.58 (95% CI: 1.28, 1.95) in men, whereas reporting ≥5 chronic pain sites gave RRs of 3.20 (95% CI: 2.60, 3.95) and 2.40 (95% CI: 1.76, 3.27), respectively. Analysis of joint effects showed that: (i) compared to pain-free physically active people, RRs in people with ≥5 chronic pain sites were 3.77 (95% CI: 2.42-5.85) if they were inactive and 2.76 (95% CI: 2.29, 3.31) if they were active; and (ii) compared to pain-free people with normal weight, RRs in people with ≥5 chronic pain sites were 3.52 (95% CI: 2.81, 4.40) if they were obese and 2.93 (95% CI: 2.24, 3.84) if they had normal weight. In conclusion, chronic musculoskeletal pain increases the risk of insomnia, particularly among those who report several pain sites. Although there was no clear evidence of modifying effects, our results suggest that a healthy active lifestyle reduces the risk of insomnia in people with chronic musculoskeletal pain.

Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

PURPOSE: This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. METHODS: Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. RESULTS: The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. CONCLUSIONS: A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. TRIAL REGISTRATION: clinicaltrials.gov : NCT02307721.

Physical work exposure, chronic musculoskeletal pain and risk of insomnia: longitudinal data from the HUNT study, Norway.

OBJECTIVES: To prospectively investigate (i) the association of physical work demands and work-related physical fatigue with risk of insomnia symptoms and (ii) if these associations are influenced by chronic musculoskeletal pain. METHODS: Prospective study on a working population of 8563 women and 7598 men participating in the Nord-Trøndelag Health Study (Norway) who reported no insomnia at baseline in 1995-1997. Occurrence of insomnia symptoms was assessed at follow-up in 2006-2008. A Poisson regression model was used to calculate adjusted risk ratios (RRs) for insomnia symptoms with 95% CI. RESULTS: Compared with workers without work-related physical fatigue, women and men who reported that they were always fatigued had RRs of insomnia of 2.34 (95% CI 1.72 to 3.18) and 2.47 (95% CI 1.59 to 3.83), respectively. Overall, physical work demands was not associated with risk of insomnia, although men who reported heavy physical work had an RR of 0.67 (95% CI 0.47 to 0.97) compared with men with mostly sedentary work. Compared with the reference group of workers without work-related physical fatigue and no chronic pain, analyses of joint effects showed that women with excessive work-related fatigue had an RR of 4.20 (95% CI 2.95 to 5.98) if they reported chronic pain and an RR of 1.67 (95% CI 0.87 to 3.18) if they did not. Corresponding RRs in men were 3.55 (95% CI 2.11 to 5.98) and 2.13 (95% CI 1.07 to 4.25). CONCLUSION: These findings suggest that there is an interplay between work-related physical fatigue and musculoskeletal pain that should receive particular attention in the prevention of insomnia in working populations.