Shift work, inflammation and musculoskeletal pain-The HUNT Study.

BACKGROUND: Studies have indicated that shift work, in particular night work, is associated with chronic musculoskeletal pain but the mechanisms are unclear. It has been suggested that sleep disturbance, a common complaint among shift and night workers, may induce low-grade inflammation as well as heightened pain sensitivity. AIMS: Firstly, this study was aimed to examine the cross-sectional associations between shift work, C-reactive protein (CRP) level and chronic musculoskeletal pain, and secondly, to analyse CRP as a mediator between shift work and chronic musculoskeletal pain. METHODS: The study included 23 223 vocationally active women and men who participated in the HUNT4 Survey of the Trøndelag Health Study (HUNT). Information was collected by questionnaires, interviews, biological samples and clinical examination. RESULTS: Regression analyses adjusted for sex, age and education revealed significant associations between shift work and odds of any chronic musculoskeletal pain (odd ratio [OR] 1.11, 95% confidence interval [CI] 1.04-1.19), between shift work and CRP level (OR 1.09, 95% CI 1.03-1.16) and between CRP level 3.00-10 mg/L and any chronic musculoskeletal pain (OR 1.38, 95% CI 1.27-1.51). Shift work and CRP were also associated with number of chronic pain sites. Mediation analysis indicated that shift work was indirectly associated with any chronic musculoskeletal pain through CRP (OR 1.03, 95% CI 1.01-1.06). CONCLUSIONS: The results support the hypothesis that shift work is associated with chronic musculoskeletal pain, and that systemic inflammation may be a biological mechanism linking shift work to chronic pain.

Insomnia and risk of chronic musculoskeletal complaints: longitudinal data from the HUNT study, Norway.

BACKGROUND: The aim of this study was to investigate the prospective association between insomnia and risk of chronic musculoskeletal complaints (CMSC) and chronic widespread musculoskeletal complaints (CWMSC). A second aim was to evaluate the association between insomnia and number of body regions with CMSC at follow-up. METHODS: We used data from the second (HUNT2, 1995-1997) and third (HUNT3, 2006-2008) wave of the Nord-Trøndelag Health Study (the HUNT Study). The population-at-risk included 13,429 people aged 20-70 years who reported no CMSC at baseline in HUNT2 and who answered the questionnaires on insomnia in HUNT2 and CMSC in HUNT3. Insomnia was defined according to the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) with minor modification, whereas CMSC was assessed for nine different body regions. CWMSC was defined according to the 1990 criteria by the American College of Rheumatology. We used Poisson regression to estimate adjusted risk ratios (RRs) for CMSC and CWMSC at 11 years follow-up. Precision of the estimates was assessed by a 95% confidence interval (CIs). RESULTS: Insomnia at baseline was associated with increased risk of any CMSC (RR 1.16, 95% CI 1.03-1.32) and CWMSC (RR 1.58, 95% CI 1.26-1.98) at follow-up. RR for CMSC for specific body regions ranged from 1.34 (95% CI 1.05-1.73) for the knees and 1.34 (1.10-1.63) for the neck to 1.60 (95% CI 1.19-2.14) for the ankles/ft. Further, insomnia was associated with increased risk of CMSC in 3-4 regions (RR 1.36, 95% CI 1.05-1.77), and 5 or more regions (RR 1.93, 95% CI 1.40-2.66), but not 1-2 regions (RR 0.99, 95% CI 0.80-1.24). CONCLUSIONS: Insomnia is associated with increased risk of CMSC, CWMSC, and CMSC located in 3 or more body regions.

Sleep quality, arousal and pain thresholds in tension-type headache: a blinded controlled polysomnographic study.

INTRODUCTION: We aimed to compare subjective and objective sleep quality in tension-type headache (TTH) patients and to evaluate the relationship between sleep quality and pain thresholds (PT) in controls and TTH patients. METHODS: A blinded cross-sectional study where polysomnography (PSG) and PT (to pressure, heat and cold) measurements were done in 20 patients with TTH (eight episodic (ETTH) and twelve chronic (CTTH) TTH) and 29 healthy controls. Sleep diaries and questionnaires were applied. RESULTS: TTH patients had more anxiety ( P = 0.001), insomnia ( P < 0.0005), daytime tiredness ( P < 0.0005) and reduced subjective sleep quality ( P < 0.0005) compared to healthy controls. Sleep diaries revealed more long awakenings in TTH ( P = 0.01) but no total sleep-time differences. TTH patients had more slow-wave sleep ( P = 0.002) and less fast arousals ( P = 0.004) in their PSGs. CTTH subjects had lower pressure PT ( P = 0.048) and more daytime sleepiness than the controls ( P = 0.039). Among TTH lower cold PT (CPT) correlated inversely with light sleep (N1) ( R = -0.49, P = 0.003) while slow arousals correlated inversely with headache-frequency ( R = -0.64, P = 0.003). CONCLUSIONS: We hypothesize that TTH patients need more sleep than healthy controls and might be relatively sleep deprived. Inadequate sleep may also contribute to increased pain sensitivity and headache frequency in TTH.

Headache and insomnia in population-based epidemiological studies.

BACKGROUND: Several epidemiological studies on the association between primary headaches and insomnia have been published in recent years. Both disorders are frequent, and our purpose was to review results from population-based studies exploring this association. METHODS: We performed a literature search in PubMed for "insomnia" (or sleep disturbance) and "headache" (or migraine) linked with "epidemiology." Two hundred and eight records were identified. Three longitudinal and 10 cross-sectional studies met our inclusion criteria: population-based design with at least 200 participants including a numerical estimate of the association between headache and insomnia. RESULTS AND CONCLUSIONS: In nearly all studies, primary headaches, including migraine and tension-type headache, were significantly related to insomnia symptoms with OR estimates ranging from 1.4 to 1.7. The odds were even greater, from 2.0 to 2.6, for frequent, comorbid or severe headache. Recent large longitudinal studies from Norway found a bidirectional, possibly causal, association between headache and insomnia. However, not all studies used standardized diagnostic criteria for either headache or insomnia. Further research should use well defined and validated diagnostic criteria both for insomnia and headache types in order to improve the comparability between studies, investigate causality and clarify the relevance of the findings for clinical practice.

Harnessing historical data to derive reference limits - A comparison of e-norms to traditionally derived reference limits.

Objective: Nerve conduction studies (NCS) require valid reference limits for meaningful interpretation. We aimed to further develop the extrapolated norms (e-norms) method for obtaining NCS reference limits from historical laboratory datasets for children and adults, and to validate it against traditionally derived reference limits. Methods: We compared reference limits obtained by applying a further developed e-norms with reference limits from healthy controls for the age strata's 9-18, 20-44 and 45-60 years old. The control data consisted of 65 healthy children and 578 healthy adults, matched with 1294 and 5628 patients respectively. Five commonly investigated nerves were chosen: The tibial and peroneal motor nerves (amplitudes, conduction velocities, F-waves), and the sural, superficial peroneal and medial plantar sensory nerves (amplitudes, conduction velocities). The datasets were matched by hospital to ensure identical equipment and protocols. The e-norms method was adapted, and reference limit calculation using both ±2 SD (original method) and ±2.5 SD (to compensate for predicted underestimation of population SD by the e-norms method) was compared to control data using ±2 SD. Percentage agreement between e-norms and the traditional method was calculated. Results: On average, the e-norms method (mean ±2 SD) produced slightly stricter reference limits compared to the traditional method. Increasing the e-norms range to mean ±2.5 SD improved the results in children while slightly overcorrecting in the adult group. The average agreement between the two methods was 95 % (±2 SD) and 96 % (±2.5 SD). Conclusions: The e-norms method yielded slightly stricter reference limits overall than ones obtained through traditional methods; However, much of the difference can be attributed to a few outlying plots where the raters found it difficult to apply e-norms correctly. The two methods disagreed on classification of 4-5% of cases. Our e-norms software is suited to analyze large amounts of raw NCS data; it should further reduce bias and facilitate more accurate ratings. Significance: With small adaptations, the e-norms method adequately replicates traditionally derived reference limits, and is a viable method to produce reference limits from historical datasets.

Evening light environments can be designed to consolidate and increase the duration of REM-sleep.

Evening exposure to short-wavelength light has disruptive effects on circadian rhythms and sleep. These effects can be mitigated by blocking short-wavelength (blue) frequencies, which has led to the development of evening blue-depleted light environments (BDLEs). We have previously reported that residing 5 days in an evening BDLE, compared with residing in a normal indoor light environment of similar photopic lux, advances circadian rhythms and increases the duration of rapid eye movement (REM) sleep in a randomized cross-over trial with twelve healthy participants. The current study extends these findings by testing whether residing in the evening BDLE affects the consolidation and microstructure of REM sleep in the same sample. Evening BDLE significantly reduces the fragmentation of REM sleep (p = 0.0003), and REM sleep microarousals in (p = 0.0493) without significantly changing REM density or the latency to first REM sleep episode. Moreover, the increased accumulation of REM sleep is not at the expense of NREM stage 3 sleep. BDLE further has a unique effect on REM sleep fragmentation (p = 0.0479) over and above that of circadian rhythms phase-shift, indicating a non-circadian effect of BDLE. If these effects can be replicated in clinical populations, this may have a therapeutic potential in disorders characterized by fragmented REM sleep.

Quantitative EEG in type 1 diabetic adults with childhood exposure to severe hypoglycaemia: a 16 year follow-up study.

AIMS/HYPOTHESIS: In diabetic children and adolescents, a history of severe hypoglycaemia (SH) has been associated with increased slow EEG activity and reduced cognition, possibly due to harmful effects of SH on the developing brain. In a group of type 1 diabetic patients with early exposure to SH, who had EEG abnormalities and reduced cognition in childhood, we have recently demonstrated that the reduced cognition may persist into adulthood. We have now assessed whether the reduced cognition was accompanied by lasting EEG abnormalities. METHODS: In 1992-1993, we studied EEG and cognition in 28 diabetic children and 28 matched controls. 16 years later, we re-investigated the same participants, with 96% participation rate. Diabetic participants were classified as with (n = 9) or without (n = 18) early SH, defined as episodes with convulsions or loss of consciousness by 10 years of age. For each EEG band (delta, theta, alpha and beta) and cerebral region (frontocentral, temporal, and parietooccipital), we calculated relative amplitudes and amplitude asymmetry. We also calculated occipital alpha mean frequency, alpha peak frequency at maximum amplitude, alpha peak width, and theta regional mean frequencies. We examined whether these EEG measures, relative to age- and sex-matched controls, differed between diabetic participants with and without early SH. RESULTS: We found no association of early SH with any of the EEG measures. CONCLUSIONS/INTERPRETATION: Childhood SH was not associated with EEG abnormalities in young type 1 diabetic adults. Our findings suggest that the reduced adulthood cognition associated with childhood exposure to SH is not accompanied by lasting EEG abnormalities.

Photic EEG-driving responses related to ictal phases and trigger sensitivity in migraine: a longitudinal, controlled study.

INTRODUCTION: Photic driving is believed to be increased in migraineurs and has been interpreted as a sign of cortical hyperexcitability. However, most previous studies have included patients in various phases of the migraine cycle. The results are, therefore, difficult to interpret as neurophysiological abnormalities tend to accumulate close to the attack in migraineurs. SUBJECTS AND METHODS: We recorded steady state visual evoked EEG-responses (SSVEPs) for 6, 12, 18 and 24 Hz flash stimuli from 33 migraineurs without aura, eight migraineurs with aura and 32 healthy controls. Interictal recordings were compared pair-wise with recordings before, during and after attack, as well as with EEGs from healthy controls. Driving power was also correlated with sensory hypersensitivity and severity of migraine. RESULTS: Between attacks, driving responses to 18 Hz and 24 Hz were attenuated in migraineurs without aura. Driving power of 12 Hz increased before the attack. Attack trigger sensitivity, photophobia, pain intensity and a family history of migraine were related to decreased and/or symmetric photic driving. CONCLUSIONS: Earlier results may have overestimated the driving response in migraine due to inclusion of recordings during the preictal interval and/or habituation among controls. Abnormal photic driving may be related to the pathophysiology of clinical sensory hypersensitivity.

Neurophysiological tests and neuroimaging procedures in non-acute headache (2nd edition).

BACKGROUND AND PURPOSE: A large number of instrumental investigations are used in patients with non-acute headache in both research and clinical fields. Although the literature has shown that most of these tools contributed greatly to increasing understanding of the pathogenesis of primary headache, they are of little or no value in the clinical setting. METHODS: This paper provides an update of the 2004 EFNS guidelines and recommendations for the use of neurophysiological tools and neuroimaging procedures in non-acute headache (first edition). Even though the period since the publication of the first edition has seen an increase in the number of published papers dealing with this topic, the updated guidelines contain only minimal changes in the levels of evidence and grades of recommendation. RESULTS: (i) Interictal EEG is not routinely indicated in the diagnostic evaluation of patients with headache. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic or basilar migraine. (ii) Recording evoked potentials is not recommended for the diagnosis of headache disorders. (iii) There is no evidence warranting recommendation of reflex responses or autonomic tests for the routine clinical examination of patients with headache. (iv) Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pain threshold measurements and EMG are not recommended as clinical diagnostic tests. (v) In adult and pediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological symptoms or signs, the routine use of neuroimaging is not warranted. In patients with trigeminal autonomic cephalalgia, neuroimaging should be carefully considered and may necessitate additional scanning of intracranial/cervical vasculature and/or the sellar/orbital/(para)nasal region. In patients with atypical headache patterns, a history of seizures and/or focal neurological symptoms or signs, MRI may be indicated. (vi) If attacks can be fully accounted for by the standard headache classification (IHS), a PET or SPECT scan will normally be of no further diagnostic value. Nuclear medical examinations of the cerebral circulation and metabolism can be carried out in subgroups of patients with headache for the diagnosis and evaluation of complications, when patients experience unusually severe attacks or when the quality or severity of attacks has changed. (vii) Transcranial Doppler examination is not helpful in headache diagnosis. CONCLUSION: Although many of the examinations described in the present guidelines are of little or no value in the clinical setting, most of the tools, including thermal pain thresholds and transcranial magnetic stimulation, have considerable potential for differential diagnostic evaluation as well as for the further exploration of headache pathophysiology and the effects of pharmacological treatment.

Experimental sleep restriction increases latency jitter in pain elicited cortical responses.

OBJECTIVE: Previous studies have shown increased pain scores to painful stimulation after experimental sleep restriction, but reduced or unchanged magnitude of the event related potentials (ERPs) when averaged in the time-domain. However, some studies found increased response magnitude when averaging in the time-frequency domain. The aim of this study was to determine whether ERP-latency jitter may contribute to this discrepancy. METHODS: Ninety painful electrical stimuli were given to 21 volunteers after two nights of 50% sleep restriction and after two nights of habitual sleep. ERPs were analyzed in the time-domain (N2-and P2-peaks) and time-frequency domain (power spectral density). We quantified latency jitter by the mean consecutive difference (MCD) between single-trial peak latencies and by phase locking value (PLV) across trials. RESULTS: P2-MCD increased from 20.4 ± 2.1 ms after habitual sleep to 24.3 ± 2.2 ms after sleep restriction (19%, p = 0.038) and PLV decreased from 0.582 ± 0.015 after habitual sleep to 0.536 ± 0.015 after sleep restriction (7.9%, p = 0.009). We found no difference for N2-MCD. CONCLUSIONS: Our results indicate that partial sleep restriction increase latency jitter in cortical responses to experimental pain. SIGNIFICANCE: Latency jitter may contribute to the discrepancies between ERP-responses in the time-frequency domain and time-domain. Latency jitter should be considered when ERPs are analyzed.

Headache after concussion.

BACKGROUND AND PURPOSE: Chronic post-traumatic headache attributed to mild head injury is a somewhat disputed headache diagnosis. A main object of this study was to assess the validity of this diagnosis by studying the headache pattern of concussed patients that participated in one historic (n = 131) and one prospective cohort (n = 217) study. METHODS: Head injury patients were recruited from two hospitals in Kaunas, Lithuania. Controls were recruited amongst patients with minor orthopaedic traumas not involving the head and neck. RESULTS: When data from the two studies were pooled, no difference in any headache category (diagnosis, attack frequency, symptoms) was found one or more years after the trauma, except that photophobia was somewhat more prevalent amongst the concussed patients. In both injury groups, the existence of pre-traumatic headache was a predictor of post-traumatic headache, although pre-traumatic headache seems to have been underreported amongst the concussed patients. There was a significant negative correlation between the duration of unconsciousness and the headache. CONCLUSIONS: This negative correlation, and the lack of specificity indicates that headache occurring 3 months or more after concussion is not caused by the head or brain injury. Rather it may represent an episode of one of the primary headaches, possibly induced by the stress of the situation.

Increased baroreflex sensitivity and heart rate variability in migraine patients.

OBJECTIVES: We investigated whether spontaneous baroreflex sensitivity and heart rate variability (HRV) are different in migraine patients compared to healthy controls. MATERIAL AND METHODS: Sixteen female migraine patients without aura aged 18-30 years and 14 age-matched healthy female controls were included. Continuous finger blood pressure and ECG were measured supine during paced breathing in the laboratory. Continuous finger blood pressure was measured the following 24-h period. Spontaneous baroreflex sensitivity (time-domain cross correlation baroreflex sensitivity) as well as HRV parameters were calculated. RESULTS: Spontaneous baroreflex sensitivity measured in the 24-h period was increased in patients (20.6 ms/mmHg) compared to controls (15.7 ms/mmHg, P = 0.031). HRV parameters were increased during paced breathing in patients (P < 0.045). CONCLUSIONS: The results suggest that central hypersensitivity in migraine also includes cardiovascular reactivity and may be important for the understanding of the mechanisms for the effect of antihypertensive drugs for migraine prophylaxis.

The relationship between obstructive sleep apnea and insomnia: a population-based cross-sectional polysomnographic study.

BACKGROUND: The relationship between insomnia and objectively measured obstructive sleep apnea (OSA) severity has not previously been investigated in both genders in the general population. The main aim of this population-based polysomnography (PSG) study was to evaluate the cross-sectional association between severity of OSA and DSM-V insomnia and insomnia severity. METHODS: A random sample of 1200 participants in the third Nord-Trøndelag Health Study (HUNT3) was invited and 213 (18%) aged between 21 and 82 years underwent an ambulatory PSG, a semi-structured interview, and a sleep-specific questionnaire. A proxy DSM-V insomnia diagnosis as well as an Insomnia Symptom Score (ISS, range 0-12) were calculated from three insomnia questions and one daytime sleepiness symptom question. Participants were then divided into three groups according to their apnea-hypopnea index (AHI): AHI < 5 (without OSA), AHI 5-14.9 (mild OSA), and AHI ≥ 15 (moderate-to-severe OSA). Associations between prevalence of insomnia and OSA groups were assessed by logistic regression models adjusted for age and gender. Associations between ISS and OSA were assessed in a general linear model with contrasts. RESULTS: A total of 25.2% (29.1% women, 12.5% men) had insomnia. Insomnia prevalence did not differ between subjects with and without OSA, but ISS differed significantly between OSA categories (ANCOVA df 2, F = 6.73, p = 0.001). ISS was lower in the moderate-to-severe OSA-group compared to those without OSA (mean difference -2.68; 95% [CI -4.33, -1.04]; p = 0.002). In subjects with moderate-to-severe OSA, ISS correlated negatively with age (Pearson r = -0.66, p = 0.015). CONCLUSION: In this population-based PSG study, no overall statistical association between OSA and insomnia prevalence was found. However, participants with moderate-to-severe OSA reported less insomnia symptoms than subjects without OSA, in particular in older individuals.

A prospective three-year follow-up study on the clinical significance of anti-neuronal antibodies in acute psychiatric disorders.

The clinical significance of anti-neuronal antibodies for psychiatric disorders is controversial. We investigated if a positive anti-neuronal antibody status at admission to acute psychiatric inpatient care was associated with a more severe neuropsychiatric phenotype and more frequent abnormalities during clinical work-up three years later. Patients admitted to acute psychiatric inpatient care who tested positive for N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2) and/or glutamic acid decarboxylase 65 (GAD65) antibodies (n = 24) were age - and sex matched with antibody-negative patients (1:2) from the same cohort (n = 48). All patients were invited to follow-up including psychometric testing (e.g. Symptom Checklist-90-Revised), serum and cerebrospinal fluid (CSF) sampling, EEG and 3 T brain MRI. Twelve antibody-positive (ab+) and 26 antibody-negative (ab-) patients consented to follow-up. Ab+ patients had more severe symptoms of depression (p = 0.03), psychoticism (p = 0.04) and agitation (p = 0.001) compared to ab- patients. There were no differences in CSF analysis (n = 6 ab+/12 ab-), EEG (n = 7 ab+/19 ab-) or brain MRI (n = 7 ab+/17 ab-) between the groups. In conclusion, anti-neuronal ab+ status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at three-year follow-up. This supports the hypothesis that anti-neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients.

Quantitative EEG power and asymmetry increase 36 h before a migraine attack.

The aim was to estimate ictal, pre- and postictal brain function changes in migraine in a blinded paired quantitative EEG (QEEG) study. EEG recordings (n = 119) from 40 migraineurs were retrospectively classified as ictal, interictal, preictal or postictal. delta, theta, alpha and beta power, and hemispheric asymmetry in frontocentral, temporal and occipitoparietal regions were calculated from artefact-free EEG. Power and power asymmetry were calculated for two time-windows, 36 and 72 h before/after the attack, and compared with the interictal values. Frontocentral delta power increased (P = 0.03), whereas frontocentral theta and alpha power tended to increase (P < 0.09) within 36 h before the next attack compared with the interictal period. Occipitoparietal (alpha and theta) and temporal (alpha) power were more asymmetric before the attack compared with the interictal baseline (P < 0.04). Ictal posterior alpha power increased slightly (P = 0.01). Postictal power and power asymmetry were not significantly different from interictal baseline. EEG activity seems to change shortly before the attack. This suggests that migraineurs are most susceptible to attack when anterior QEEG delta power and posterior alpha and theta asymmetry values are high. Changed activity patterns in cholinergic brainstem or basal forebrain nuclei and thalamo-cortical connections before the migraine attack are hypothesized.

Thermal pain thresholds are decreased in the migraine preattack phase.

BACKGROUND AND PURPOSE: Migraine patients may have cutaneous allodynia during attacks. In order to investigate if pain physiology changes in the preattack phase we estimated heat pain and cold pain detection threshold (HPT and CPT) on three different days in 41 migraine patients and 28 controls. METHODS: A thermode was applied at four sites bilaterally: forehead, face, neck, and hand. A subgroup of 11 migraine patients had been tested within 24 h before their next attack and in the interictal phase. RESULTS: In the preattack phase, HPT was lower compared with the paired interictal recording for the hand (44.8 degrees C vs. 45.9 degrees C, P = 0.009), neck (46.8 degrees C vs. 48.2 degrees C, P = 0.02), and forehead (45.1 degrees C vs. 46.3 degrees C, P = 0.02). Neck and hand CPT were higher in the preattack phase than interictally (10 degrees C vs. 7.3 degrees C, P = 0.01 and 11.6 degrees C vs. 9.4 degrees C, P = 0.06, respectively). Preattack forehead changes were most apparent on the headache side of the subsequent attack. DISCUSSION: Subclinical preattack thermal pain hypersensitivity seems to be a feature of the process that leads to a migraine attack.

Reduced motor cortical inhibition in migraine: A blinded transcranial magnetic stimulation study.

OBJECTIVE: To investigate motor cortical excitability, inhibition, and facilitation with navigated transcranial magnetic stimulation (TMS) in migraine in a blinded cross-sectional study. METHODS: Resting motor threshold (RMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were compared in 27 interictal migraineurs and 33 controls. 24 female interictal migraineurs and 27 female controls were compared in subgroup analyses. Seven preictal migraineurs were also compared to the interictal group in a hypothesis-generating analysis. Investigators were blinded for diagnosis during recording and analysis of data. RESULTS: SICI was decreased in interictal migraineurs when compared to healthy controls (p=0.013), CSP was shortened in female interictal migraineurs (p=0.041). ICF was decreased in preictal compared to interictal migraineurs (p=0.023). RMT and ICF were not different between interictal migraineurs and controls. CONCLUSION: Cortical inhibition was decreased in migraineurs between attacks, primarily in a female subgroup, indicating an importance of altered cortical inhibition in migraine. SIGNIFICANCE: Previous studies on motor cortical excitability in migraineurs have yielded varying results. This relatively large and blinded study provides support for altered cortical inhibition in migraine. Measuring intracortical facilitation in the period preceding migraine attacks may be of interest for future studies.

Pain induced by low-grade stress in patients with fibromyalgia and chronic shoulder/neck pain, relation to surface electromyography.

The mechanisms of pain causation in fibromyalgia (FMS) and chronic shoulder/neck pain (SNP) are still debated. We wanted to compare muscle activity and pain development during and after low-grade mental stress in FMS and SNP patients. Twenty-three women with FMS, 29 women with chronic SNP and 35 healthy women performed a stressful task lasting 60 min followed by a 30 min recovery period. We recorded surface electromyography over the trapezius, neck, temporalis and frontalis muscles. Subjects reported their pain at the corresponding locations together with the development of fatigue and perceived tension. Significant differences between FMS and SNP groups were not observed either for muscular or subjective responses. SNP patients and controls responded with more pain in the trapezius and neck regions than in the forehead, in contrast to FMS patients who had a more generalized pain response. Development of pain, tension and fatigue was not related to muscle activity for any group. We conclude that FMS and SNP patients have similar pain and electromyographic responses. The results suggest that similar pathophysiological mechanisms are involved although the responses are more generalised in FMS than in SNP patients. Muscular activity did not explain the pain which developed during the stressful task for either group. Pain lasted longer during recovery in both FMS and SNP patients compared to healthy controls, possibly a result of disease-related sensitisation in pain pathways.

Examination of the diagnostic validity of 'headache attributed to whiplash injury': a controlled, prospective study.

Acute and chronic headache attributed to whiplash injury are new diagnostic entities in the International Classification of Headache Disorders, second edition. A main objective of the present study was to assess the validity of these nosologic entities by studying the headache pattern in an inception cohort of 210 rear-end car collision victims and in 210 matched controls. Consecutive drivers involved in rear-end collisions were identified from the daily records of the Traffic Police Department of Kaunas, Lithuania. A standard self-report questionnaire was sent to the drivers between 2 and 7 days after the collision, and their passengers were recruited as well. Headache and neck pain were evaluated within 7 days of the collision, at 2 months and 1 year after the collision. A control group of non-traumatized subjects received questionnaires at the time of the selection and 1 year later. Of the 75 collision victims who developed headache within the first 7 days of the collision, 37 had a clinical picture in accordance with the criteria for acute whiplash headache (i.e., concomitant neck pain) and 38 did not. For acute headache after collision, concomitant neck pain was of no relevance to the headache type or its course. In both these subgroups, migraine and tension-type headache could be diagnosed in similar proportions and the prognosis after 2 months and 1 year was also similar. Preexisting headache was a strong prognostic factor in both groups for both acute and chronic pain. Compared with the non-traumatized control group, the 1-year incidence of new or worsened headache, or of headache improvement, was the same. A likely interpretation of the data is that acute headaches after rear-end car collisions mainly represent episodes of a primary headache precipitated by the stress of the situation. We conclude that the nosologic validity of both acute and chronic whiplash headache is poor as the headaches, in accordance with the criteria lack distinguishing clinical features and have the same prognosis compared with headaches in a control group.

Effects of butyrate on epidermal growth factor receptor binding, morphology, and DNA synthesis in cultured rat hepatocytes.

We have examined the effect of butyrate on morphology, DNA synthesis, and epidermal growth factor (EGF) receptor binding in primary cultures of rat hepatocytes. Butyrate added 2 h after plating retarded the flattening and maintained the polyhedral shape of the hepatocytes in culture. Both insulin- and EGF-stimulated DNA syntheses were slightly stimulated by butyrate at 1 mM but strongly inhibited at 5 mM. EGF receptor binding was also strongly affected by butyrate treatment of the hepatocytes. The freshly isolated hepatocytes (prior to plating) and the early-stage cultures (2 h) exhibited two classes of surface EGF receptors with high and low affinity (Kd approximately 0.05 and approximately 0.7 nM, respectively). With increasing time in culture there was a decrease in the total EGF receptor number and a corresponding reduction in the capacity for receptor-mediated EGF internalization. The high-affinity receptor class was more strongly reduced than the low-affinity class and was almost absent after 40 h in culture. Butyrate dose-dependently counteracted the decrease in the number of surface EGF receptors during culturing and preserved the high-affinity binding component. Thus, after 40 h, the cells cultured in the presence of butyrate (5 mM) had an approximately 50% elevation in the total number of receptors and the capacity to endocytose EGF compared to control cells, whereas the binding at low ligand concentration (0.02 nM) was increased 4-fold. The results suggest that butyrate, in addition to affecting morphology and DNA synthesis, also has marked effects on the hepatocyte EGF receptor status.