Experience of stress may lead to increased electromyography (EMG) activity in specific muscles compared to a non-stressful situation. The main aim of this study was to develop and validate a stress-EMG paradigm in which a single uncontrollable and unpredictable nociceptive stimulus was presented. EMG activity of the trapezius muscles was the response of interest. In addition to linear time effects, non-linear EMG time courses were also examined. Taking into account the hierarchical structure of the dataset, a multilevel random regression model was applied. The stress paradigm, executed in N = 70 subjects, consisted of a 3-minute baseline measurement, a 3-minute pre-stimulus stress period and a 2-minute post-stimulus phase. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. EMG activity during the entire experiment was conform a priori expectations: the pre-stimulus phase showed a significantly higher mean EMG activity level compared to the other two phases, and an immediate EMG response to the stimulus was demonstrated. In addition, the analyses revealed significant non-linear EMG time courses in all three phases. Linear and quadratic EMG time courses were significantly modified by subjective anticipatory stress level, measured just before the start of the stress task. Linking subjective anticipatory stress to EMG stress reactivity revealed that subjects with a high anticipatory stress level responded with more EMG activity during the pre-stimulus stress phase, whereas subjects with a low stress level showed an inverse effect. Results suggest that the stress paradigm presented here is a valid test to quantify individual differences in stress susceptibility. Further studies with this paradigm are required to demonstrate its potential use in mechanistic clinical studies.

The aim of this study was to investigate how perceived stress may affect electroencephalographical (EEG) activity in a stress paradigm in a sample of 76 healthy participants. EEG activity was analyzed using multilevel modeling, allowing estimation of nested effects (EEG time segments within subjects). The stress paradigm consisted of a 3-minute pre-stimulus stress period and a 2-minute post-stimulus phase. At t=3 minutes, a single electrical stimulus was delivered. Participants were unaware of the precise moment of stimulus delivery and its intensity level. In the EEG time course of alpha activity, a stronger increase was observed during the post-stimulus period as compared to the pre-stimulus period. An opposite time course effect was apparent for gamma activity. Both effects were in line with a priori expectations and support the validity of this experimental EEG-stress paradigm. Secondly, we investigated whether interaction effects of stress and coping, as measured with the Perceived Stress Scale-10 questionnaire (PSS-10), could be demonstrated. A higher perceived stress score was accompanied by a greater increase in delta- and theta-activity during the post-stimulus phase, compared to low scores. In contrast, low coping capacity was associated with a stronger decrease in slow beta, fast beta and gamma activity during the post-stimulus phase. The results of the present article may be interpreted as proof-of-principle that EEG stress-related activity depends on the level of subjectively reported perceived stress. The inclusion of psychosocial variables measuring coping styles as well as stress-related personality aspects permits further examination of the interconnection between mind and body and may inform on the process of transformation from acute to chronic stress.

Does pain hypervigilance further impact the lack of habituation to pain in individuals with chronic pain? A cross-sectional pain ERP study Catherine J Vossen,1 Rosan Luijcks,2 Jim van Os,2,3 Elbert A Joosten,1 Richel Lousberg2 1Department of Anaesthesiology and Pain Medicine, 2Department of Psychiatry & Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands; 3King’s College London, King’s Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, UK Aim: In chronic pain, habituation is believed to be impaired, and pain hypervigilance can enhance the pain experience. The goal of this study was to determine whether pain hypervigilance further worsens habituation of event-related potentials, measured in a pain-rating protocol of 25 painful somatosensory electrical stimuli, in patients with chronic pain. Methods: Pain hypervigilance was assessed with the Pain Vigilance Awareness Questionnaire and analyzed using the event-related fixed interval areas multilevel technique, which enables one to study within-session habituation. In a cohort of 111 participants, 33 reported chronic pain. This chronic pain group was compared with 33 pain-free individuals, matched for age and sex. Results: The relationship between pain status and habituation was not moderated by pain hypervigilance. Chronic pain status affected linear habituation and dishabituation (quadratic function) from 220 to 260 ms for nearly all electrodes, and from 580 to 640 ms for frontal electrodes. The effect of pain hypervigilance on habituation was observed primarily from 480 to 820 ms poststimulus for right-sided and central electrodes.Conclusion: Pain hypervigilance and chronic pain independently influence habituation to painful stimuli – although not synergistically. To confirm that these effects are mediated by separate pathways, further research is required, in which electroencephalography is combined with other modalities with adequate spatial resolution, such as functional magnetic resonance imaging. Keywords: event-related fixed-interval area, ERFIA, multilevel analysis, habituation, pain hypervigilance, chronic pain

In this review, the latest insights into habituation to pain in chronic pain are summarized. Using a systematic search, results of studies on the evidence of habituation to (experimental) pain in migraine, chronic low back pain, fibromyalgia, and a variety of chronic pain indications are presented. In migraine, reduced habituation based on self-report and the EEG-based N1 and N2–P2 amplitude is reported, but the presence of contradictory results demands further replication in larger, well-designed studies. Habituation to pain in chronic low back pain seems not to differ from controls, with the exception of EEG measures. In fibromyalgia patients, there is some evidence for reduced habituation of the N2–P2 amplitude. Our analysis shows that the variability between outcomes of studies on habituation to pain is high. As the mechanisms underlying habituation to pain are still not fully understood and likely involve several pathways, it is now too early to conclude that habituation to pain is related to clinical outcomes and can be used as a diagnostic marker. The review ends with a discussion on future directions for research including the use of standard outcome measures to improve comparisons of habituation to pain in patients and controls, as well as a focus on individual differences.

The objective of the present study was to investigate cortical differences between chronic low back pain (CLBP) subjects and pain-free controls with respect to habituation and processing of stimulus intensity. The use of a novel event-related fixed-interval areas (ERFIA) multilevel technique enables the analysis of event-related electroencephalogram (EEG) of the whole post stimulus range at a single trial level. This technique makes it possible to disentangle the cortical processes of habituation and stimulus intensity. In a cross-sectional study, 78 individuals with CLBP and 85 pain-free controls underwent a rating paradigm of 150 nonpainful and painful somatosensory electrical stimuli. For each trial, the entire epoch was partitioned into 20-ms ERFIAs, which acted as dependent variables in a multilevel analysis. The variability of each consecutive ERFIA period was modeled with a set of predictor variables, including 3 forms of habituation and stimulus intensity. Seventy-six pain-free controls and 65 CLBP subjects were eligible for analysis. CLBP subjects showed a significantly decreased linear habituation at 340 to 460 ms in the midline electrodes and C3 (Ps < .05) and had a significantly more pronounced dishabituation for the regions of 400 to 460 ms and 800 to 820 ms for all electrodes, except for T3 and T4 (Ps < .05). No significant group differences for stimulus intensity processing were observed. In this study, group differences with respect to linear habituation and dishabituation were demonstrated. By means of the ERFIA multilevel technique, habituation effects were found in a broad post stimulus range and were not solely limited to peaks. This study suggests that habituation may be a key mechanism involved in the transition process to chronic pain. Future studies with a longitudinal design are required to solve this issue.

BACKGROUND: There are concerns whether (repeated) exposure to general anaesthesia is associated with long-term cognitive decline. OBJECTIVE: We investigated the potential, negative relationship between total exposure to surgery under general anaesthesia and its impact on long-term cognitive development. DESIGN: A prospective longitudinal cohort study. SETTING: The Netherlands. PARTICIPANTS: 1823 Adults, aged 25–84 with normal cognitive functioning on inclusion with three serial cognitive assessments between 1995 and 2008, with comprehensive documentation on demographic, lifestyle, and health factors. MAIN OUTCOME MEASURES: The primary outcomes were test scores in the cognitive domains of learning and memory, executive function, selective attention, mental speed, and information processing speed. Linear mixed models were used to analyse the effects of the estimated total time under general anaesthesia at baseline on cognitive development during a 12-year follow-up period. RESULTS: When adjusting for demographic and systemic health-related factors, prolonged exposure to surgery under general anaesthesia (measured in total baseline minutes) negatively affected three cognitive domains. These included the CST (executive functioning, P < 0.05), Stroop (selective attention and mental speed, P < 0.001) and LDST (information processing speed, P < 0.005). Age and education were the primary factors impacting lifetime cognitive decline. Hypertension, diabetes, and smoking negatively affected various cognitive domains. CONCLUSION: Increased exposure to surgery under general anaesthesia independently contributes to long-term cognitive decline. Demographic variables and health-related factors are key contributors to accelerated cognitive decline over an individual's lifetime.