Matthias Zunhammer

Reduced alcohol consumption in mice with access to a running wheel

Studies of the behavioral effects of alcohol in humans and rodent models have implicated a number of neurological pathways and genes. Separate studies have shown that certain regions of the brain are involved in behavioral responses to exercise. The aim of this study was to determine whether mice which normally voluntarily consume high amounts of alcohol (C57BL/6 strain) would exhibit reduced alcohol consumption when given access to a running wheel under two different models of voluntary consumption: unlimited access two-bottle choice and limited access drinking in the dark (DID). Under the two-bottle choice model, the animals voluntarily consumed less alcohol when a wheel was present in their cage. However, sex-specific differences emerged because female mice voluntarily consumed less alcohol when they have the opportunity to exercise on a running wheel, whereas male mice consumed less alcohol even if the running wheel was locked. There were no significant differences observed in alcohol metabolism or food consumption. Under the DID protocol, no differences in alcohol consumption were observed in the presence of a running wheel. These results suggest that exercise may be a useful approach to consider for treatment for some types of chronic human alcohol problem behaviors, but may be less applicable to human binge drinking.

Somatic Symptoms Evoked by Exam Stress in University Students: The Role of Alexithymia, Neuroticism, Anxiety and Depression

Objective The etiology of somatization is incompletely understood, but could be elucidated by models of psychosocial stress. Academic exam stress has effectively been applied as a naturalistic stress model, however its effect on somatization symptoms according to ICD-10 and DSM-IV criteria has not been reported so far. Baseline associations between somatization and personality traits, such as alexithymia, have been studied exhaustively. Nevertheless, it is largely unknown if personality traits have an explanatory value for stress induced somatization. Methods This longitudinal, quasi-experimental study assessed the effects of university exams on somatization — and the reversal of effects after an exam-free period. Repeated-observations were obtained within 150 students, measuring symptom intensity before, during and after an exam period, according to the Screening for Somatoform Symptoms 7-day (SOMS-7d). Additionally, self-reports on health status were used to differentiate between medically explained and medically unexplained symptoms. Alexithymia, neuroticism, trait-anxiety and baseline depression were surveyed using the Toronto-Alexithymia Scale (TAS-20), the Big-Five Personality Interview (NEO-FFI), the State Trait Anxiety Inventory (STAI) and Beck’s Depression Inventory (BDI-II). These traits were competitively tested for their ability to explain somatization increases under exam stress. Results Somatization significantly increased across a wide range of symptoms under exam stress, while health reports pointed towards a reduction in acute infections and injuries. Neuroticism, alexithymia, trait anxiety and depression explained variance in somatization at baseline, but only neuroticism was associated with symptom increases under exam stress. Conclusion Exam stress is an effective psychosocial stress model inducing somatization. A comprehensive quantitative description of bodily symptoms under exam stress is supplied. The results do not support the stress-alexithymia hypothesis, but favor neuroticism as a personality trait of importance for somatization.

Effects of intranasal oxytocin on thermal pain in healthy men: a randomized functional magnetic resonance imaging study.

Objective Intranasal oxytocin has been shown to affect human social and emotional processing, but its potential to affect pain remains elusive. This randomized, placebo-controlled, double-blind, crossover trial investigated the effect of intranasal oxytocin on the perception and processing of noxious experimental heat in 36 healthy male volunteers. Methods Thermal thresholds were determined according to the Quantitative Sensory Testing protocol. A functional magnetic resonance imaging experiment including intensity and unpleasantness ratings of tonic heat was used to investigate the effects of oxytocin within the brain. Results Thirty men (aged 18–50 years) were included in the study. Intranasal oxytocin had no significant effect on thermal thresholds, but significantly (t = −2.06, p = .046) reduced heat intensity ratings during functional magnetic resonance imaging. The effect on intensity ratings was small (−3.46 points on a 100-point visual analog scale [95% confidence interval {CI} = −6.86 to −0.07] and independent of temperature. No effects of oxytocin on stimulus- or temperature-related processing were found at the whole-brain level at a robust statistical threshold. A region of interest analysis indicated that oxytocin caused small but significant decreases in left (−0.045%, 95% CI = −0.087 to −0.003, t = −2.19, p = .037) and right (−0.051%, 95% CI = −0.088 to −0.014], t = −2.82, p = .008) amygdala activity across all temperatures. Conclusions The present study provides evidence for a significant but subtle inhibitory effect of oxytocin on thermal stimulus ratings and concurrent amygdala activity. Neither of the two effects significantly depended of temperature; therefore, the hypothesis of a pain-specific effect of oxytocin could not be confirmed. Trial Registration: EUDRA-CT 2009-015115-40

rTMS over the cerebellum modulates temperature detection and pain thresholds through peripheral mechanisms

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex has been shown to modulate pain perception. Even though evidence suggests an involvement of cerebellar structures in pain processing, the effect of rTMS over the cerebellum on pain perception has not yet been investigated. OBJECTIVE/HYPOTHESIS This study aimed to test the effects of rTMS over the cerebellum on sensory perception, particularly controlling for peripheral stimulation effects. METHODS Sensory perception was determined as temperature detection and temperature pain thresholds. Experiment one explored the effects of four different rTMS protocols (flat figure-of-eight coil; 120% motor resting threshold; 1000 stimuli; 1 Hz and 10 Hz; medial and right lateral cerebellum) on sensory thresholds in 10 healthy volunteers using pairwise comparisons. The most efficient protocol of experiment one was compared in a second experiment with two control conditions (rTMS with a sham coil over the cerebellum [sham] and repetitive magnetic stimulation [rMS] of the neck) by using robust statistics (MANOVA). RESULTS The first experiment demonstrated pronounced effects on sensory perception for 1Hz rTMS over the lateral cerebellum. The second experiment confirmed this result in comparison to sham. However, rMS over the neck had a similar effect like rTMS over the cerebellum. CONCLUSIONS Our findings suggest that changes in sensory perception after rTMS over the cerebellum are largely due to stimulation effects on peripheral structures and support recent reports of analgesic effects of neck rMS. They advocate the critical review of the proposed analgesic effects of rTMS and encourage the future use of proper control conditions in rTMS research.

Sleep Quality during Exam Stress: The Role of Alcohol, Caffeine and Nicotine

Academic exam stress is known to compromise sleep quality and alter drug consumption in university students. Here we evaluated if sleeping problems and changes in legal drug consumption during exam stress are interrelated. We used the Pittsburgh Sleep Quality Index (PSQI) to survey sleep quality before, during, and after an academic exam period in 150 university students in a longitudinal questionnaire study. Self-reports of alcohol, caffeine, and nicotine consumption were obtained. The Perceived Stress Questionnaire (PSQ-20) was used as a measure of stress. Sleep quality and alcohol consumption significantly decreased, while perceived stress and caffeine consumption significantly increased during the exam period. No significant change in nicotine consumption was observed. In particular, students shortened their time in bed and showed symptoms of insomnia. Mixed model analysis indicated that sex, age, health status, as well as the amounts of alcohol and caffeine consumed had no significant influence on global sleep quality. The amount of nicotine consumed and perceived stress were identified as significant predictors of diminished sleep quality. Nicotine consumption had a small-to-very-small effect on sleep quality; perceived stress had a small-to-moderate effect. In conclusion, diminished sleep quality during exam periods was mainly predicted by perceived stress, while legal drug consumption played a minor role. Exam periods may pose an interesting model for the study of stress-induced sleeping problems and their mechanisms.

Theory of Mind and Emotional Awareness in Chronic Somatoform Pain Patients.

Objective The present study aimed at investigating whether chronic pain patients are impaired in Theory of Mind (ToM), or Emotional Awareness. Methods Thirty inpatients suffering from chronic somatoform pain, as well as thirty healthy controls matched for age, sex, and education were recruited. ToM abilities were measured using the Frith-Happé animation task, in which participants interpret video-clips depicting moving geometric forms that mimic social interactions. The responses given were scored for appropriateness and the degree of inferred intentionality according to established protocols. Emotional awareness was measured using the Levels of Emotional Awareness Scale (LEAS), for which participants provide written descriptions of feelings in imaginary emotional situations. Standardized scoring was performed to capture the number and quality of emotional terms used. Results Responses lengths were similar in both groups and for both tasks. Patients attained significantly lower intentionality but not appropriateness scores when interpreting ToM interactions. No significant group differences were found when interpreting goal directed interactions. Emotional awareness scores were significantly lower in patients compared to healthy controls. Conclusions Our results suggest that chronic pain patients are impaired in mentalizing and emotional awareness. Future studies are needed to determine whether these ToM and emotional awareness deficits contribute to the etiology of somatoform pain and whether addressing these deficits in therapeutic interventions can improve polymodal pain therapy.

Do Cardiorespiratory Variables Predict the Antinociceptive Effects of Deep and Slow Breathing

UNLABELLED Deep and slow breathing (DSB) is a central part of behavioral exercises used for acute and chronic pain management. Its mechanisms of action are incompletely understood. OBJECTIVES 1) To test the effects of breathing frequency on experimental pain perception in a dose dependent fashion. 2) To test the effects of breathing frequency on cardiorespiratory variables hypothesized to mediate DSB analgesia. 3) To determine the potential of the cardiorespiratory variables to mediate antinociceptive DSB effects by regression analysis. DESIGN Single-blind, randomized, crossover trial. SUBJECTS Twenty healthy participants. INTERVENTIONS Visually paced breathing at 0.14 Hz, 0.10 Hz, 0.06 Hz, and resting frequency. OUTCOME MEASURES Cardiorespiratory variables: RR-interval (= 60 seconds/heart rate), standard deviation of the RR-interval (SDRR), and respiratory CO2 . Experimental pain measures: heat pain thresholds, cold pain thresholds, pain intensity ratings, and pain unpleasantness ratings. RESULTS 1) There was no effect of DSB frequency on experimental pain perception. 2) SDRR and respiratory CO2 were significantly modulated by DSB frequency, while RR-interval was not. 3) Baseline-to-DSB and session-to-session differences in RR-interval significantly predicted pain perception within participants: Prolonged RR-intervals predicted lower pain ratings, while shortened RR-intervals predicted higher pain ratings. SDRR and respiratory CO2 were not found to predict pain perception. CONCLUSIONS The present study could not confirm hypotheses that the antinociceptive effects of DSB are related to changes in breathing frequency, heart rate variability, or hypoventilation/hyperventilation when applied as a short-term intervention. It could confirm the notion that increased cardiac parasympathetic activity is associated with reduced pain perception.

Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the International Affective Pictures System (IAPS) with positive, neutral, and negative emotional valence were shown. Heat intensity and unpleasantness ratings were obtained. The activity of whole-brain correlates of heat processing was quantified via multi-voxel pattern analysis. We observed no appreciable main effects of oxytocin on ratings or neural pain correlates. Effects of emotional picture valence on ratings were smaller than reported in previous studies. Nevertheless, oxytocin was found to significantly enhance the influence of picture valence on unpleasantness ratings at noxious heat levels. No corresponding changes in whole-brain correlates of heat intensity processing were found. Our study provides evidence that intranasal oxytocin increases the effects of emotional context on the subjective unpleasantness of experimental heat pain. Future studies are needed to determine whether this effect can be utilized in clinical settings.