Evaluation of a multimodal stress management and comprehensive lifestyle modification program on quality-of-life and gastrointestinal symptoms in patients with Crohn's Disease - A randomized controlled pilot trial with nine-month follow-up.

BACKGROUND: Stress and lifestyle factors impact the course of Crohn's Disease (CD). Our primary objective was to assess whether patients with CD benefit from a mind-body-medicine stress management and lifestyle modification (MBM) program. METHODS: This 9-month two-arm pilot trial was conducted in Bamberg, Germany (2020-2021). Patients (18-75 years) with mild to moderate activity of CD and stable medication were enrolled and randomly assigned to either a 10-week MBM program (intervention group, IG) or a single 90-minutes education session (waiting list control group, CG). Primary endpoints were quality of life (IBDQ) and disease activity (HBI). Secondary endpoints were emotional distress, core self-evaluation, and inflammatory biomarkers 3 and 9 months after baseline assessment. RESULTS: We analysed data from thirty-seven patients (IG: n=19, mean±SD age 49.6±13.1 years, 68% female; CG: 18, 46.8±11.4, 67% female). Immediately after the intervention, 79% (IG) and 44% (CG) experienced a clinically relevant improvement (IBDQ score ≥16 points). This was similar after 9 months (63% vs 44%). There was no difference in disease activity (3 months: p=.082, 95%CI -1.3-2.6; 9 months: p=.251, 95%CI -1.2-2.5). Secondary outcomes indicated improvements in emotional distress, core self-evaluation, erythrocyte sedimentation rate after three and in emotional distress, T-cell-profiling in the blood, and fecal lactoferrin and calprotectin group after 9 months in the intervention group. CONCLUSION: Our study suggested benefits of a multimodal stress management and lifestyle modification program for patients with CD. Larger trials are needed to determine if the program can supplement or at least partially replace pharmacological treatment approaches. CLINICALTRIALS: gov ID: NCT05182645.

[Pain is modality-specific : Differences in the perception and processing of interoceptive visceral compared to exteroceptive cutaneous heat pain stimuli]. / Schmerz ist modalitätsspezifisch : Unterschiede in der Wahrnehmung und Verarbeitung interozeptiver viszeraler im Vergleich zu exterozeptiven kutanen thermischen Schmerzreizen.

Interoceptive visceral pain is perceived as more fear-inducing and unpleasant compared to cutaneous heat pain in healthy women even when stimuli are matched for perceived pain intensity. On a neural level, both pain stimuli induce comparable neural activation in areas related to processing of sensory-discriminative pain aspects. However, enhanced neural responses are observed in areas associated with salience processing and descending pain inhibition for the visceral pain modality, even when results are controlled for intra-individual differences in perceived pain intensity. Moreover, immanent fear of pain is suggested to play a distinctive role in perception of visceral pain.

Randomised clinical trial: yoga vs written self-care advice for ulcerative colitis.

BACKGROUND: Perceived stress seems to be a risk factor for exacerbation of ulcerative colitis. Yoga has been shown to reduce perceived stress. AIMS: To assess the efficacy and safety of yoga for improving quality of life in patients with ulcerative colitis. METHODS: A total of 77 patients (75% women; 45.5 ± 11.9 years) with ulcerative colitis in clinical remission but impaired quality of life were randomly assigned to yoga (12 supervised weekly sessions of 90 min; n = 39) or written self-care advice (n = 38). Primary outcome was disease-specific quality of life (Inflammatory Bowel Disease Questionnaire). Secondary outcomes included disease activity (Rachmilewitz clinical activity index) and safety. Outcomes were assessed at weeks 12 and 24 by blinded outcome assessors. RESULTS: The yoga group had significantly higher disease-specific quality of life compared to the self-care group after 12 weeks (Δ = 14.6; 95% confidence interval=2.6-26.7; P = 0.018) and after 24 weeks (Δ = 16.4; 95% confidence interval=2.5-30.3; P = 0.022). Twenty-one and 12 patients in the yoga group and in the self-care group, respectively, reached a clinical relevant increase in quality of life at week 12 (P = 0.048); and 27 and 17 patients at week 24 (P = 0.030). Disease activity was lower in the yoga group compared to the self-care group after 24 weeks (Δ = -1.2; 95% confidence interval=-0.1-[-2.3]; P = 0.029). Three and one patient in the yoga group and in the self-care group, respectively, experienced serious adverse events (P = 0.317); and seven and eight patients experienced nonserious adverse events (P = 0.731). CONCLUSIONS: Yoga can be considered as a safe and effective ancillary intervention for patients with ulcerative colitis and impaired quality of life. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02043600.

Learning by experience? Visceral pain-related neural and behavioral responses in a classical conditioning paradigm.

BACKGROUND: Studies investigating mechanisms underlying nocebo responses in pain have mainly focused on negative expectations induced by verbal suggestions. Herein, we addressed neural and behavioral correlates of nocebo responses induced by classical conditioning in a visceral pain model. METHODS: In two independent studies, a total of 40 healthy volunteers underwent classical conditioning, consisting of repeated pairings of one visual cue (CSHigh ) with rectal distensions of high intensity, while a second cue (CSLow ) was always followed by low-intensity distensions. During subsequent test, only low-intensity distensions were delivered, preceded by either CSHigh or CSLow . Distension intensity ratings were assessed in both samples and functional magnetic resonance imaging data were available from one study (N=16). As a consequence of conditioning, we hypothesized CSHigh -cued distensions to be perceived as more intense and expected enhanced cue- and distension-related neural responses in regions encoding sensory and affective dimensions of pain and in structures associated with pain-related fear memory. KEY RESULTS: During test, distension intensity ratings did not differ depending on preceding cue. Greater distension-induced neural activation was observed in somatosensory, prefrontal, and cingulate cortices and caudate when preceded by CSHigh . Analysis of cue-related responses revealed strikingly similar activation patterns. CONCLUSIONS & INFERENCES: We report changes in neural activation patterns during anticipation and visceral stimulation induced by prior conditioning. In the absence of behavioral effects, markedly altered neural responses may indicate conditioning with visceral signals to induce hypervigilance rather than hyperalgesia, involving altered attention, reappraisal, and perceptual acuity as processes contributing to the pathophysiology of visceral pain.

What Makes You Feel Sick After Inflammation? Predictors of Acute and Persisting Physical Sickness Symptoms Induced by Experimental Endotoxemia.

We aimed to identify statistical predictor variables of lipopolysaccharide (LPS)-induced physical sickness symptoms during the acute and late inflammatory phases using multivariate regression analyses. Data from N = 128 healthy volunteers who received i.v. LPS injection (0.4 or 0.8 ng/kg) or placebo were pooled for analyses. Physical sickness symptoms experienced during the acute (0-6h postinjection) and late (6-24h postinjection) phases were assessed with the validated General-Assessment-of-Side-Effects (GASE) questionnaire. LPS-treated subjects reported significantly more physical sickness symptoms. Physical symptoms during the acute phase were associated with LPS-induced mood impairments and interleukin (IL)-6 increases, explaining 28.5% of variance in GASE scores. During late phase, LPS-induced increases in cortisol and IL-6 plasma concentrations and baseline depression were significant predictor variables, explaining 38.5% of variance. In patients with recurrent or chronic inflammatory states, these factors may act as risk factors ultimately contributing to an exacerbation of sickness symptoms, and should be considered as potential targets for therapeutic strategies.

Altered Cerebellar Activity in Visceral Pain-Related Fear Conditioning in Irritable Bowel Syndrome.

There is evidence to support a role of the cerebellum in emotional learning processes, which are demonstrably altered in patients with chronic pain. We tested if cerebellar activation is altered during visceral pain-related fear conditioning and extinction in irritable bowel syndrome (IBS). Cerebellar blood oxygenation level-dependent (BOLD) data from N = 17 IBS patients and N = 21 healthy controls, collected as part of a previous fMRI study, was reanalyzed utilizing an advanced normalizing method of the cerebellum. The differential fear conditioning paradigm consisted of acquisition, extinction, and reinstatement phases. During acquisition, two visual conditioned stimuli (CS) were presented either paired (CS+) or unpaired (CS-) with painful rectal distension as unconditioned stimulus (US). In the extinction phase, the CS+ and CS- were presented without US. For reinstatement, unpaired US presentations were followed by unpaired CS+ and CS- presentations. Group differences in cerebellar activation were analyzed for the contrasts CS+ > CS- and CS- > CS+. During acquisition, IBS patients revealed significantly enhanced cerebellar BOLD responses to pain-predictive (CS+) and safety (CS-) cues compared to controls (p < 0.05, family-wise error corrected). Increased activation was found in three main clusters, including the vermis (maximum in vermal lobule VI), intermediate cerebellum (maximum in lobule VIII), and the posterolateral cerebellar hemisphere (maximum in lobule VI). Areas overlapped for the contrasts CS+ > CS- and CS- > CS+. Group differences were most prominent in the contrast CS- > CS+. During extinction and reinstatement, no significant group differences were found. During visceral pain-related fear conditioning, IBS patients showed increased activations in circumscribed areas of the medial, intermediate, and lateral cerebellum. These areas are involved in autonomic, somatosensory, and cognitive functions and likely contribute to the different aspects of pain-related fear. The cerebellum contributes to altered pain-related fear learning in IBS.

[Psychobiological mechanisms in the pathophysiology of chronic visceral pain]. / Psychobiologische Mechanismen bei der Pathophysiologie chronischer viszeraler Schmerzen.

Although visceral pain is of high clinical relevance, it remains poorly understood especially when compared to somatic pain. Nevertheless, interdisciplinary research approaches bridging psychophysiology and neurogastroenterology have contributed to a more refined knowledge about the complex peripheral and central mechanisms of the bidirectional brain-gut axis in recent years. This review summarizes current knowledge regarding psychobiological mechanisms in the pathophysiology of chronic visceral pain in functional gastrointestinal disorders with a focus on irritable bowel syndrome (IBS). Special attention is paid to the role of affective disturbances and emotions, particularly psychological stress as well as to influences of cognition and learning on gastrointestinal motor and sensory functions in healthy individuals and patients with IBS. In this emerging field of research, new evidence from the fields of placebo research and pain-related fear conditioning provide new insights into the psychological and neurobiological mechanisms involved in the transition from acute to chronic pain and the maintenance of pain. This opens up new perspectives for innovative treatment approaches for IBS and other functional gastrointestinal disorders.

[Visceral pain]. / Viszeraler Schmerz.

Chronic visceral pain is an unresolved neurobiological, medical and socioeconomic challenge. Up to 20% of the adult population suffer from chronic visceral pain and abdominal complaints constitute a prevalent symptom also in children and adolescents. Existing treatment approaches are often unsuccessful and patients typically suffer from multiple somatic and psychological symptoms. This complex situation requires integrative treatment approaches. This review summarizes current basic and clinical research on acute and chronic visceral pain with a focus on research groups in Germany. Despite significant clinical and scientific advances, a number of questions remain open calling for more funding to support research to elucidate the complex pathophysiology of chronic visceral pain and to develop and test new treatment approaches. Research support should focus on interdisciplinary concepts and methodology using expertise from multiple disciplines. The field would also benefit from a broader integration of visceral pain into teaching curricula in medicine and psychology and should aim to motivate young clinicians and scientists to strive for a career within this important and highly fascinating area.

Prospective evaluation of follow-up in melanoma patients in Germany - results of a multicentre and longitudinal study.

BACKGROUND: Patient numbers requiring long-term melanoma surveillance are constantly rising. Surveillance is costly and guideline recommendations vary substantially. METHODS: In this German nationwide study, information on surveillance and treatment of patients diagnosed with melanoma and melanoma in situ (MMis) between April and June 2008 was prospectively collected over four years. Additionally, patient self-report questionnaires were evaluated to assess anxiety, depression, health-related quality of life, socio-demographic information and use of disease specific health information sources at year 4 after primary diagnosis. RESULTS: Complete data was available for 668 patients from 67 centres, of whom 96.0% were in regular melanoma surveillance. In year 3-4 of surveillance, only 55.6% of locoregionary metastases were detected during surveillance visits. Only 33.3% were self-detected by the patient even though 69.4% were documented as being clinically visible or palpable. Costs of 4year surveillance of 550 patients without tumour recurrence (stage I-IIC and MMis) accumulated to 228,155.75 €. Guideline-adherence for follow-up frequency, lymph node ultrasound, S100 serum level tests and diagnostic imaging recommendations was approximately 60% in year 3-4 of surveillance. Multivariate regression analysis showed that certain patient/tumour characteristics and regional differences were significantly associated with guideline deviations. The percentage of patients who exceeded published cut-off scores indicating clinically relevant symptoms of anxiety and depression were significantly increased. Patients frequently reported lack of psychosocial support and education but ascribed great importance to these. CONCLUSIONS: We recommend further reduction of melanoma follow-up in low-risk melanoma patients and improvement of psycho-social support and patient education for all melanoma patients.

Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome.

BACKGROUND: Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm. METHODS: During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses. KEY RESULTS: Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement. CONCLUSIONS & INFERENCES: Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS.

Are there sex differences in placebo analgesia during visceral pain processing? A fMRI study in healthy subjects.

BACKGROUND: We explored sex differences in the neural mechanisms mediating placebo analgesia in an established visceral pain model involving painful rectal distensions in healthy volunteers. METHODS: N = 15 men and N = 15 women underwent three consecutive functional magnetic resonance imaging sessions during which cued painful rectal distensions were delivered. After an adaptation session, positive expectations were induced with deceptive instructions regarding administration of an analgesic drug (placebo session). In the other session (control), truthful information about an inert substance was given. Sex differences in placebo-induced modulation of neural activation during anticipation and pain were analyzed along with ratings of expected and perceived pain intensity. KEY RESULTS: Placebo-induced reductions in pain ratings were comparable between men and women. At the level of the brain, group comparisons with respect to differences between the placebo and control conditions revealed greater modulation of the posterior insula (regions-of-interest analysis: pFWE < 0.05) and dorsolateral prefrontal cortex (whole-brain analysis: p < 0.001, uncorrected) during pain anticipation in women. During pain, placebo-induced down-regulation of the insula was altered in women compared to men (ROI analysis: pFWE < 0.05). CONCLUSIONS & INFERENCES: Our data provide first evidence supporting sex differences in pain-induced neural modulation during visceral placebo analgesia despite similar placebo-induced reductions in perceived pain intensity. These preliminary findings might contribute to elucidating mechanisms mediating placebo effects in clinical conditions associated with chronic abdominal pain such as in irritable bowel syndrome.

Biological and psychological predictors of visceral pain sensitivity in healthy premenopausal women.

BACKGROUND: Factors that are associated with pain perception remain incompletely understood, especially in the visceral pain field. Therefore, the current study aimed to investigate possible psychological and biological predictors of visceral pain sensitivity in healthy subjects. METHODS: In a sample of 59 healthy premenopausal female subjects on hormonal contraceptives, measures of gastrointestinal (GI) symptoms in daily life, trait and state anxiety, depression, serum cortisol concentrations and serum levels of interleukin-6 (IL-6) were obtained, followed by assessment of rectal distension pain sensitivity measures (i.e., rectal distension sensory threshold, pain threshold and pain ratings for discrete rectal distension stimuli). RESULTS: Regression analyses showed that more GI symptoms in daily life predicted a lower pain threshold. Higher levels of state anxiety predicted a lower pain threshold. Higher cortisol concentrations predicted lower pain ratings. IL-6 was positively related to GI symptoms but was a non-significant predictor of pain threshold in the multiple regression analysis. CONCLUSIONS: Similar to findings in patients with functional GI symptoms, we showed that subclinical GI symptoms predict visceral pain sensitivity. In line with somatic pain findings, state but not trait anxiety was found to predict visceral pain sensitivity. Our finding on serum cortisol as positive predictor of pain sensitivity might be interpreted in light of immunosuppressive effects of cortisol. Our finding on the role of IL-6 in GI symptoms is promising for understanding GI complaints in patients and needs further investigation.

Perceived treatment group affects behavioral and neural responses to visceral pain in a deceptive placebo study.

BACKGROUND: To assess effects of perceived treatment (i.e. drug vs placebo) on behavioral and neural responses to rectal pain stimuli delivered in a deceptive placebo condition. METHODS: This fMRI study analyzed the behavioral and neural responses during expectation-mediated placebo analgesia in a rectal pain model. In N = 36 healthy subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful stimulation was measured after participants were informed that they had a 50% chance of receiving either a potent analgesic drug or an inert substance (i.e., double-blind administration). In reality, all received placebo. We compared responses in subjects who retrospectively indicated that they received the drug and those who believed to have received placebo. KEY RESULTS: 55.6% (N = 20) of subjects believed that they had received a placebo, whereas 36.1% (N = 13) believed that they had received a potent analgesic drug. Subjects who were uncertain (8.3%, N = 3) were excluded. Rectal pain-induced discomfort was significantly lower in the perceived drug treatment group (P < 0.05), along with significantly reduced activation of the insular, the posterior and anterior cingulate cortices during pain anticipation, and of the anterior cingulate cortex during pain (all P < 0.05 in regions-of-interest analyses). CONCLUSIONS & INFERENCES: Perceived treatment constitutes an important aspect in placebo analgesia. A more refined understanding of individual treatment expectations and perceived treatment allocation has multiple implications for the design and interpretation of clinical trials and experimental studies on placebo and nocebo effects.

How positive and negative expectations shape the experience of visceral pain: an experimental pilot study in healthy women.

BACKGROUND: In order to elucidate placebo and nocebo effects in visceral pain, we analyzed the effects of positive and negative expectations on rectal pain perception, rectal pain thresholds, state anxiety and cortisol responses in healthy women. METHODS: Painful rectal distensions were delivered at baseline, following application of an inert substance combined with either positive instructions of pain relief (placebo group, N = 15), negative instructions of pain increase (nocebo group, N = 17), or neutral instructions (control, N = 15). Perceived pain intensity, unpleasantness/aversion and urge-to-defecate, state anxiety and serum cortisol were determined at baseline, immediately following group-specific instructions and on a second study day after the same instructions (test day). Rectal pain thresholds were determined at baseline and on the test day. KEY RESULTS: Whereas perceived pain intensity was significantly decreased in the placebo group, the nocebo group revealed significantly increased pain intensity ratings, along with significantly greater anticipatory anxiety on the test day (all P < 0.05 vs controls). Cortisol concentrations were significantly increased in the nocebo group following treatment but not on the test day. CONCLUSIONS & INFERENCES: The experience of abdominal pain can be experimentally increased or decreased by inducing positive or negative expectations. Nocebo effects involve a psychological stress response, characterized by increased anticipatory anxiety. These findings further underscore the role of cognitive and emotional factors in the experience of visceral pain, which has implications for the pathophysiology and treatment of patients with chronic abdominal complaints.

Behavioural and neural correlates of visceral pain sensitivity in healthy men and women: does sex matter?

INTRODUCTION: We assessed sex differences in behavioural and neural responses to rectal pain stimuli in healthy subjects. METHODS: In age- and body mass index-matched healthy subjects (n = 15 men, 15 women), rectal sensory and pain thresholds were assessed with a pressure-controlled barostat device. The blood oxygen level-dependent response during cued anticipation and painful stimulation was measured using functional magnetic resonance imaging (fMRI). Retrospective pain evaluations were accomplished with visual analogue scales. For fMRI data, region-of-interest (ROI) analyses and additional whole-brain analyses were carried out. RESULTS: There were no sex differences in rectal thresholds or pain ratings. ROI analyses revealed comparable distension-induced activation of the thalamus, somatosensory cortex, insula and dorsolateral prefrontal cortex (DLPFC). Only in additional whole-brain analyses did we find increased activation in women in DLPFC and middle temporal gyrus during pain anticipation and in the cerebellum and medial frontal gyrus during pain. A significant inverse association between rectal pain threshold and distension-induced activation in virtually all ROIs was found in women. In men, pain thresholds and insula activation were positively correlated, as were pain ratings and anterior cingulate cortex activation. CONCLUSIONS: Healthy men and women do not differ in behavioural measures of visceral pain sensitivity. The pattern of neural activation is comparable in the majority of pain-processing brain regions, although women may differ in the activation of DLPFC which could reflect sex differences in cognitive-emotional pain regulation. Women with lower pain thresholds showed greater neural responses, which may be relevant in the pathophysiology of visceral hyperalgesia.

Subclinical depressive symptoms affect responses to acute psychosocial stress in healthy premenopausal women.

Subclinical depressive symptoms constitute a primary risk factor for major depression as well as for cardiovascular conditions, which may be mediated by endocrine or immune alterations. The aim of this study was to assess the association between the extent of subclinical depressive symptoms and neuroendocrine and immune cell responses to acute psychosocial stress in healthy females. In N = 33 healthy premenopausal women, state anxiety, plasma adrenocorticotropic hormone and serum cortisol, and interleukin-6 (IL-6) concentration responses to public speaking stress were assessed. Beck depression inventory (BDI) scores were entered as a covariate in the analyses. The IL-6 response was significantly associated with BDI scores (p < 0.05). Secondary analyses revealed that women with more subclinical depressive symptoms demonstrated a reduced stress-induced increase in circulating IL-6 level (p < 0.05). By contrast, stress-induced neuroendocrine activation was not associated with depressive symptoms. Hence, subclinical depressive symptoms were associated with IL-6 responses to stress in young, healthy women. Unexpectedly, there was a reduced increase of serum IL-6 level in response to stress. Effects of depressive symptoms on the IL-6 response to stress may differ between subclinical and major depression.

Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study.

OBJECTIVE: To address the role of anxiety and depression symptoms in altered pain processing in irritable bowel syndrome (IBS). DESIGN: In this functional magnetic resonance imaging study, the blood oxygen level-dependent (BOLD) response to rectal distensions delivered at previously determined individual discomfort thresholds was assessed. PATIENTS: 15 female patients with irritable bowel syndrome (IBS) and with normal rectal pain thresholds, and 12 healthy women. MEASURES: The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences in pain-induced brain activation with and without controlling for HADS scores were evaluated. RESULTS: Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively, as confounding variables led to a loss of significant group differences. CONCLUSIONS: Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affective-motivational aspects of the pain response.

Effects of psychological stress on the cerebral processing of visceral stimuli in healthy women.

The aim of the study was to analyse effects of psychological stress on the neural processing of visceral stimuli in healthy women. The brain functional magnetic resonance imaging blood oxygen level-dependent response to non-painful and painful rectal distensions was recorded from 14 healthy women during acute psychological stress and a control condition. Acute stress was induced with a modified public speaking stress paradigm. State anxiety was assessed with the State-Trait-Anxiety Inventory; chronic stress was measured with the Perceived Stress Questionnaire. During non-painful distensions, activation was observed in the right posterior insular cortex (IC) and right S1. Painful stimuli revealed activation of the bilateral anterior IC, right S1, and right pregenual anterior cingulate cortex. Chronic stress score was correlated with activation of the bilateral amygdala, right posterior IC (post-IC), left periaqueductal grey (PAG), and right dorsal posterior cingulate gyrus (dPCC) during non-painful stimulation, and with activation of the right post-IC, right PAG, left thalamus (THA), and right dPCC during painful distensions. During acute stress, state anxiety was significantly higher and the acute stress - control contrast revealed activation of the right dPCC, left THA and right S1 during painful stimulation. This is the first study to demonstrate effects of acute stress on cerebral activation patterns during visceral pain in healthy women. Together with our finding that chronic stress was correlated wit the neural response to visceral stimuli, these results provide a framework for further studies addressing the role of chronic stress and emotional disturbances in the pathophysiology of visceral hyperalgesia.