The psychobiological model of disorders of gut-brain interaction: introduction of a novel, integrated, and testable model.

Psychogastroenterology encompasses both basic mechanistic research, which identifies psychological mechanisms (eg, fear-learning) that contribute to disorders of gut-brain interaction (DGBIs), and clinical applied research, which evaluates the efficacy of gut-brain behavioural therapies in DGBIs. However, progress in the field is hindered by inadequate communication between these areas, such that mechanistic processes are rarely translated into clinical targets, and interventions are developed with an incomplete understanding of the potential mechanisms by which they work or for whom they work. To bridge this translational gap, we propose the psychobiological model of DGBIs-an integrated and testable model that illustrates how psychological mechanisms central to DGBIs interact with each other and with biological processes along the gut-brain axis.

Neural correlates of human fear conditioning and sources of variability in 2199 individuals.

Pavlovian fear conditioning is a fundamental process in both health and disease. We investigate its neural correlates and sources of variability using harmonized functional magnetic resonance imaging data from 2199 individuals across nine countries, including 1888 healthy individuals and 311 with anxiety-related or depressive disorders. Using mega-analysis and normative modeling, we show that fear conditioning consistently engages brain regions within the "central autonomic-interoceptive" or "salience" network.

Placebo effects improve sickness symptoms and drug efficacy during systemic inflammation: a randomized controlled trial in human experimental endotoxemia.

Background: Systemic inflammation triggers a wide range of sickness symptoms, including bodily discomfort and affective symptoms, which are relevant to numerous health conditions. While extensive research in the placebo field demonstrates that positive expectations can improve symptoms, it remains unclear if interventions designed to augment positive treatment expectations can alleviate sickness symptoms in the context of immunomodulatory drug therapies.

Methods: In this randomized, controlled, fully balanced 2 × 2 factorial placebo design, N = 124 healthy volunteers received either active ibuprofen treatment (600 mg per os) or placebo, combined with either a positive or neutral labeling of the treatment by the physician.

Costly pain avoidance and its impact on the modulation and extinction of visceral pain-related fear.

Along the gut-brain axis, visceral pain demonstrably evokes emotional learning and memory processes shaping behavior in clinically relevant ways. Avoidance motivated by learned fear may constitute a major obstacle to treatment success in extinction-based interventions. However, the effects of avoidance on visceral pain-related fear extinction remain poorly understood.

Sex differences in the reactivity of gastric myoelectrical activity and heart rate variability as putative psychophysiological markers in human pain research.

Background: This study explored the potential of electrogastrography (EGG) and heart rate variability (HRV) as psychophysiological markers in experimental pain research related to the gut-brain axis. We investigated responses to the experience of pain from the visceral (rectal distension) and somatic (cutaneous heat) pain modalities, with a focus on elucidating sex differences in EGG and HRV responses.

Methods: In a sample of healthy volunteers (29 males, 43 females), EGG and ECG data were collected during a baseline and a pain phase.

Corrigendum: Preoperative Anxiolysis and Treatment Expectation (PATE Trial): open-label placebo treatment to reduce preoperative anxiety in female patients undergoing gynecological laparoscopic surgery - study protocol for a bicentric, prospective, randomized-controlled trial.

[This corrects the article DOI: 10.3389/fpsyt.2024.

"Powerful placebo": A teaching and learning concept addressing placebo and nocebo effects in competency-based communication training.

Aim: Placebo and nocebo effects are based on expectations that are formed by how doctors communicate and can influence the efficacy of medical treatment. Given the implications for doctor-patient communication and the learning objectives listed in NKLM 2.0, we herein present a novel teaching and learning concept to impart competency-based knowledge about placebo and nocebo effects.

Setting the stage for pain relief: how treatment setting impacts interdisciplinary multimodal pain treatment for patients with chronic back pain.

While interdisciplinary multimodal pain treatment (IMPT) is an effective treatment option for chronic low back pain, it is usually accomplished as an inpatient treatment incurring substantial healthcare costs. Day hospital IMPT could be a resource-saving alternative approach, but whether treatment setting is associated with differences in treatment outcomes has not yet been studied. In a retrospective matched cohort study including data from N = 595 patients diagnosed with chronic back pain and undergoing IMPT at the back pain center in Essen, Germany, we investigated the association between treatment setting (ie, inpatient or day patient of an otherwise identical IMPT) and pain intensity, disability, and self-efficacy after treatment.

Preoperative Anxiolysis and Treatment Expectation (PATE Trial): open-label placebo treatment to reduce preoperative anxiety in female patients undergoing gynecological laparoscopic surgery - study protocol for a bicentric, prospective, randomized-controlled trial.

One of the most common concerns of patients undergoing surgery is preoperative anxiety, with a prevalence of up to 48%. The effects of preoperative anxiety continue beyond the preoperative period and are associated with more severe postoperative pain and poorer treatment outcomes. Treatment options for preoperative anxiety are often limited as sedatives cause side effects and their efficacy remains controversial.

An externally validated resting-state brain connectivity signature of pain-related learning.

Pain can be conceptualized as a precision signal for reinforcement learning in the brain and alterations in these processes are a hallmark of chronic pain conditions. Investigating individual differences in pain-related learning therefore holds important clinical and translational relevance. Here, we developed and externally validated a novel resting-state brain connectivity-based predictive model of pain-related learning.

Treatment Expectations-You Get What You Expect-and Depression Plays a Role.

Positive treatment expectations demonstrably shape treatment outcomes regarding pain and disability in patients with chronic low back pain. However, knowledge about positive and negative treatment expectations as putative predictors of interindividual variability in treatment outcomes is sparse, and the role of other psychological variables of interest, especially of depression as a known predictor of long-term disability, is lacking. We present results of the first prospective study considering expectations in concert with depression in a sample of 200 patients with chronic low back pain undergoing an inpatient interdisciplinary multimodal pain therapy.

Disease-specific alterations in central fear network engagement during acquisition and extinction of conditioned interoceptive fear in inflammatory bowel disease.

Interoceptive fear, which is shaped by associative threat learning and memory processes, plays a central role in abnormal interoception and psychiatric comorbidity in conditions of the gut-brain axis. Although animal and human studies support that acute inflammation induces brain alterations in the central fear network, mechanistic knowledge in patients with chronic inflammatory conditions remains sparse. We implemented a translational fear conditioning paradigm to elucidate central fear network reactivity in patients with quiescent inflammatory bowel disease (IBD), compared to patients with irritable bowel syndrome (IBS) and healthy controls (HC).

Pre-treatment expectations and their influence on subjective symptom change in Crohn's disease.

Background: Treatment expectations reportedly shape treatment outcomes, but have not been studied in the context of multimodal therapy in Crohn's disease (CD). Therefore, the current study investigated the role of treatment expectations for subjective symptom changes in CD patients who have undergone an integrative multimodal therapy program.

Methods: Validated questionnaires were completed at the start of the treatment program and post intervention.

Hydrocortisone Differentially Affects Reinstatement of Pain-related Responses in Patients With Chronic Back Pain and Healthy Volunteers.

Despite the crucial role of effective and sustained extinction of conditioned pain-related fear in cognitive-behavioral treatment approaches for chronic pain, experimental research on extinction memory retrieval in chronic pain remains scarce. In healthy populations, extinction efficacy of fear memory is affected by stress. Therefore, we investigated the effects of oral hydrocortisone administration on the reinstatement of pain-related associations in 57 patients with non-specific chronic back pain (CBP) and 59 healthy control (HC) participants in a differential pain-related conditioning paradigm within a placebo-controlled, randomized, and double-blind design.

Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study 'NoVis'.

The role of psychological factors in the pathophysiology and treatment of chronic visceral pain in disorders of gut-brain interactions (DGBI) is increasingly appreciated. Placebo research has underscored that expectations arising from the psychosocial treatment context and from prior experiences shape treatment responses. However, effects of negative expectations, i.

Amplified gut feelings under inflammation and depressed mood: A randomized fMRI trial on interoceptive pain in healthy volunteers.

Background: Inflammation and depressed mood constitute clinically relevant vulnerability factors for enhanced interoceptive sensitivity and chronic visceral pain, but their putative interaction remains untested in human mechanistic studies. We tested interaction effects of acute systemic inflammation and sad mood on the expectation and experience of visceral pain by combining experimental endotoxemia with a mood induction paradigm.

Methods: The double-blind, placebo-controlled, balanced crossover fMRI-trial in N = 39 healthy male and female volunteers involved 2 study days with either intravenous administration of low-dose lipopolysaccharide (LPS, 0.

Distinct Alterations in Central Pain Processing of Visceral and Somatic Pain in Quiescent Ulcerative Colitis Compared to Irritable Bowel Syndrome and Health.

Background And Aims: Despite relevance to pain chronicity, disease burden, and treatment, mechanisms of pain perception for different types of acute pain remain incompletely understood in patients with inflammatory bowel disease [IBD]. Building on experimental research across pain modalities, we herein addressed behavioural and neural correlates of visceral versus somatic pain processing in women with quiescent ulcerative colitis [UC] compared to irritable bowel syndrome [IBS] as a patient control group and healthy women [HC].

Methods: Thresholds for visceral and somatic pain were assessed with rectal distensions and cutaneous thermal pain, respectively.

Inflammation shapes neural processing of interoceptive fear predictors during extinction learning in healthy humans.

Inflammation could impact on the formation and persistence of interoceptive fear and hypervigilance, with relevance to psychiatric disorders and chronic pain. To systematically analyze effects of inflammation on fear learning and extinction, we performed two complementary randomized, double-blind, placebo-controlled functional magnetic resonance imaging (fMRI) studies combining experimental endotoxemia as a translational model of acute systemic inflammation with a two-day multiple-threat fear conditioning paradigm involving interoceptive and exteroceptive unconditioned stimuli (US). Healthy volunteers (N = 95) were randomized to receive intravenous injections of either endotoxin (lipopolysaccharide, LPS; 0.

Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis.

Background: Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response.

Methods: We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo.

Circulating Pro-inflammatory Cytokines Do Not Explain Interindividual Variability in Visceral Sensitivity in Healthy Individuals.

A role of the immune system in the pathophysiology of pain and hyperalgesia has received growing attention, especially in the context of visceral pain and the gut-brain axis. While acute experimental inflammation can induce visceral hyperalgesia as part of sickness behavior in healthy individuals, it remains unclear if normal plasma levels of circulating pro-inflammatory cytokines contribute to interindividual variability in visceral sensitivity. We herein compiled data from a tightly screened and well-characterized sample of healthy volunteers ( = 98) allowing us to assess associations between visceral sensitivity and gastrointestinal symptoms, and plasma concentrations of three selected pro-inflammatory cytokines (i.

Greater interruption of visual processing and memory encoding by visceral than somatic pain in healthy volunteers - An fMRI study.

Visceral pain is regarded as more salient than somatic pain. It has greater affective and emotional components, i.e.

Positive Treatment Expectations Shape Perceived Medication Efficacy in a Translational Placebo Paradigm for the Gut-Brain Axis.

Placebo research has established the pivotal role of treatment expectations in shaping symptom experience and patient-reported treatment outcomes. Perceived treatment efficacy constitutes a relevant yet understudied aspect, especially in the context of the gut-brain axis with visceral pain as key symptom. Using a clinically relevant experimental model of visceral pain, we elucidated effects of pre-treatment expectations on post-treatment perceived treatment efficacy as an indicator of treatment satisfaction in a translational placebo intervention.

Temporal dynamics of fMRI signal changes during conditioned interoceptive pain-related fear and safety acquisition and extinction.

Associative learning and memory mechanisms drive interoceptive signaling along the gut-brain axis, thus shaping affective-emotional reactions and behavior. Specifically, learning to predict potentially harmful, visceral pain is assumed to succeed within very few trials. However, the temporal dynamics of cerebellar and cerebral fMRI signal changes underlying early acquisition and extinction of learned fear signals and the concomitant evolvement of safety learning remain incompletely understood.