Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.

(1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS.

Effect of slow, deep breathing on visceral pain perception and its underlying psychophysiological mechanisms.

BACKGROUND: Studies using somatic pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on visceral pain and explored putative mediating mechanisms including autonomic and emotional responses. METHODS: Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition. KEY RESULTS: Compared to uncontrolled breathing, pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on pain was not mediated by alterations in heart rate variability or arousal but was moderated by pain catastrophizing. CONCLUSIONS AND INFERENCES: Slow, deep breathing can reduce visceral pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) visceral pain warrants to be investigated.

Psychophysiological responses to various slow, deep breathing techniques.

Deep breathing exercises are commonly used for several health conditions including pain and hypertension. Various techniques are available to practice deep breathing, whereas possible differential psychophysiological effects have not been investigated. We compared four deep breathing techniques and examined outcomes in blood pressure variability, respiratory sinus arrhythmia, baroreflex function, and emotional state. Healthy adult volunteers performed pursed-lips breathing, left and right unilateral nostril breathing, and deep breathing with an inspiratory threshold load (loaded breathing), all at a frequency of 0.1 Hz (i.e., controlled breathing) and for three minutes each. Results showed that blood pressure variability was higher during loaded breathing versus other conditions and higher during pursed-lips breathing versus left and right unilateral nostril breathing. Respiratory sinus arrhythmia was higher during loaded breathing versus other conditions and higher during pursed-lips breathing versus left unilateral nostril breathing. The effect of breathing condition on respiratory sinus arrhythmia was mediated by alterations in blood pressure variability. There was no difference between the breathing conditions in baroreflex sensitivity or effectiveness. Participants rated pursed-lips breathing as more calming and pleasant and with more sense of control (vs. other conditions). Overall, among the four tested deep breathing techniques, loaded breathing was associated with enhanced cardiovascular effects and pursed-lips breathing with better emotional responses, while also enhancing cardiovascular effects (albeit less than loaded breathing). These findings can be informative in applying deep breathing techniques as self-management interventions for health conditions, in which baroreceptors stimulation and autonomic and emotional modulations can be beneficial, such as pain and hypertension.

Nutritional intervention in chronic pain: an innovative way of targeting central nervous system sensitization?

INTRODUCTION: Few treatment programs for chronic pain nowadays take a dietary pattern or adipose status into account. AREAS COVERED: An important role of neuroinflammation in chronic pain is now well established, at least in part due to increased central nervous system glial activation. Based on preclinical studies, it is postulated that the interaction between nutrition and central sensitization is mediated via bidirectional gut-brain interactions. This model of diet-induced neuroinflammation and consequent central sensitization generates a rationale for developing innovative treatments for patients with chronic pain. Methods: An umbrella approach to cover the authors' expert opinion within an evidence-based viewpoint. EXPERT OPINION: A low-saturated fat and low-added sugar dietary pattern potentially decreases oxidative stress, preventing Toll-like receptor activation and subsequent glial activation. A low-saturated fat and low-added sugar diet might also prevent afferent vagal nerve fibers sensing the pro-inflammatory mediators that come along with a high-(saturated) fat or energy-dense dietary pattern, thereby preventing them to signal peripheral inflammatory status to the brain. In addition, the gut microbiota produces polyamines, which hold the capacity to excite N-methyl-D-aspartate receptors, an essential component of the central nervous system sensitization. Hence, a diet reducing polyamine production by the gut microbiota requires exploration as a therapeutic target for cancer-related and non-cancer chronic pain.

Can Slow Deep Breathing Reduce Pain? An Experimental Study Exploring Mechanisms.

Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed 4 breathing patterns: 1) unpaced breathing, 2) paced breathing (PB) at the participant's spontaneous breathing frequency, 3) SDB at 6 breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at 6 breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of 3 different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to unpaced breathing, participants reported less intense pain during each of the 3 instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. PERSPECTIVES: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.

Influence of inspiratory threshold load on cardiovascular responses to controlled breathing at 0.1 Hz.

Slow, deep breathing is being used as a self-management intervention for various health conditions including pain and hypertension. Stimulation of the arterial baroreceptors and increased vagal modulation are among the proposed mechanisms for the therapeutic effects of slow, deep breathing. We investigated whether adding inspiratory threshold load can enhance the cardiovascular responses to controlled breathing at the frequency of 0.1 Hz, a common form of slow, deep breathing. Healthy volunteers (N = 29) performed controlled breathing at 0.1 Hz (6 breaths/minute) without load and with inspiratory threshold loads of 5 cmH2 O and 10 cmH2 O. Respiratory airflow, heart rate, and blood pressure were continuously recorded. The amplitude of the systolic blood pressure variation during respiratory cycles increased with increasing loads. Respiratory sinus arrhythmia was higher during controlled breathing at 0.1 Hz with the load of 10 cmH2 O compared to without load. Baroreflex sensitivity was not affected by loads. The effect of loads on respiratory sinus arrhythmia was mediated by increasing the amplitude of systolic blood pressure variation during respiratory cycles. These results suggest that applying small inspiratory threshold loads during controlled breathing at 0.1 Hz increases cardiac vagal modulation by this breathing exercise. This effect seems to be mediated by stronger stimulation of the arterial baroreceptors because of larger systolic blood pressure swings along the respiratory cycle. The potential benefit of long-term practice of controlled breathing at 0.1 Hz with inspiratory threshold loads on baroreflex function and cardiac vagal control needs to be investigated, particularly in pain and hypertension patients.

Altered gray matter volume in sensorimotor and thalamic regions associated with pain in localized provoked vulvodynia: a voxel-based morphometry study.

Multimodal neuroimaging studies provide support for a role of alterations in sensory processing circuits and endogenous pain modulatory systems in provoked vestibulodynia (PVD). In this study, we tested the hypotheses that PVD compared with healthy controls (HCs) would demonstrate gray matter volume (GMV) alterations in regions associated with sensorimotor, corticothalamic, and basal ganglia circuits. We also tested the replicability of previously reported gray matter increases in basal ganglia and hippocampal volumes in PVD vs HCs. In addition, disease specificity of GMV alterations were examined by comparing PVD with another chronic pain disorder. Finally, we examine whether GMV alterations are correlated with symptom measures. Structural magnetic resonance imaging was obtained in 119 premenopausal women (45 PVD, 45 HCs, and 29 irritable bowel syndrome [IBS]). A voxel-based morphometry analysis was applied to determine group differences in the hypothesized regions of interest. Compared with HCs, PVD women exhibited greater GMV in the basal ganglia, hippocampus, and sensorimotor cortices. Compared to patients with IBS, women with PVD had greater GMV in the hippocampus, and sensorimotor network, but lower GMV in the thalamus and precentral gyrus. Regional GMV alterations were associated with patient reports of pain during intercourse and muscle tenderness. The current findings provide further evidence that GMV is increased in PVD compared with HCs in several regions of the sensorimotor network and the hippocampus in patients with PVD. In addition, GMV distinct alterations in the sensorimotor network were identified between 2 pelvic pain disorders, PVD compared with IBS.

Review article: treatment options for functional dyspepsia.

BACKGROUND: Functional dyspepsia, consisting of epigastric pain syndrome and postprandial distress syndrome, is a prevalent functional gastrointestinal disorder. To date, only limited treatment options are available and conflicting results in terms of efficacy have been reported. Consequently, nonpharmacological treatment options are increasingly being explored for functional dyspepsia. AIM: To provide an overview of current pharmacological and nonpharmacological treatment options for functional dyspepsia. METHODS: A literature search was conducted on Pubmed and other sources to identify relevant studies. RESULTS: Acid suppressive therapy reduced symptoms in 30%-70% of the patients, with higher benefit in epigastric pain syndrome and superior effectiveness for proton pump inhibitors compared to H2 -antagonists. Prokinetic agents, primarily used to treat postprandial distress syndrome, showed variable efficiency: 59%-81% responder rate for dopamine receptor antagonists, 32%-91% for serotonin-4-receptor agonists and 31%-80% for muscarinic receptor antagonists. H Pylori eradication, recommended in infected patients, was effective in 24%-82%. Refractory symptoms are addressed with neuromodulators. However, their efficacy in functional dyspepsia remains incompletely elucidated, available data showing symptom reduction in 27%-71% of the patients. Regarding herbal agents, peppermint oil reduced symptoms in 66%-91%, rikkunshito in 29%-34% and iberogast in 20%-95%. Lastly, acupuncture, cognitive behavioural therapy and hypnotherapy may help to provide symptom control, but research on their efficacy remains sparse. CONCLUSIONS: None of the available therapies is effective in the majority of patients without being associated with major side effects. Developing new treatment options is challenging due to the heterogeneity of functional dyspepsia, the lack of readily identified target mechanisms and the poor association between pathophysiological disturbances and symptoms.

A mind cleared by walnut oil: The effects of polyunsaturated and saturated fat on extinction learning.

The treatment of anxiety-based psychopathology often hinges upon extinction learning. Research in nutritional neuroscience has observed that the regular consumption of perilla oil (50% alpha-linolenic acid (ALA)) facilitates extinction learning in rats (Yamamoto et al., 1988). However, acute facilitation of extinction learning by oils rich in ALA has not been reported for rats or humans, though the acute consumption of rapeseed oil (10% ALA) has been observed to improve cognitive processing speed in humans (Jones, Sünram-Lea, & Wesnes, 2012). For this reason, the present laboratory work examined the effects of adding walnut oil (12% ALA) to a chocolate milkshake on the acquisition, generalization, and extinction of a fear-based prediction in young adults. It compared performance between subjects. The other participants consumed a similar milkshake with either an equicaloric amount of cream (saturated fat), or with no added fat (control). Acquisition and generalization of the fear-based prediction were similar for all groups. However, those who consumed walnut oil extinguished most rapidly and profoundly. Implications for extinction learning are discussed.

Biased Intensity Judgements of Visceral Sensations After Learning to Fear Visceral Stimuli: A Drift Diffusion Approach.

A growing body of research has identified fear of visceral sensations as a potential mechanism in the development and maintenance of visceral pain disorders. However, the extent to which such learned fear affects visceroception remains unclear. To address this question, we used a differential fear conditioning paradigm with nonpainful esophageal balloon distensions of 2 different intensities as conditioning stimuli (CSs). The experiment comprised of preacquisition, acquisition, and postacquisition phases during which participants categorized the CSs with respect to their intensity. The CS+ was always followed by a painful electrical stimulus (unconditioned stimulus) during the acquisition phase and in 60% of the trials during postacquisition. The second stimulus (CS-) was never associated with pain. Analyses of galvanic skin and startle eyeblink responses as physiological markers of successful conditioning showed increased fear responses to the CS+ compared with the CS-, but only in the group with the low-intensity stimulus as CS+. Computational modeling of response times and response accuracies revealed that differential fear learning affected perceptual decision-making about the intensities of visceral sensations such that sensations were more likely to be categorized as more intense. These results suggest that associative learning might indeed contribute to visceral hypersensitivity in functional gastrointestinal disorders. PERSPECTIVE: This study shows that associative fear learning biases intensity judgements of visceral sensations toward perceiving such sensations as more intense. Learning-induced alterations in visceroception might therefore contribute to the development or maintenance of visceral pain.

Startle responding in the context of visceral pain.

This study aimed to investigate affective modulation of eye blink startle by aversive visceral stimulation. Startle blink EMG responses were measured in 31 healthy participants receiving painful, intermittent balloon distentions in the distal esophagus during 4 blocks (positive, negative, neutral or no pictures), and compared with startles during 3 'safe' blocks without esophageal stimulations (positive, negative or neutral emotional pictures). Women showed enhanced startle during blocks with distentions (as compared with 'safe' blocks), both when the balloon was in inflated and deflated states, suggesting that fear and/or expectations may have played a role. Men's startle did not differ between distention and non-distention blocks. In this particular study context affective picture viewing did not further impose any effect on startle eye blink responses. The current results may contribute to a better understanding of emotional reactions to aversive interoceptive stimulation.

The relevance of the philosophical 'mind-body problem' for the status of psychosomatic medicine: a conceptual analysis of the biopsychosocial model.

Psychosomatic medicine, with its prevailing biopsychosocial model, aims to integrate human and exact sciences with their divergent conceptual models. Therefore, its own conceptual foundations, which often remain implicit and unknown, may be critically relevant. We defend the thesis that choosing between different metaphysical views on the 'mind-body problem' may have important implications for the conceptual foundations of psychosomatic medicine, and therefore potentially also for its methods, scientific status and relationship with the scientific disciplines it aims to integrate: biomedical sciences (including neuroscience), psychology and social sciences. To make this point, we introduce three key positions in the philosophical 'mind-body' debate (emergentism, reductionism, and supervenience physicalism) and investigate their consequences for the conceptual basis of the biopsychosocial model in general and its 'psycho-biological' part ('mental causation') in particular. Despite the clinical merits of the biopsychosocial model, we submit that it is conceptually underdeveloped or even flawed, which may hamper its use as a proper scientific model.

The complexity of globus: a multidisciplinary perspective.

Globus is a topic of interest for many specialties including otorhinolaryngology, gastroenterology and psychiatry/psychosomatic medicine, but, although many hypotheses have been suggested, key questions about its aetiology remain. This Review provides an overview of the extensive literature concerning this topic and discusses the quality of the evidence to date. Globus has been associated with oropharyngeal structural lesions, upper oesophageal sphincter disorders, oesophageal disorders, GERD, psychosocial factors and psychiatric comorbidity. However, findings are often contradictory and the literature remains highly inconclusive. Indeed, with the exception of patients with structural-based globus, the Rome III criteria for functional globus only apply to a subgroup of patients with idiopathic globus. In clinical reality, there exists a group of patients who present with idiopathic (nonstructural) globus, but nevertheless have dysphagia, odynophagia or GERD-exclusion criteria for globus diagnosis according to Rome III. The symptomatology of patients with globus might be broader than previously thought. It is therefore crucial to approach globus not from one single perspective, but from a multifactorial point of view, with focus on the coexistence and/or interactions of different mechanisms in globus pathogenesis. This approach could be translated to clinical practice by adopting a multidisciplinary method to patients presenting with globus.

A multidimensional model of psychobiological interactions in functional dyspepsia: a structural equation modelling approach.

OBJECTIVE: Gastric sensorimotor function, abuse history, 'trait' and 'state' psychological factors and 'somatisation' all play a role in functional dyspepsia (FD) and its associated impaired quality of life (QoL), but their interplay remains poorly understood. We aimed to test a comprehensive, a priori hypothesised model of interactions between these dimensions in FD. DESIGN: In 259 FD patients, we studied gastric sensitivity with a barostat. We measured abuse history (sexual/physical, childhood/adulthood), 'trait' (alexithymia, trait anxiety) and 'state' (positive/negative affect, depression, panic disorder) psychological factors, somatic symptom reporting (somatic symptom count, dyspepsia, irritable bowel syndrome and fatigue symptoms) and QoL (physical, mental) using validated questionnaires. Confirmatory factor analysis (CFA) was used to assess whether four a priori hypothesised latent variables ('abuse', 'trait affectivity', 'state affect' and 'somatic symptom reporting') were adequately supported by the data. Structural equation modelling (SEM) was used to test the a priori hypothesised relationships between these latent variables and the observed variables gastric sensitivity and QoL. RESULTS: Both the CFA and SEM models fitted the data adequately. Abuse exerted its effect directly on 'somatic symptom reporting', rather than indirectly through psychological factors. A reciprocal relationship between 'somatic symptom reporting' and 'state affect' was found. Gastric sensitivity influences 'somatic symptom reporting' but not vice versa. 'Somatic symptom reporting' and 'trait affectivity' are the main determinants of physical and mental QoL, respectively. CONCLUSIONS: We present the first comprehensive model elucidating the complex interactions between multiple dimensions (gastric sensitivity, abuse history, 'state' and 'trait' psychological factors, somatic symptom reporting and QoL) in FD.