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Background: Patients (20%-50%) with inflammatory bowel disease (IBD) experience chronic abdominal pain during remission. The clinical features of IBD patients with abdominal pain during remission remain poorly characterized. This cross-sectional pilot study aimed to assess patient recruitment, adherence, and feedback to optimize questionnaires for future use and to determine the clinical features that distinguish IBD patients in remission with and without abdominal pain., Methods: Online validated questionnaires about disease activity, symptoms, and psychological factors were sent to participants of the UK National Institute for Health and Care Research (NIHR) IBD BioResource, which is a national research platform consisting of re-callable IBD patients designed to expedite research into Crohn's and colitis. Inclusion/exclusion criteria of the IBD BioResource main cohort were applied. Descriptive and inferential statistics were applied to participants in remission. p-values ≤0.01 were considered significant., Key Results: A total of 2050 patients were approached; 291 (14.2%) of these agreed to participate. In 35 patients, technical problems, length, and poor understanding of the relevance of some questionnaires affected completion as confirmed by feedback. In total, 244 patients were full responders with 122 (50%) in remission; 33 (27%) of these had chronic abdominal pain. Comparison of those with versus without (n = 89) chronic abdominal pain yielded higher scores in patients with pain for the following: somatization (p < 0.001); gastrointestinal symptoms rating scale score (p = <0.001); highly sensitive person scale (p = 0.007); catastrophizing score (p = 0.010). Trends were observed for azathioprine use (p = 0.021); coping resources inventory health in general (p = 0.046); neuroticism (p = 0.019); and poor sleep (p = 0.03)., Conclusions & Inferences: Differences in symptoms and psychological characteristics exist between IBD patients in remission with and without abdominal pain. Confirmation of findings in larger studies may facilitate development of personalized chronic pain treatments for IBD patients., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Joint hypermobility (JH) is associated with autonomic nervous system dysregulation and functional abdominal pain disorders (FAPDs). Understanding the neurophysiological processes linking these conditions can inform clinical interventions. Autonomic activity regulates gastrointestinal (GI) sensorimotor function and may be a key mechanism. The aims of this study were to examine the relation of JH with dynamic autonomic activity and parasympathetic regulation in adolescents with FAPDs and identify optimal JH cutoff scores that best index autonomic regulation in FAPDs., Methods: A total of 92 adolescents with FAPDs and 27 healthy controls (age 8-18 years; 80% female) were prospectively enrolled. JH was assessed by Beighton scores. ECG recordings were conducted during supine, sitting, and standing posture challenges. ECG-derived variables-heart period (HP), respiratory sinus arrhythmia (RSA), and vagal efficiency (VE)-were analyzed using linear regression and mixed effects modeling., Key Results: Beighton scores of ≥4 optimally distinguished autonomic function. Adolescents with FAPD and JH had reduced VE compared to adolescents with FAPDs without JH (B = 18.88, SE = 6.25, p = 0.003) and healthy controls (B = 17.56, SE = 8.63, p = 0.044). These subjects also had lower and less dynamic RSA and HP values during posture shifts, with strongest differences in supine position and using the VE metric., Conclusions & Inferences: Suboptimal autonomic regulation indexed by reduced vagal efficiency may be a mechanism of symptoms in hypermobile FAPD patients with Beighton score ≥ 4. Autonomic disturbance may serve as potential intervention target for patients with JH and functional GI disorders., (© 2021 John Wiley & Sons Ltd.)

Introduction: Chronic constipation is classified into 2 main syndromes, irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), on the assumption that they differ along multiple clinical characteristics and are plausibly of distinct pathophysiology. Our aim was to test this assumption by applying machine learning to a large prospective cohort of comprehensively phenotyped patients with constipation., Methods: Demographics, validated symptom and quality of life questionnaires, clinical examination findings, stool transit, and diagnosis were collected in 768 patients with chronic constipation from a tertiary center. We used machine learning to compare the accuracy of diagnostic models for IBS-C and FC based on single differentiating features such as abdominal pain (a "unisymptomatic" model) vs multiple features encompassing a range of symptoms, examination findings and investigations (a "syndromic" model) to assess the grounds for the syndromic segregation of IBS-C and FC in a statistically formalized way., Results: Unisymptomatic models of abdominal pain distinguished between IBS-C and FC cohorts near perfectly (area under the curve 0.97). Syndromic models did not significantly increase diagnostic accuracy (P > 0.15). Furthermore, syndromic models from which abdominal pain was omitted performed at chance-level (area under the curve 0.56). Statistical clustering of clinical characteristics showed no structure relatable to diagnosis, but a syndromic segregation of 18 features differentiating patients by impact of constipation on daily life., Discussion: IBS-C and FC differ only about the presence of abdominal pain, arguably a self-fulfilling difference given that abdominal pain inherently distinguishes the 2 in current diagnostic criteria. This suggests that they are not distinct syndromes but a single syndrome varying along one clinical dimension. An alternative syndromic segregation is identified, which needs evaluation in community-based cohorts. These results have implications for patient recruitment into clinical trials, future disease classifications, and management guidelines., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method., Methods: Thirty-seven patients with IBS (26 women; mean age 36.7 years) and 36 healthy controls (HC; 24 women; mean age 31.1 years) completed an electronic ESM during 7 consecutive days. Abdominal pain and stress were scored on an 11-point Numeric Rating Scale at a maximum of 10 random moments each day., Results: Abdominal pain scores were 2.21 points higher in patients with IBS compared with those in HC (P < 0.001), whereas stress levels did not differ significantly (B: 0.250, P = 0.406). In IBS, a 1-point increase in stress was associated with, on average, 0.10 points increase in abdominal pain (P = 0.017). In HC, this was only 0.02 (P = 0.002). Stress levels at t = -1 were not a significant predictor for abdominal pain at t = 0 in both groups, and vice versa., Discussion: Our results demonstrate a positive association between real-time stress and abdominal pain scores and indicate a difference in response to stress and not a difference in experienced stress per se. Furthermore, an in-the-moment rather than a longitudinal association is suggested. This study underlines the importance of considering the individual flow of daily life and supports the use of real-time measurement when interpreting potential influencers of abdominal symptoms in IBS.

Background: Irritable bowel syndrome (IBS) is common and is characterised by recurrent abdominal pain, which is a major contributor to healthcare seeking. The neurobiological basis of this pain is incompletely understood. Conditioned pain modulation is a neuromodulatory mechanism through which the brain inhibits the nociceptive afferent barrage through the descending pathways. Reduced conditioned pain modulation has been implicated in the pathophysiology of IBS, although to date only in studies with relatively small sample sizes., Aim: To clarify the relationship between conditioned pain modulation and IBS by undertaking a systemic review and meta-analysis METHODS: A systematic review of MEDLINE and Web of Science databases was searched (up to 10 May 2018). We included studies examining conditioned pain modulation in adults with IBS and healthy subjects. Data were pooled for meta-analysis to calculate the odds ratio and effect size of abnormal conditioned pain modulation in IBS, with 95% confidence intervals (CI)., Results: The search strategy identified 645 studies, of which 13 were relevant and 12 met the inclusion criteria. Conditioned pain modulation in IBS patients vs healthy subjects was significantly reduced, odds ratio 4.84 (95% CI: 2.19-10.71, P < 0.0001), Hedges' g effect size of 0.85 (95% CI: 0.42-1.28, P < 0.001). There was significant heterogeneity in effect sizes (Q-test χ 2 = 52, P < 0.001, I 2 = 78.8%) in the absence of publication bias., Conclusion: Conditioned pain modulation is significantly diminished in patients with IBS vs healthy controls. These data suggest that abnormal descending pathways may play an important pathophysiological role in IBS, which could represent an investigation and a therapeutic target in IBS., (© 2018 John Wiley & Sons Ltd.)

Narcotic bowel syndrome is characterised by worsening abdominal pain in the context of escalating or continuous opioid therapy. Although narcotic bowel syndrome is rarely diagnosed, given the current epidemic of opioid use, it is likely to be under-recognised. The underlying pathophysiological mechanisms of narcotic bowel syndrome are incompletely understood; however, opioid-induced hyperalgesia is likely to be a central facet. The putative mechanisms of hyperalgesia include activation of bimodal opioid regulatory systems, counter-regulatory mechanisms, neuroinflammation, opioid facilitation, and interactions of the N-methyl D-aspartate receptor with opioids at the level of the spinal cord. The cornerstone of management is the development of a therapeutic alliance with the patient, education of the patient as to the mechanisms by which opioids might paradoxically worsen pain, and implementation of an opioid detoxification programme. Opioid detoxification regimens vary between centres, but frequently include tapering or substitution of opioids and concomitant co-administration of antidepressants, anxiolytics, and psychological therapies. Despite these interventions, recidivism rates remain high. Further prospective research is warranted to determine the epidemiology of narcotic bowel syndrome and delineate the most efficacious detoxification programmes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Consensus on standard methods to assess chronic abdominal pain in patients with irritable bowel syndrome (IBS) is currently lacking., Aim: To systematically review the literature with respect to instruments of measurement of chronic abdominal pain in IBS patients., Methods: Systematic literature search was performed in PubMed/Medline databases for studies using pain measurement instruments in patients with IBS., Results: One hundred and ten publications were reviewed. A multitude of different instruments is currently used to assess chronic abdominal pain in IBS patients. The single-item methods, e.g. the validated 10-point numeric rating scale (NRS), and questionnaires assessing gastrointestinal symptoms severity, focus mostly on the assessment of only the intensity of abdominal pain. Of these questionnaires, the validated IBS-Symptom Severity Scale includes the broadest measurement of pain-related aspects. General pain questionnaires and electronic momentary symptom assessment tools have been used to study abdominal pain in IBS patients, but have not yet been validated for this purpose. The evidence for the use of provocation tests, e.g. the rectal barostat with balloon distention, for measurement of abdominal pain in IBS is weak, due to the poor correlation between visceral pain thresholds assessed by provocation tests and abdominal pain as assessed by retrospective questionnaires., Conclusions: The multitude of different instruments to measure chronic abdominal pain in IBS makes it difficult to compare endpoints of published studies. There is need for validated instruments to assess chronic abdominal pain in IBS patients, that overcome the limitations of the currently available methods., (© 2015 John Wiley & Sons Ltd.)

Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. Patient education directed towards an explanation of the pathophysiology of functional abdominal pain is in our opinion a prerequisite step and provides the rationale for the introduction of interventions. Interventions can usefully be categorised into general measures, pharmacotherapy, psychological interventions and 'step-up' treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids. Psychological treatments include cognitive behavioural therapy and hypnotherapy. However, the objective evidence base for these interventions is largely derived from other chronic pain syndrome, and further research is warranted in adult patients with functional abdominal pain., (© The Royal Society of Medicine.)

Purpose of Review: Chronic visceral pain is one of the most common causes of morbidity in the general population. Despite a gargantuan effort from academia and the pharmaceutical industry, an integrated understanding of the pathophysiological mechanisms of chronic visceral pain, particularly with respect to functional gastrointestinal disorders, remains incomplete., Recent Findings: Advances in our understanding of the structure and function of the microanatomy of nociception has led to the identification of a number of ion channels, neurotransmitter receptors and trophic factors that may be intimately involved in chronic visceral pain. These advances have been paralleled with those in the fields of genetics, neurophysiology and functional neuroimaging. These advances have allowed the objective assessment of central processing of visceral sensation and furthermore the factors that may modulate this process in health and disease., Summary: These findings have important implications for the future direction of research. The real challenge for the future progress is to further characterize patients with chronic visceral pain in terms of their clinical phenotype, genotyping and nociceptive physiology on an individual basis towards the development of more efficacious therapeutic strategies.

Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogeneous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.

Evidence from both human and animal studies has demonstrated a key role for brainstem centers in the control of ascending nociceptive input. Nuclei such as the rostral ventromedial medulla and periaqueductal gray (PAG) are able to both inhibit and facilitate the nociceptive response. It has been proposed that altered descending modulation may underlie many of the chronic pain syndromes (both somatic and visceral). We used functional magnetic resonance imaging to image the neural correlates of visceral and somatic pain within the brainstem. Ten healthy subjects were scanned twice at 3 tesla, during which they received matched, moderately painful, electrical stimuli to either the midline lower abdomen or rectum. Significant activation was observed in regions consistent with the PAG, nucleus cuneiformis (NCF), ventral tegmental area/substantia nigra, parabrachial nuclei/nucleus ceruleus, and red nucleus bilaterally to both stimuli. Marked spatial similarities in activation were observed for visceral and somatic pain, although significantly greater activation of the NCF (left NCF, p = 0.02; right NCF, p = 0.01; Student's paired t test, two-tailed) was observed in the visceral pain group compared with the somatic group. Right PAG activity correlated with anxiety during visceral stimulation (r = 0.74; p < 0.05, Pearson's r, two-tailed) but not somatic stimulation. We propose that the differences in NCF and right PAG activation observed may represent a greater nocifensive response and greater emotive salience of visceral over somatic pain.

Functional abdominal pain or functional abdominal pain syndrome (FAPS) is an uncommon functional gut disorder characterised by chronic or recurrent abdominal pain attributed to the gut but poorly related to gut function. It is associated with abnormal illness behaviour and patients show psychological morbidity that is often minimised or denied in an attempt to discover an organic cause for symptoms. Thus the conventional biomedical approach to the management of such patients is unhelpful and a person's symptom experience is more usefully investigated using a biopsychosocial evaluation, which necessarily entails a multidisciplinary system of healthcare provision. Currently the pathophysiology of the disorder is poorly understood but is most likely to involve a dysfunction of central pain mechanisms either in terms of attentional bias, for example, hypervigilance or a failure of central pain modulation/inhibition. Although modern neurophysiological investigation of patients is promising and may provide important insights into the pathophysiology of FAPS, current clinical management relies on an effective physician-patient relationship in which limits on clinical investigation are set and achievable treatment goals tailored to the patient's needs are pursued.

Background and Aims: This study assessed whether childhood and current adversities: (a) were more prevalent in patients with functional dyspepsia (FD) or non-cardiac chest pain (NCCP) than in patients with gastro-oesophageal reflux disease (GORD) or ischaemic heart disease (IHD); and (b) predicted health related quality of life in these disorders., Patients: Cohort study of consecutive attenders to gastroenterology and cardiology clinics in a secondary/tertiary referral centre., Methods: Patients were interviewed using the childhood experience of care and abuse and life events and difficulties schedules. Distress was assessed by questionnaire. Outcome was assessed using SF36 at the index clinic visit and six months later., Results: A total of 133 patients were included (40 NCCP, 43 FD, 29 GORD, and 21 IHD) (67% response rate). The diagnostic groups did not differ significantly in the proportion reporting childhood adversity (30%), ongoing social stress (40%), lack of a close confidant (14%), or level of psychological distress. Reported childhood adversity was associated with poor outcome at the index visit (SF36 physical component score: 36.6 (SEM 1.8) v 42.3 (SEM 1.2) for the remainder; p = 0.014). In multiple regression analysis, childhood adversity was a significant independent predictor for patients with functional disorders (NCCP and FD) but not organic disorders (GORD or IHD). Change in SF36 score at six months was determined by age and distress score at the index visit in both groups., Conclusion: Childhood adversity was common among this consecutive sample but was associated directly with poor outcome only in patients with functional gastrointestinal syndromes. Distress is an important predictor of outcome in all patients. Greatest impairment occurs when lack of social support accompanies reported childhood adversity.

Objective: A comprehensive model of health care use by patients with functional gastrointestinal disorders has not been fully tested. This study aimed to establish whether reported childhood and/or recent adversity are independent predictors of health care use when all other relevant factors are also included in the model., Materials and Methods: Consecutive new patients with upper abdominal or chest pain presenting to a secondary/tertiary clinic were assessed using the Childhood Experience of Care and Abuse and Life Events and Difficulties Schedules. They completed the Hospital Anxiety and Depression and Health Anxiety Questionnaires. Outcome was total number of health care visits recorded in hospital and general practice (GP) records over 18 months., Results: One hundred fifty-one patients were included (65% response rate). Health care visits were most frequent in unmarried (p < 0.0005), females (p < 0.0005), and those lacking social support (p = 0.012). In multiple regression analysis to predict number of health care visits, reported sexual abuse (p = 0.042) and death of a sibling during childhood (p = 0.026) were also independent predictors, together with SF36 subscale scores for physical function, health perception, and mental health (35% of variance explained). Childhood adversity predicted health care use in patients with functional gastrointestinal disorders and recent social stress did so in patients with demonstrated pathological findings., Conclusion: After adjustment for demographic, physical, and psychological factors, childhood adversity, especially in severe form, is an independent predictor of health care use in patients with upper functional gastrointestinal disorders. The same was not true for patients consulting for demonstrable pathological abnormalities, for whom ongoing social stress was an independent predictor.

Abdominal pain occurs commonly in irritable bowel syndrome. The mechanism of pain is likely to be either peripheral or central sensitization of gut nerves or aberrant brain processing. Functional brain techniques are now allowing the study of brain-gut interactions.

Abstract: Background: End‐of‐day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient‐reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross‐cultural adaptation. Methods: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward‐and‐back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients’ understanding with the final items. Key results: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. Conclusions and Inferences: An ESM‐based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross‐cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow. [ABSTRACT FROM AUTHOR]