Factors influencing rectal hypersensitivity in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: A frequent, although not universal, feature of irritable bowel syndrome (IBS) is heightened sensitivity to mechanical stimulation of the rectum, termed rectal hypersensitivity (RH). Differences in RH-based on sex, IBS subtype, IBS diagnostic criteria and age of population studied are incompletely understood. We aimed to determine whether IBS population had lower pain thresholds than healthy controls. METHODS: We searched MEDLINE and EMBASE databases (1970-2021). Prospective studies that compared pain/discomfort thresholds to mechanical rectal stimuli in IBS and healthy controls were included. Data were pooled for meta-analyses and effect sizes were calculated with 95% confidence interval (CIs). RESULTS: Our search strategy identified 809 studies of which 32 studies met the inclusion criteria. Reduced rectal pain thresholds was more common in IBS patients compared to healthy controls with an effect size of 1.00 95% CIs (0.77-1.24) (p < 0.0001) (I2  = 78.6%). The pediatric IBS population had lower pain thresholds than adult IBS populations (p = 0.05) but no difference based on IBS diagnostic criteria, subtype or sex. CONCLUSION & INFERENCES: The results suggest that reduced rectal pain threshold to experimental stimulation is far more common in IBS patients than healthy controls. Further research is required to understand the pathophysiological and therapeutic implications of rectal sensitivity such as its role in measuring response to treatment and prognosis in IBS.

Rectal Hypersensitivity in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Abdominal pain is a key symptom of inflammatory bowel disease (IBD), particularly in active IBD, but also occurs in patients with quiescent disease suggesting that mechanisms other than active inflammation may be responsible. Putative hypothesis to explain chronic abdominal pain in patients with quiescent IBD includes crossover with irritable bowel syndrome where rectal hypersensitivity is common and has pathophysiological implications. In contrast, in IBD, the role of rectal hypersensitivity has not been established. We aimed to determine if rectal hypersensitivity was more common in IBD compared to a healthy control population. We searched MEDLINE and EMBASE databases (1970-2018). Prospective studies that measured pain/discomfort thresholds to mechanical rectal stimuli in IBD and healthy controls were included. Data were pooled for meta-analysis and effect sizes were calculated with 95% confidence intervals (CIs). Our search strategy identified 222 citations of which 8 met the inclusion criteria, covering 133 individuals with IBD (67 men), aged between 10 and 77 compared to 99 healthy controls (55 men), aged between 10 and 67. The prevalence of rectal hypersensitivity in IBD compared to healthy controls was similar with an effect size of 0.59 (95% CIs: -0.27 to 1.44, P = .16, I 2 = 87.3%). Subgroup analysis did show a significant effect size for patients compared to healthy controls with active disease (1.32) but not for quiescent disease (-0.02). These results suggest that reduced rectal pain thresholds to experimental stimulation are not seen in IBD populations except during active flares of the disease. Further research is required to understand the pathophysiology of chronic abdominal pain in quiescent IBD populations with and without chronic abdominal pain to identify appropriate management strategies.

Transcutaneous vagus nerve stimulation prevents the development of, and reverses, established oesophageal pain hypersensitivity.

BACKGROUND: The vagus nerve exerts an anti-nociceptive effect on the viscera. AIM: To investigate whether transcutaneous vagal nerve stimulation (t-VNS) prevents the development of and/or reverses established visceral hypersensitivity in a validated model of acid-induced oesophageal pain. METHODS: Before and after a 30-minute infusion of 0.15M hydrochloric acid into the distal oesophagus, pain thresholds to electrical stimulation were determined in the proximal non-acid exposed oesophagus. Validated sympathetic (cardiac sympathetic index) and parasympathetic (cardiac vagal tone [CVT]) nervous system measures were recorded. In study 1, 15 healthy participants were randomised in a blinded crossover design to receive either t-VNS or sham for 30 minutes during acid infusion. In study 2, 18 different healthy participants were randomised in a blinded crossover design to receive either t-VNS or sham, for 30 minutes after acid infusion. RESULTS: Study 1: t-VNS increased CVT (31.6% ± 58.7 vs -9.6 ± 20.6, P = 0.02) in comparison to sham with no effect on cardiac sympathetic index. The development of acid-induced oesophageal hypersensitivity was prevented with t-VNS in comparison to sham (15.5 mA per unit time (95% CI 4.9 - 26.2), P = 0.004). Study 2: t-VNS increased CVT (26.3% ± 32.7 vs 3 ± 27.1, P = 0.03) in comparison to sham with no effect on cardiac sympathetic index. t-VNS reversed established acid-induced oesophageal hypersensitivity in comparison to sham (17.3mA/unit time (95% CI 9.8-24.7), P = 0.0001). CONCLUSIONS: t-VNS prevents the development of, and reverses established, acid-induced oesophageal hypersensitivity. These results have therapeutic implications for the management of visceral pain hypersensitivity.

How the Internet influences the relationship between outpatients and gastroenterologists: A multicenter study.

BACKGROUND/AIMS: The Internet offers a lot of non-filtered medical information which may interfere with the patient-doctor relationship. The aim of the present study was to assess the influence of the Internet on the classical doctor-patient relationship in gastroenterological outpatient settings. MATERIALS AND METHODS: A multicenter study was conducted, including a representative sample selected from five major regional medical centers throughout Romania. We designed a questionnaire which had two parts. One had to be filled out by adult patients on their first visit to a gastroenterology clinic and the other by physicians, stating the diagnosis and giving a doctor-patient collaboration score. RESULTS: From a total of 485 patients (49.9% females, mean age 50.42 years), 64.9% had Internet access, 75% out of whom searched for their symptoms online. University graduates searched for their symptoms online more often than secondary school graduates (80% vs. 31.1%, p<0.05). Most patients stated that they used the Internet to identify the most appropriate medical specialist for their condition. Internet users were less likely to visit a general practitioner (GP) before coming to a specialist (85.3% vs. 92.2%, odds ratio (OR) 0.491, 95% confidence interval (CI) 0.24-0.98, p<0.05). Patients who had searched for their symptoms online were less likely to follow the treatment prescribed by the GP (53.6% vs. 67.5%, p=0.004), but they received a better collaboration score (OR 1.12, 95% CI 1.05-1.36, p<0.05). CONCLUSION: The Internet exerts a positive influence on specialist doctor-patient relationship, but it might burden the health system with the incorrect tendency to replace the role of the GP.

The anatomical basis for transcutaneous auricular vagus nerve stimulation.

The array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation (VNS) being explored as a management option in a number of clinical disorders, such as heart failure, migraine and inflammatory bowel disease. Both invasive (surgically implanted) and non-invasive (transcutaneous) techniques of VNS exist. Transcutaneous VNS (tVNS) delivery systems rely on the cutaneous distribution of vagal afferents, either at the external ear (auricular branch of the vagus nerve) or at the neck (cervical branch of the vagus nerve), thus obviating the need for surgical implantation of a VNS delivery device and facilitating further investigations across a wide range of uses. The concept of electrically stimulating the auricular branch of the vagus nerve (ABVN), which provides somatosensory innervation to several aspects of the external ear, is relatively more recent compared with cervical VNS; thus, there is a relative paucity of literature surrounding its operation and functionality. Despite the increasing body of research exploring the therapeutic uses of auricular transcutaneous VNS (tVNS), a comprehensive review of the cutaneous, intracranial and central distribution of ABVN fibres has not been conducted to date. A review of the literature exploring the neuroanatomical basis of this neuromodulatory therapy is therefore timely. Our review article explores the neuroanatomy of the ABVN with reference to (1) clinical surveys examining Arnold's reflex, (2) cadaveric studies, (3) fMRI studies, (4) electrophysiological studies, (5) acupuncture studies, (6) retrograde tracing studies and (7) studies measuring changes in autonomic (cardiovascular) parameters in response to auricular tVNS. We also provide an overview of the fibre composition of the ABVN and the effects of auricular tVNS on the central nervous system. Cadaveric studies, of which a limited number exist in the literature, would be the 'gold-standard' approach to studying the cutaneous map of the ABVN; thus, there is a need for more such studies to be conducted. Functional magnetic resonance imaging (fMRI) represents a useful surrogate modality for discerning the auricular sites most likely innervated by the ABVN and the most promising locations for auricular tVNS. However, given the heterogeneity in the results of such investigations and the various limitations of using fMRI, the current literature lacks a clear consensus on the auricular sites that are most densely innervated by the ABVN and whether the brain regions secondarily activated by electrical auricular tVNS depend on specific parameters. At present, it is reasonable to surmise that the concha and inner tragus are suitable locations for vagal modulation. Given the therapeutic potential of auricular tVNS, there remains a need for the cutaneous map of the ABVN to be further refined and the effects of various stimulation parameters and stimulation sites to be determined.

Management of supragastric belching with cognitive behavioural therapy: factors determining success and follow-up outcomes at 6-12 months post-therapy.

BACKGROUND: Supragastric belching (SGB) has a significant behavioural component. We recently used cognitive behavioural therapy (CBT) to treat SGB. We demonstrated that CBT significantly reduces symptoms and improves quality of life in 50% of patients who had completed treatment. AIMS: To investigate factors associated with successful CBT for SGB and to assess symptoms 6-12 months after completion of CBT METHODS: Records of 39 patients who had completed the CBT protocol were analysed. Per cent pre- to post-treatment change in symptoms was assessed using a visual analogue scale (VAS) score. We evaluated the association between 'pre-treatment' factors and 'during-treatment' factors, and symptomatic outcomes. Symptoms were also assessed 6-12 months after treatment. RESULTS: From 'pre-treatment factors', a lower number of SGBs (P < .01) and lower hypervigilance score (P < .04) were significantly associated with a better outcome. From 'during-treatment factors' a higher CBT 'proficiency score' ([a] acceptance of the explanation that SGB is a behavioural phenomenon [b] detection of a warning signal before belching [c] adherence to the exercises treatment) was associated with a better outcome (P = .001). Multiple regression analysis found that number of SGBs, hypervigilance score and CBT proficiency score were independently associated with outcome (P < .01, P = .01, P < .01). VAS score before CBT (267 ± 79) decreased to 151 ± 88 soon after CBT (P < .001), and the effect persisted at 6-12 months follow-up (153 ± 82). CONCLUSIONS: Lower number of SGBs, lower hypervigilance score and higher proficiency during CBT were associated with better CBT outcome. CBT positive effect lasted for at least 6-12 months post-treatment.

Systematic review with meta-analysis: conditioned pain modulation in patients with the irritable bowel syndrome.

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 χ2 = 52, P < 0.001, I2 = 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.