Mickael Bouin

Pain hypersensitivity in patients with functional gastrointestinal disorders: A gastrointestinal-specific defect or a general systemic condition?

Visceral hypersensitivity was shown in patients with functional gastrointestinal disorders (FGID). The mechanisms underlying this sensory dysfunction remain undetermined. The initial hypothesis of a generalized reduction in pain tolerance was rejected by further studies that suggested a normal tolerance to somatic stimuli and led to the generally accepted assumption that pain intolerance is specific and exclusive for visceral stimuli in these patients. We wanted to revisit this theory by examining whether patients with FGID reported perception and tolerance to somatic pain differently from normal subjects and whether the response to somatic pain stimulus was correlated to gastrointestinal symptoms or psychological status or distress. Thirty-three patients with FGID (Rome II criteria)(F/M: 26/7; mean age 48 ± 9.9) and 33 normal controls (F/M: 24/9; mean age 44.1 ± 6.8) were asked to immerse their nondominant hand into 4°C water for as long as possible (maximum 120 sec). Time before appearance of: (1) discomfort, (2) pain, and (3) withdrawing of the hand were noted. The intensity of pain was rated on a visual analog scale from 0 to 100. Self-report questionnaires were used to assess the severity of gastrointestinal symptoms (St-Luc GI index) and the psychological distress (SCL-90) in the patient group. Data are expressed in seconds as mean ± sem. Discomfort sensory thresholds were similar in controls and FGID patients (28 ± 3 and 24 ± 2, respectively; NS) whereas pain and withdrawing were significantly lower in FGID (41 ± 3 and 76 ± 6 sec) than in controls (62 ± 6 and 102 ± 4; P < 0.05). Pain intensity was similar in both groups (64 ± 4 vs 67 ± 3; NS). Female patients showed lower sensory thresholds than male patients and control females (pain thresholds: 39.8 ± 3.4 vs 67.8 ± 16.7 and vs 56.8 ± 8.7; P < 0.05). Sensory thresholds were not different in subgroups of patients with FGID (irritable bowel syndrome and functional dyspepsia). No correlation was shown between sensory thresholds and gastrointestinal index or SCL 90-test. In conclusion, FGID patients showed a threshold to painful somatic stimulus that was lower than in normal subjects. These findings suggest that patients with FGID may have hyperalgesia and low pain tolerance that is not limited to the viscera, but that is part of a systemic general condition.

Widespread hypersensitivity is related to altered pain inhibition processes in irritable bowel syndrome

&NA; The mechanisms of chronic pain in irritable bowel syndrome (IBS) have been widely investigated but remain unclear. The present study investigated the relation between visceral hypersensitivity, cutaneous thermal sensitivity, and central pain mechanisms. Rectal sensitivity was assessed with a barostat, and forearm and calf sensitivity with a contact thermode. Central mechanisms were assessed by counterirritation using sustained cold‐pain to the hand and painful electric shocks to the ankle. Psychological symptoms were also assessed, using questionnaires. Female volunteers with diarrhea‐predominant IBS (n = 27) and healthy controls (n = 25) participated in the study. IBS patients had lower rectal and calf pain thresholds compared to controls (p’s < 0.05). IBS patients also reported more pain than controls for rectal distensions, and heat pain on the calf and forearm (all p’s < 0.001). Cold‐pain inhibited shock‐pain in controls but not IBS patients (controls: −13.5 ± 5.3 vs IBS: +1.9 ± 10.5; p < 0.01). In addition, visceral hypersensitivity was significantly correlated to cutaneous thermal hypersensitivity and pain inhibition deficits, although effects were only weak and moderate, respectively. Furthermore, covariance analyses indicated that psychological factors accounted for group differences in visceral hypersensitivity and pain inhibition deficits. In conclusion, this study confirms the relation between altered pain inhibition processes and widespread hypersensitivity in IBS. The present results also suggests that psychological symptoms and altered pain processing in IBS patients may reflect at least in part, common underlying mechanisms.

Intolerance to visceral distension in functional dyspepsia or irritable bowel syndrome: an organ specific defect or a pan intestinal dysregulation?

Abstract  Functional gastrointestinal disorders (FGID) are characterized by visceral hypersensitivity that could be specific to a region of the gut or reflect a diffuse pan‐intestinal disorder. Sensory thresholds to distension at two visceral sites in patients with different FGIDs were determined. According to Rome II criteria, 30 patients from three groups were studied: patients with (i) functional dyspepsia (FD) or (ii) irritable bowel syndrome (IBS), and (iii) patients with concomitant symptoms of FD and IBS. Pain thresholds to balloon distension were determined in stomach and rectum. In FD patients, gastric intolerance to balloon distension was found in 91% patients; rectal hypersensitivity was documented in 18% patients. In IBS patients, rectal hypersensitivity was seen in 75% patients; while gastric hypersensitivity was never found. In patients with concomitant symptoms of FD + IBS, gastric and rectal intolerance to distension were present respectively in 82 and 91% patients. In the whole group, visceral intolerance to distension was documented at one site in 90% patients and at both sites, i.e. stomach and rectum, in 33% patients. Visceral intolerance to distension can be pan‐intestinal in patients with multiple sites of symptoms, but appears organ‐specific in patients exhibiting a specific site of symptoms.

Decreased pain inhibition in irritable bowel syndrome depends on altered descending modulation and higher-order brain processes

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving abdominal pain and bowel dysfunction. IBS pain symptoms have been hypothesized to depend on peripheral and central mechanisms, but the pathophysiology is still unclear. The aim of the present study was to assess the contribution of cerebral and cerebrospinal processes to pain inhibition deficits in IBS. Fourteen female patients with diarrhea-predominant IBS (IBS-D) and 14 healthy female volunteers were recruited. Acute pain and the nociceptive withdrawal reflex (RIII reflex) were evoked by transcutaneous electrical stimulation of the right sural nerve with modulation by hetero-segmental counter-irritation produced by sustained cold pain applied on the left forearm. Psychological symptoms were assessed by questionnaires. Shock pain decreased significantly during counter-irritation in the controls (P<0.001) but not in IBS patients (P=0.52). Similarly, RIII-reflex amplitude declined during counter-irritation in the controls (P=0.009) but not in IBS patients (P=0.11). Furthermore, pain-related anxiety increased during counter-irritation in IBS patients (P=0.003) but not in the controls (P=0.74). Interestingly, across all subjects, counter-irritation analgesia was positively correlated with RIII-reflex inhibition (r=0.39, P=0.04) and negatively with pain-related anxiety (r=-0.61, P<0.001). In addition, individual differences in counter-irritation analgesia were predicted independently by the modulation of RIII responses (P=0.03) and by pain catastrophizing (P=0.01), with the latter mediating the effect of pain-related anxiety. In conclusion, these results demonstrate that pain inhibition deficits in female IBS-D patients depend on two potentially separable mechanisms reflecting: (1) altered descending modulation and (2) higher-order brain processes underlying regulation of pain and affect.

Biologics in inflammatory bowel disease: what are the data?

Background Over the last decade, biologics have gained an important place for the treatment of moderate to severe inflammatory bowel disease (IBD), and many randomized control trials have evaluated their efficacy. Aim The goal of this review is to analyze the results of these trials and to highlight the evidence and indications emerging from these studies for their implementation in the management of IBD patients. Methods A PubMed search was realized to screen high-quality clinical trials studying biologic agents currently available in clinics for the treatment of IBD. Words used were: “infliximab,” “adalimumab,” “certolizumab,” “golimumab,” “natalizumab,” “vedolizumab,” “ustekinumab,” “azathioprine,” “methotrexate,” “Crohns disease,” and “ulcerative colitis.” Results In Crohns disease, studies supporting induction and maintenance therapies were documented for infliximab, adalimumab, certolizumab, natalizumab, vedolizumab, and ustekinumab. Infliximab, adalimumab, and certolizumab have evidences for fistulizing Crohns disease and only infliximab and adalimumab have evidences for mucosal healing. In ulcerative colitis, studies supporting induction, maintenance, and mucosal healing were found with infliximab, adalimumab, golimumab, and vedolizumab. Only infliximab was associated with evidences for combination therapy with thiopurine and acute severe colitis in ulcerative colitis. Conclusion Management with biologics in IBD patients is well validated by high-quality clinical trials.

Group Counseling Psychotherapy for Patients with Functional Gastrointestinal Disorders: Development of New Measures for Symptom Severity and Quality of Life

Functional gastrointestinal disorders (FGID) can benefit from various psychological interventions. The main objective here was to define the contribution of a new psychotherapeutic intervention, group counseling psychotherapy, for the management of FGID patients. Secondary aims included validation of new measures for gastrointestinal symptoms and quality of life in patients with FGID. Fifty patients seen in a tertiary care center were included in a program of 10 weekly sessions of 2 hr each. Gastrointestinal symptoms, quality of life, and psychological conditions were measured before and after treatment by quantitative indices and by qualitative self-analysis. Gastrointestinal index and quality-of-life index were significantly (P < 0.02) improved at the end of the psychotherapeutic intervention (from 77.5 ± 4.0 to 63.2 ± 4.3 and from 67.7 ± 3.9 to 54.9 ± 3.9, respectively). In a control group of patients observed for a comparable period of time while waiting for the psychotherapy program, gastrointestinal and quality of life indices remained unchanged. The severity of gastrointestinal symptoms and the quality of life deterioration were highly correlated factors (r = 0.8) at entry into the trial, and their improvement with psychotherapy was also correlated (r = 0.6; P < 0.001). Psychological abnormalities were frequent in these patients (anxiety in 31%, somatization in 29%, depression in 26% of the patients). However, no specific disorder could predict the results of the psychotherapeutic intervention. Over the long term (6–24 months after conclusion of treatment), gastrointestinal status, quality of life, and psychological condition were estimated as improved by 53%, 63%, and 67% of the patients, respectively. The gastrointestinal index and quality of life index we developed were validated to detect the disease and to follow its evolution in response to treatment. In conclusion, group counseling psychotherapy offered a significant contribution for the management, improving gastrointestinal symptoms and quality of life, of FGID patients. New measures for symptom severity and quality of life are available.

Cardiac sources of embolism should be routinely screened in ischemic colitis

OBJECTIVES:Potential cardiac sources of embolism may promote ischemic colitis. The aim of this study was to evaluate their role in segmental, nongangrenous ischemic colitis and to determine the usefulness of routine cardiac evaluation in patients with this disease.METHODS:Sixty case and 60 control patients matched for age and gender were included and questioned regarding treatment and prior cardiovascular history or risk factors. Potential cardiac sources of embolism, classified as “proven” or “still debated,” were screened using an electrocardiogram, rhythmic Holter monitoring over 24 h, and transthoracic echocardiography.RESULTS:Sex ratio (male:female) was 1:2, and mean age was 70 ± 14 yr. Case and control patients had similar drug use, prior cardiovascular history, and risk factors. A potential cardiac source of embolism was found in 26/60 case (43%), compared with 14/60 control patients (23%) (p = 0.02; OR = 2.5, 95% CI = 1.2–5.5). Excluding the “still debated,” 21/60 case (35%), compared with 8/60 control patients (13%), had a “proven” cardiac source of embolism (p < 0.01; OR = 3.5, 95% CI = 1.4–8.4). Electrocardiogram alone misdiagnosed 72% of the “proven” cardiac sources of embolism, whereas the combination electrocardiogram plus Holter monitoring detected 71%, and electrocardiogram plus echocardiography 62%. Twelve of 21 case patients with at least one proven cardiac source of embolism, were previously unknown. Anticoagulant therapy was required in 32% of case patients and antiarrhythmic therapy in 25% of cases.CONCLUSIONS:Potential cardiac sources of embolism were more common in patients with segmental, nongangrenous ischemic colitis than in control patients. Therefore, these patients should undergo a routine electrocardiogram, rhythmic Holter monitoring, and transthoracic echocardiography. Anticoagulant therapy should also be considered for this patient population.

Thicker Posterior Insula Is Associated With Disease Duration in Women With Irritable Bowel Syndrome (IBS) Whereas Thicker Orbitofrontal Cortex Predicts Reduced Pain Inhibition in Both IBS Patients and Controls

UNLABELLED Patients with irritable bowel syndrome (IBS) are affected by chronic abdominal pain and show decreased pain inhibition. Moreover, they exhibit differences in brain morphology compared with healthy volunteers. The aim of this study was to examine whether decreased pain inhibition is associated with altered brain morphology in IBS patients. Structural magnetic resonance imaging scans were acquired in 14 female patients with diarrhea-predominant IBS and 14 controls. Pain and anxiety modulation were characterized using electrical stimulation of the sural nerve and heterotopic noxious counterstimulation. IBS patients reported decreased pain inhibition (P = .02) as well as increased shock anxiety, pain catastrophizing, depressive symptoms, and trait anxiety (Ps ≤ .05). IBS patients also showed a thicker right posterior insula (pINS), associated with longer IBS duration (r = .67, P = .02). In addition, thicker right lateral orbitofrontal cortex was strongly associated with less pain inhibition in both IBS patients (r = .70, P = .02) and controls (r = .68, P = .01). Results are consistent with the role of the insula in interoception and pain and suggest that IBS may induce thickening of the pINS. Reduced pain inhibition may further involve a modification of the regulatory influence of the orbitofrontal cortex on pain-related processes. PERSPECTIVE This study investigated the brain morphology of IBS patients. IBS patients showed thicker right pINS, associated with longer disease duration but not with psychological symptoms. This suggests that IBS induces thickening of pINS, which may contribute to its pathophysiology, consistent with the role of the pINS in interoception and pain.

Prevalence of Electrocardiographic and Echocardiographic Abnormalities in Ambulatory Ischemic Colitis

The aim of this study was to evaluate the prevalence of cardiac arrhythmia and intracardiac embolic process in ambulatory ischemic colitis. From November 1994 to November 1997, 33 consecutive cases of ambulatory ischemic colitis were detected. This study included 21 women and 12 men with a mean age of 71 years. All patients underwent a cardiovascular investigation including questioning, electrocardiogram, 24-hr ambulatory electrocardiography and transthoracic echocardiography. A prior history of ischemic colitis was found in four cases (12%). Cardiac arrhythmia was detected in eight cases. Transthoracic echocardiography showed an intracardiac process, potentially responsible for a peripheral embolism, in four cases. In conclusion, the aggregate, in 33% of the patients, there was potential cardiac etiology. This suggests that when ambulatory ischemic colitis occurs, it is necessary to perform an exhaustive cardiovascular evaluation similar to those performed in other ischemic diseases.

IgG4-Related Esophageal Disease Presenting as Esophagitis Dissecans Superficialis With Chronic Strictures.

IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmocytic infiltrate of IgG4-positive cells, storiform fibrosis and can be associated with tumefactive lesions. IgG4-related disease involving the upper gastrointestinal tract is rare and only two previous case reports have reported IgG4-related esophageal disease. We report the case of a 63-year-old female patient with a long-standing history of severe dysphagia and odynophagia with an initial diagnosis of reflux esophagitis. Symptoms persisted despite anti-acid therapy and control esophagogastroduodenoscopy (EGD) revealed endoscopic images consistent with esophagitis dissecans superficialis (sloughing esophagitis). An underlying autoimmune process was suspected and immunosuppressant agents were tried to control her disease. The patient eventually developed disabling dysphagia secondary to multiple chronic esophageal strictures. A diagnosis of IgG4-related disease was eventually made after reviewing esophageal biopsies and performing an immunohistochemical study with an anti-IgG4 antibody. Treatment attempts with corticosteroids and rituximab was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. Our case report describes this unique case of IgG4-related esophageal disease presenting as chronic esophagitis dissecans with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease.