Characterization of autonomic dysfunction in patients with irritable bowel syndrome using fingertip blood flow

Abstract  Fingertip blood flow (FTBF) as measured by laser Doppler flowmetry (LDF) measurement is considered an indicator of sympathetic nerve function. We evaluated autonomic function in patients with irritable bowel syndrome (IBS) by assessing FTBF with both LDF and continuous-wave (cw) Doppler sonography. Firstly, the two methods were compared in 40 healthy volunteers. Next, 59 patients with IBS as well as 118 healthy volunteer controls were studied. In the supine position, FTBF in the right index finger was measured with cw Doppler sonography, whereas FTBF in the left index finger was assessed with LDF. After baseline measurement for at least 5 min, the volunteers received sympathetic stimulation from cold stress applied without notification in the form of an icebag (0 °C) upon the left forearm for 1 min. The new cw Doppler sonography method can be used in place of the old LDF method for clinical purposes. FTBF velocity before stimulation ( V _pre) was significantly lower in the IBS group than that in the healthy volunteers ( P  < 0.01). In addition, the time required for FTBF to return to V _pre after stimulation was significantly longer in the IBS group than that in the control group. ( P  = 0.02). Thus, measurement of FTBF with cw Doppler sonography can be useful in the assessment of sympathetic nerve function. The IBS patients showed an abnormal FTBF response suggesting the presence of excess sympathetic activity.     

Vagal dysfunction in irritable bowel syndrome assessed by rectal distension and baroreceptor sensitivity

Abstract Autonomic nervous system dysfunction has been implicated in the pathophysiology of irritable bowel syndrome (IBS). This study characterized the autonomic response to rectal distension in IBS using baroreceptor sensitivity (BRS), a measure of autonomic function. Rectal bag pressure, discomfort, pain, ECG, blood pressure and BRS were continuously measured before, during and after rectal distension in 98 healthy volunteers (34 ± 12 years old, 52 females) and 39 IBS patients (39 ± 11 years old, 35 females). In comparison with the healthy volunteers, IBS patients experienced significantly more discomfort (69 ± 2.2% vs 56 ± 3.6%; P < 0.05), but not pain (9 ± 1.4% vs 6 ± 2.4%; ns) with rectal distension despite similar distension pressures (51 ± 1.4 vs 54 ± 2.4 mmHg; ns) and volumes (394 ± 10.9 vs 398 ± 21.5 mL; ns). With rectal distension, heart rate increased in both healthy volunteers (66 ± 1 to 71 ± 1 bpm; P < 0.05) and IBS patients (66 ± 2 to 74 ± 3 bpm; P < 0.05). Systolic blood pressure also increased in both healthy volunteers (121 ± 2 to 143 ± 2 mmHg; P < 0.05) and patients (126 ± 3 to 153 ± 4 mmHg (P < 0.05) as did diastolic blood pressure, 66 ± 2 to 80 ± 2 mmHg (P < 0.05), compared with 68 ± 3 to 84 ± 3 mmHg (P < 0.05) in IBS patients. The systolic blood pressure increase observed in IBS patients was greater than that seen in healthy volunteers and remained elevated in the post distension period (139 ± 3 mmHg vs 129 ± 2 mmHg; P < 0.05). IBS patients had lower BRS (7.85 ± 0.4 ms mmHg^?1) compared with healthy volunteers (9.4 ± 0.3; P < 0.05) at rest and throughout rectal distension. Greater systolic blood pressure response to rectal distension and associated diminished BRS suggests a compromise of the autonomic nervous system in IBS patients.     

Heart rate variability is related to pain severity and predominant bowel pattern in women with irritable bowel syndrome

This study examined heart rate variability (HRV) in women with irritable bowel syndrome (IBS) to determine its association with gut pain and predominant bowel pattern. Women with IBS (constipation predominant n = 45, diarrhoea predominant n = 64, alternating n = 56) and healthy controls (n = 50) were recruited from the community. Severity of gut pain was measured retrospectively. The HRV (24 h) was summarized as high-frequency (HF) power and the ratio of low-frequency (LF) power to HF power. Among those women with IBS who have severe gut pain, the 15 constipation-predominant women had lower (P = 0.01) HF power and higher (P = 0.003) LF/HF ratio (geometric means 70 and 7.5, respectively) than the 21 women with diarrhoea-predominant IBS (286 and 3.1) and controls (224 and 3.9). In contrast, among women without severe pain, there is a smaller and not quite significant difference in the opposite direction. Using a broader definition of pain severity based on several questions nearly doubles the number of subjects in the severe pain group and shows even more significant results. The relationship of predominant bowel pattern to HRV is qualitatively different in the subgroup of patients with more severe pain than in the subgroup with less severe pain.     

Heart rate variability in the irritable bowel syndrome: a review of the literature

Background Patients with irritable bowel syndrome (IBS) often present with disturbances of bowel habits (diarrhea, constipation) and abdominal pain/discomfort that are modulated by the autonomic nerve system (ANS). In this narrative review, we analyzed studies that measured ANS functioning in IBS by means of heart rate variability (HRV). Methods The PUBMED was searched with the keywords ‘irritable bowel syndrome’ AND (‘heart rate variability’ OR ‘autonomic function’). We included only papers that used ‘traditional’ HRV indices and diagnosed IBS based on Manning or Rome criteria. Studies were sub‐grouped according to methodological features of HRV analysis (24‐h monitoring, short‐term laboratory records, records during sleep). Key Results Most studies reported no difference in HRV when the IBS population was compared to healthy controls. Dividing the IBS sample into subgroups – according to their predominant bowel symptoms, the severity of clinical course, the presence of depressive symptoms, or a history of abuse in the past – revealed changes in autonomic functioning. Conclusions & Inferences Patients with IBS appear to experience symptoms that may be the result of changes in ANS functioning. HRV measures in clinical routine may allow assessing these changes, but further studies performed in a standardized fashion should improve the validity of HRV measures for clinical research first.     

Subtle involvement of the parasympathetic nervous system in patients with irritable bowel syndrome

Abstract This study comprises assessment of autonomic function in irritable bowel syndrome (IBS) patients, focusing on meal-related changes. In 18 IBS patients (4 males, mean age 45±3.0 [SEM] years) and 19 healthy volunteers (6 males, mean age 41±3.5 years) blood pressure, heart rate, heart rate variability and muscle sympathetic nerve activity (MSNA) were assessed before, during and after consumption of a standardized meal. In pre- and postprandial phase Valsalva maneuver, cold pressor test (CPT) and deep breathing test were carried out and Visual Analog Scale (VAS) scores for nausea, bloating and pain were obtained. In the IBS group, the meal induced significantly higher VAS scores for pain (P=0.002) and bloating (P=0.02). During food intake, the increase in blood pressure, heart rate and MSNA was equal in patients and controls, but the increase of LF/HF ratio of heart rate variability was significantly higher in the IBS group (median [quartiles] 2.29 [1.14–3.00] versus 0.77 [0.25–1.81]; P=0.03). IBS patients scored lower on pre- and postprandial RRmax/RRmin ratio during deep breathing (DB ratio, P=0.03). The increase in MSNA (burst frequency) in response to CPT tended to be higher in the IBS patients (P=0.07). We conclude that reactivity to food intake, measured as muscle sympathetic nerve activity, is normal in IBS patients. The lower DB ratio and higher LF/HF ratio during food intake in IBS patients is an indication of a reduced parasympathetic reactivity. These results suggest that reduced baseline activity as well as responsiveness of the parasympathetic system could play a role in the pathogenesis of IBS.     

Heart rate variability in anorexia nervosa and the irritable bowel syndrome

Background Many studies have reported disturbances of heart rate variability (HRV) in patients with psychosomatic disorders such as anorexia nervosa (AN) and the irritable bowel syndrome (IBS). However, both have never been directly compared. Methods We compared HRV in AN (n = 21) and in IBS (n = 21) (all females) with 42 healthy female control subjects who were matched for age and in IBS to body mass index (BMI). Recovery periods between different cardiac load tests were compared with baseline recordings and tilt test to estimate time [mean successive difference (MSD)] and frequency domain (Goldberger dimension, frequency of HF peak location and HF power, log HF power) values and to assess general reactivity of the autonomic nervous system (ANS). Key Results Significantly longer inter‐beat intervals (IBIs) in AN patients and lower values of MSD in IBS patients were found in comparison with respective controls; both were independent from experimental conditions and are found in baseline recordings only. Both effects were independent of age and BMI. We also demonstrate a significant relationship between age, BMI and some HRV parameters. Conclusions & Inferences Opposite autonomic patterns were found in AN and IBS: stronger vagal withdrawal in IBS and weaker vagal inhibition in AN patients. Records made at rest and without any autonomic load may be representative for assessment of ANS function. Age and BMI should be taken into consideration during assessment of HRV data.     

The role of the endocannabinoid system in the pathophysiology and treatment of irritable bowel syndrome

Abstract  Irritable bowel syndrome (IBS) is a spectrum of disorders characterized by abdominal discomfort and pain, associated with altered bowel habits. Though gut motility, secretion and sensation may be altered in patients with IBS, the pathophysiology of this condition remains to be fully understood. The endocannabinoid system is involved in the regulation of numerous gastrointestinal functions including motility, sensation and secretion under both physiological and pathophysiological conditions. Activation of cannabinoid (CB)₁ and CB₂ receptors under various circumstances reduces motility, limits secretion and decreases hypersensitivity in the gut. Drugs that alter the levels of endocannabinoids in the gut also reduce motility and attenuate inflammation. In this review, we discuss the role of the endocannabinoid system in gastrointestinal physiology. We go on to consider the involvement of the endocannabinoid system in the context of symptoms associated with IBS and a possible role of this system in the pathophysiology and treatment of IBS.     

Ion channels,ion channel receptors,and visceral hypersensitivity in irritable bowel syndrome

Ion channels are expressed throughout the gastrointestinal system and regulate nearly every aspect of digestion, including fluid secretion and absorption, motility, and visceral sensitivity. It is therefore not surprising that in the setting of functional bowel disorders, such as irritable bowel syndrome (IBS), ion channels are often altered in terms of expression level and function and are a target of pharmacological intervention. This is particularly true of their role in driving abdominal pain through visceral hypersensitivity (VH), which is the main reason IBS patients seek medical care. In the study by Scanzi et al., in the current issue of this journal, they provide evidence that the T‐type voltage‐gated calcium channel (Ca_v) Ca_v3.2 is upregulated in human IBS patients, and is necessary for the induction of an IBS‐like disease state in mice. In this mini‐review, we will discuss the contribution of specific ion channels to VH in IBS, both in human patients and rodent models. We will also discuss how Ca_v3.2 may play a role as an integrator of multiple environmental stimuli contributing toward VH.