Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome

AIM： To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome （IBS）. Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function.
METHODS： Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities （visual analogue scale, VAS 0-100） during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously （heterotopic stimulation） were recorded in 40 female patients with IBS and 20 female healthy controls.
RESULTS： Rectal hypersensitivity （defined by 95% Cl of controls） was seen in 21 （53%）, somatic hypersensitivity in 22 （55%） and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 （-11 to -1） in controls, but increased rectal pain by 2 （-3 to ＋6） in all IBS patients （P 〈 0.05） and by 8 （-2 to ＋19） in IBS patients with somatic and visceral hypersensitivity （P 〈 0.02）.
CONCLUSION： A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.     

Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant irritable bowel syndrome (IBS): effect of a low-fat intraduodenal infusion

BACKGROUND: Visceral hypersensitivity is common in Irritable Bowel Syndrome (IBS) patients, and symptoms exacerbate postprandially. Yet the effects of nutrients on visceral sensitivity and symptoms in these patients have not been fully explored. AIMS: To evaluate the differences of visceral sensitivity and symptoms in healthy subjects and IBS patients during fasting and intraduodenal lipids infusion. METHODS: Graded rectal distensions at fixed tension levels were performed in 16 IBS patients (8 IBS-C and 8 IBS-D) and 6 healthy subjects before and during intraduodenal lipids infusion at 0.5 kcal/min. Tension levels were increased in 4 gr increments up to 64 gr or discomfort during both conditions. At each step, perception and symptoms were measured by means of a validated questionnaire. RESULTS: In basal conditions, perception thresholds in IBS patients and health were, respectively, 8 +/- 2 gr versus 32 +/- 9 gr (p < 0.001) with no changes during lipids. Intraduodenal lipids infusion significantly lowered threshold of discomfort in IBS patients in comparison to fasting (24 +/- 6 gr vs 34 +/- 4 gr; p < 0.05), while health tolerated all distension without discomfort. No differences of compliance, perception, or discomfort were observed between the two subgroups of patients at each tension step. The predominant symptom elicited in patients with IBS-C was abdominal pain (54%), while patients with IBS-D exhibited urgency (63%, p < 0.005); this pattern was maintained during lipids. CONCLUSIONS: Intraduodenal lipids increase visceral sensitivity in both IBS-C and IBS-D; symptoms specificity in response to rectal distension is maintained in the postprandial period. Lipids may be responsible for the postprandial symptoms exacerbation in IBS.     

Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity

OBJECTIVE: The aim was to determine whether lower visceral pain thresholds in irritable bowel syndrome (IBS) primarily reflect physiological or psychological factors. METHODS: Firstly, 121 IBS patients and 28 controls underwent balloon distensions in the descending colon using the ascending methods of limits (AML) to assess pain and urge thresholds. Secondly, sensory decision theory analysis was used to separate physiological from psychological components of perception: neurosensory sensitivity (p(A)) was measured by the ability to discriminate between 30 mm Hg vs 34 mm Hg distensions; psychological influences were measured by the report criterion-that is, the overall tendency to report pain, indexed by the median intensity rating for all distensions, independent of intensity. Psychological symptoms were assessed using the Brief Symptom Inventory (BSI). RESULTS: IBS patients had lower AML pain thresholds (median: 28 mm Hg vs 40 mm Hg; p<0.001), but similar neurosensory sensitivity (median p(A): 0.5 vs 0.5; p = 0.69; 42.6% vs 42.9% were able to discriminate between the stimuli better than chance) and a greater tendency to report pain (median report criterion: 4.0 ("mild" pain) vs 5.2 ("weak" pain); p = 0.003). AML pain thresholds were not correlated with neurosensory sensitivity (r = -0.13; p = 0.14), but were strongly correlated with report criterion (r = 0.67; p<0.0001). Report criterion was inversely correlated with BSI somatisation (r = -0.26; p = 0.001) and BSI global score (r = -0.18; p = 0.035). Similar results were seen for the non-painful sensation of urgency. CONCLUSION: Increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity.     

Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia

OBJECTIVE: Symptoms of irritable bowel syndrome (IBS) and fibromyalgia (FM) commonly coexist. We hypothesized that one of the mechanisms underlying this comorbidity is increased activation of brain regions concerned with the processing and modulation of visceral and somatic afferent information, in particular subregions of the anterior cingulate cortex (ACC). METHODS: Regional cerebral blood flow (rCBF) was assessed in age-matched female IBS (n = 10) and IBS + FM (n = 10) subjects using H(2)(15)O positron emission tomography during noxious visceral (rectal) and somatic pressure stimuli. RESULTS: GI symptom severity was significantly higher in the IBS patients compared with the IBS + FM patients (p < 0.05). In addition, IBS + FM patients rated somatic pain as more intense than their abdominal pain (p < 0.05). Whereas the somatic stimulus was less unpleasant than the visceral stimulus for IBS patients without FM, the somatic and visceral stimuli were equally unpleasant in the IBS + FM group. Group differences in regional brain activation were entirely within the middle subregion of the ACC. There was a greater rCBF increase in response to noxious visceral stimuli in IBS patients and to somatic stimuli in IBS + FM patients. CONCLUSION: Chronic stimulus-specific enhancement of ACC responses to sensory stimuli in both syndromes may be associated with cognitive enhancement of either visceral (IBS) or somatic (IBS + FM) sensory input and may play a key pathophysiologic role in these chronic pain syndromes.     

Visceral hypersensitivity following cold water intake in subjects with irritable bowel syndrome

Background Visceral hypersensitivity has been shown to be present in irritable bowel syndrome (IBS). This study sought to investigate rectal sensitivity and abdominal symptoms in IBS patients before and after 220 ml cold water intake. Methods A total of 60 IBS patients and 18 healthy controls participated in this study. Both the perception thresholds and defecation thresholds to rectal balloon distension were measured. Then, all subjects were asked to drink 220 ml 37°C warm water or 4°C cold water, and these steps were repeated 20 min later. Symptoms including abdominal pain/discomfort, bloating, and diarrhea were recorded during the study. Results Compared with the controls, the thresholds of initial sensation to rectal balloon distention in IBS patients were significantly lower while the defecation thresholds were higher in constipation-predominant IBS patients. After drinking cold water, the perception thresholds in IBS patients and the defecation thresholds in diarrhea-predominant IBS patients were further decreased. However, warm water intake did not change the perception thresholds significantly in either IBS patients or controls. A negative linear correlation was found between the symptoms and the visceral perception thresholds in diarrhea-predominant IBS patients who showed significant symptoms after cold water intake. Conclusion The results indicated that cold water intake leads to lowered visceral perception thresholds in IBS patients that were inversely relevant to the abdominal symptoms in symptomatic diarrhea-predominant IBS patients. The alteration of rectal sensitivity and abdominal symptoms following cold water stimulation provided further objective evidence for visceral hypersensitivity in IBS patients.     

Perceptual responses in patients with inflammatory and functional bowel disease

BACKGROUND AND AIMS: Enhanced visceral sensitivity following a transient inflammatory process in the gut has been postulated as an aetiological mechanism of irritable bowel syndrome (IBS). In this study we compared perceptual responses to rectosigmoid distension in patients with mild chronic inflammation of the rectum (ulcerative colitis (UC)) and patients without mucosal inflammation (IBS) to determine if chronic low grade mucosal inflammation may be a plausible explanation for rectosigmoid hypersensitivity reported in both IBS and UC patients. METHODS: UC disease activity was quantified using activity index scores. Perception thresholds for discomfort during rectosigmoid distension were compared between 11 UC patients with quiescent or mild disease activity, 18 IBS patients, and 13 healthy controls. RESULTS: Although UC activity index scores negatively correlated with perceptual thresholds for discomfort (r=-0.76, p=0.016), UC patients had higher discomfort thresholds compared with IBS patients and controls before (p=0.02) and after (p<0.001) a noxious sigmoid conditioning stimulus. CONCLUSIONS: Rectal perception was attenuated in UC but enhanced in IBS. In chronic mild inflammation, activation of antinociceptive mechanisms may prevent the development of visceral hyperalgesia. Low grade mucosal inflammation alone is unlikely to be responsible for symptoms in functional gastrointestinal disorders.     

腹部冷刺激对肠易激综合征患者内脏感觉阈值的影响

目的 探讨腹部冷刺激对肠易激综合征（IBS）患者内脏褡珠影响。方法 通过脐部放置冰袋加直肠球囊内充气（时相性）和直肠球囊内注入冰水，观察46例IBS患者症状变化及直肠初始感觉阈值和排便阈值，并与13例健康人对照。结果 （1）脐部放置冰袋加直肠球囊内充气可诱发部分患者症状的产生，如腹痛、腹部不适等，但对初始感觉阈值和排便阈值无明显影响。（2）直肠球囊内注入冰水后，除便秘型IBS的排便阈值稍有所增加但差异不显著外，其余患者初始感觉阈值及排便阈值均明显低于对照组，以腹泻型变化最明显。结论 腹部冷刺激对IBS患者内脏感觉阈值无明显影响，而直肠内冷刺激可明显降低初始感觉阈值，说明IBS患者感觉过敏并非整体痛阈降低所致，而仅指内脏感觉过敏。     

Repetitive rectal painful distention induces rectal hypersensitivity in patients with irritable bowel syndrome

Background A reduced rectal perceptual threshold has been reported in patients with irritable bowel syndrome (IBS), but this phenomenon may be induced by a comorbid psychological state. We evaluated the rectal pain threshold at baseline and after conditioning (repetitive rectal painful distention: RRD) in patients with IBS or functional abdominal pain syndrome (FAPS), which is an abdominal pain disorder, and in healthy controls, and determined whether rectal hypersensitivity is a reliable marker for IBS. Methods The rectal sensory threshold was assessed by a barostat. First, a ramp distention of 40 ml/min was induced, and the threshold of pain and the maximum tolerable pressure (mmHg) were measured. Next, RRD (phasic distentions of 60-s duration separated by 30-s intervals) was given with a tracking method until the subjects had complained of pain six times. Finally, ramp distention was induced again, and the same parameters were measured. The normal value was defined by calculating the 95% confidence intervals of controls. Results Five or six of the seven IBS patients showed a reduced rectal pain threshold or maximum tolerable pressure, respectively, at baseline. In all patients with IBS, both thresholds were reduced after RRD load, but they were reduced in none of the patients with FAPS. RRD significantly reduced both thresholds in the IBS group (P < 0.05), but it had no effect in the control or FAPS groups. Conclusions Rectal hypersensitivity induced by RRD may be a reliable marker for IBS. Conditioning-induced visceral hypersensitivity may play a pathophysiologic role in IBS.     

Evaluation of colonic sensory thresholds in IBS patients using a barostat

To study the role of abnormal visceral perception in the pathophysiology of the irritable bowel syndrome (IBS), we evaluated colonic tone and visceral perception during intracolonic distension using a flaccid balloon connected to a computerized barostat and placed in the descending colon of IBS patients and healthy controls. In the first part of the study, basal colonic tone and response to pharmacological (neostigmine and glucagon) and physiological (1000-kcal meal) stimuli were recorded in nine IBS patients. Colonic tone increased by 72±27% after injection of neostigmine and decreased by 88±62% after glucagon. After the meal, the maximal increase in colonic tone was 76±31% with the total response to the meal lasting 109.7±32.0 min. In the second part of the study, symptomatic responses (discomfort and pain thresholds) and pressure variations were evaluated during two different methods of distension (stepwise and intermittent) in a randomized order in the nine IBS patients and six healthy controls. Each distension method was repeated twice in IBS patients to study reproducibility. In IBS patients, the mean discomfort threshold volume was 172±76 ml when using stepwise and 167±43 ml when using intermittent distension. The mean pain threshold volume was 250±25 ml when using stepwise and 211±22 ml when using intermittent distension, this difference being statistically significant (P<0.02). Discomfort and pain threshold volumes recorded during the first session of the same distension method were not different from those recorded during the second one. When comparing IBS patients to controls, the pain threshold was reached at a volume 300 ml in all IBS patients versus only one control when using stepwise distensions (P<0.001) and in all IBS patients versus no control when using intermittent distensions (P<0.001). Intracolonic pressure-volume curves were similar in patients and controls. In conclusion, isovolumic distension of the colon is a reproducible method of evaluating viscerosensitivity, which is significantly increased in IBS patients. This increased viscerosensitivity is not related to abnormal colonic compliance and may, alone or in combination with other colonic abnormalities, explain the symptoms of irritable bowel syndrome.     

Intrarectal injection of glycerol induces hypersensitivity to rectal distension in healthy subjects without modifying rectal compliance

BACKGROUND: Rectal sensory thresholds are lowered in patients with irritable bowel syndrome (IBS), reflecting visceral hyperlagesia, which might be related to subclinical inflammation. AIM: To evaluate the effects of an intraluminal injection of glycerol, a mucosal irritant, on rectal tone and perception of distension in 12 healthy subjects. METHODS: Rectal tone was evaluated with a barostat. First sensation, need to defecate and pain thresholds were evaluated during isobaric phasic distensions, before and 20 and 120 min after injection of 10 ml glycerol in the rectum. RESULTS: Baseline bag volume (97.9 +/- 56.2 ml) significantly decreased 20 min (49.7 +/- 42.2 ml; P= 0.026) and 120 min (66.5 +/- 38.3 ml; P= 0.050) after injection of glycerol, indicating its hypertonic effect. The pressure defining sensory thresholds was decreased significantly 20 min after glycerol injection: first sensation, 14.6 +/- 2.9 versus 18.3 +/- 7.2 mm Hg (P = 0.01); need to defecate, 19.6 +/- 3.7 versus 26.0 +/- 6.9 mm Hg; pain, 23.8 +/- 4.5 versus 35.6 +/- 9.5 mm Hg (P = 0.001). This effect was maintained for 120 min after injection of glycerol. Slopes of the compliance curves did not differ before and after injection of glycerol. CONCLUSIONS: Intraluminal injection of glycerol significantly increases rectal tone and sensitizes healthy volunteers to rectal distension, since they show significantly lower thresholds after glycerol. This could constitute a model of visceral hypersensitivity in healthy volunteers.     

Octreotide increases thresholds of colonic visceral perception in IBS patients without modifying muscle tone

Effects of octreotide (1.25 µg/kg subcutaneously) on colonic tone and visceral perception were evaluated in 10 IBS patients, using a barostat and compared to placebo in a double-blind crossover study. Colonic sensory thresholds were also studied in healthy controls for comparison with IBS patients. Colonic tone was reflected by variations in volume of the barostat balloon. Baseline volume was 117±38 ml and was not modified by placebo (122±40 ml) or octreotide (106±42 ml). After the meal, maximal decrease in balloon volume was 75±4% following placebo (P<0.001) beginning after 9±3 min and lasting 136±17 min. Following octreotide, the maximal decrease was 69±16% (NS vs placebo), after 10±3 min and lasting 140±22 min. In the second part, discomfort and pain thresholds were evaluated during isobaric distensions (4 mm Hg increments, 5-min duration, 5-min interval with return to pressure 0 between each). The pressure inducing discomfort was 21.2±5.9 mm Hg following placebo vs 29.6±6.6 mm Hg following octreotide (P<0.01). The pressure inducing pain was 24.8±7.3 mm Hg following placebo vs 33.2±7.3 mm Hg following octreotide (P<0.01). In healthy subjects, discomfort and pain were induced by colonic distensions at a mean intraballoon pressure of 32.7±5.8 mm Hg and 36.7±3.9 mm Hg, respectively. Compliance curves were not different following placebo and octreotide. Octreotide significantly increases thresholds for visceral perception in IBS patients without modifying compliance during distension nor colonic tone.     

Differences in gastric mechanosensory function after repeated ramp distensions in non-consulters with dyspepsia and healthy controls

BACKGROUND: Abnormal visceral mechano-sensory function has been reported in 50% of non-ulcer (functional) dyspepsia patients. However, only a minority of subjects with functional dyspepsia ever seek medical attention. Whether factors promoting health care seeking behaviour explain visceral hypersensitivity is unknown. Decreased rectal thresholds following sigmoid mechanical stimulation have been observed in irritable bowel but this mechanism has not been evaluated in functional dyspepsia. AIMS: To compare visceral mechanosensory function in healthy asymptomatic subjects and non-consulters with chronic unexplained dyspepsia. METHODS: Forty two volunteers were recruited: 10 had a history of chronic or recurrent upper abdominal pain or discomfort as assessed by a standardised questionnaire, and Helicobacter pylori status was determined (ELISA and (13)C urea breath test). Eight H pylori negative, currently asymptomatic dyspeptic subjects who were non-consulters and eight asymptomatic age and sex matched H pylori negative controls were enrolled. With a barostat bag in the proximal part of the stomach, visceral perception thresholds were determined by random tracking. Thereafter, standardised ramp distensions were performed (2 mm Hg increments, duration of each pressure step 30 seconds, maximum pressure 35 mm Hg (or occurrence of pain)) and tracking of sensory thresholds and ramp distension repeated every 30 minutes for a total of two hours. RESULTS: Overall, thresholds for first perception were significantly lower in dyspeptic subjects compared with asymptomatic controls (12.5 (0.6) mm Hg v 17.5 (1.0) mm Hg; p<0.02). After repeated ramp distensions, thresholds for first perception significantly increased by 3.6 (0.7) mm Hg in healthy subjects compared with 0.1 (1.4) mm Hg in subjects with dyspepsia (p<0.05 dyspeptics v controls). CONCLUSIONS: (1) Repeated mechanical stimulation increases visceral sensory thresholds in asymptomatic subjects while thresholds remain unchanged in dyspeptics. (2) Visceral hyperalgesia occurs in dyspeptic subjects who are not health care seekers.     

Alterations in cerebral potentials evoked by rectal distention and drinking ice water in patients with irritable bowel syndrome

AIM: Visceral hypersensitivity has been found to be present in irritable bowel syndrome (IBS). The current study sought to study visceral afferent hypersensitivity in IBS patients and obtain further objective evidence of alterations in intestinal afferent pathways in IBS patients by cerebral evoked potentials (CEP). METHOD: We studied 30 female IBS patients and 12 female healthy subjects. Rectal perception thresholds to balloon distention were measured and CEP was recorded in response to rhythmic rectal distention (two distention series, each of 100 repetitions at a frequency of 1 Hz) at the volume of perception thresholds. All subjects were then asked to drink 220 mL 4 degrees C ice water and the above steps were repeated 20 min later. RESULTS: Rectal distention led to recognizable and reproducible CEP. Compared to healthy subjects, IBS patients demonstrated significantly shorter N1, P1 and N2 latencies (P < 0.05). After drinking ice water, IBS patients exhibited further shortened N1, P1 and N2 latencies (P < 0.05), but drinking did not alter the latencies of healthy controls and the amplitudes of both IBS patients and healthy controls. CONCLUSION: The shorter latency of cerebral potentials evoked by rectal distention and ice water stimulation in IBS patients provided further objective evidence for defective visceral afferent transmission in IBS patients.     

An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome

BACKGROUND/AIMS: Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood. SUBJECTS: We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS. METHODS: Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined. RESULTS: Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group. CONCLUSIONS: Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.     

Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress

BACKGROUND AND AIMS: Stress often worsens the symptoms of irritable bowel syndrome (IBS). We hypothesised that this might be explained by altered neuroendocrine and visceral sensory responses to stress in IBS patients.Subjects and METHODS: Eighteen IBS patients and 22 control subjects were assessed using rectal balloon distensions before, during, and after mental stress. Ten controls and nine patients were studied in supplementary sessions. Rectal sensitivity (thresholds and intensity-visual analogue scale (VAS)) and perceived stress and arousal (VAS) were determined. Plasma levels of corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), cortisol, noradrenaline, and adrenaline were analysed at baseline, immediately after stress, and after the last distension. Heart rate was recorded continuously. RESULTS: Thresholds were increased during stress in control subjects (p<0.01) but not in IBS patients. Both groups showed lower thresholds after stress (p<0.05). Repeated distensions without stress did not affect thresholds. Both groups showed increased heart rate (p<0.001) and VAS ratings for stress and arousal (p<0.05) during stress. Patients demonstrated higher ratings for stress but lower for arousal than controls. Basal CRF levels were lower in patients (p<0.05) and increased significantly during stress in patients (p<0.01) but not in controls. Patients also responded with higher levels of ACTH during stress (p<0.05) and had higher basal levels of noradrenaline than controls (p<0.01). Controls, but not patients, showed increased levels of adrenaline and noradrenaline in response to stress (p<0.05). CONCLUSIONS: Stress induced exaggeration of the neuroendocrine response and visceral perceptual alterations during and after stress may explain some of the stress related gastrointestinal symptoms in IBS.     

Perception of electrocutaneous stimuli in irritable bowel syndrome

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are common conditions with some similarities, but different perceptual responses to somatic and visceral stimuli. The purpose of this study was to assess in a large group of IBS patients the somatic perception by transcutaneous electrical nerve stimulation (TENS) and its relation to the level of severity and presence of FMS. METHODS: In 99 patients grouped by the validated functional bowel disorder severity index (FBDSI) in mild, moderate, and severe IBS and in 33 healthy controls (HC), we studied discomfort thresholds and perception of somatic stimuli at control (hands and elbows) and active (trapezius) sites by TENS and by using a specific questionnaire. RESULTS: The use of TENS showed that IBS showed significant higher thresholds and lower perception cumulative score compared to HC. The severity of IBS is significantly associated with age and mean control site values for discomfort and borderline associated with gender in the ordinal model constructed for the ascending series protocol. The severity of IBS is also significantly associated with the active cumulative perception score in the long stimulus protocol. Due to limited sample size of IBS men with FMS, analyses of discomfort thresholds and cumulative perception score by FMS were done only for women. IBS women without FMS had significantly higher mean control site values for discomfort and significantly lower active cumulative perception score than HC. IBS women with FMS had significantly lower mean active site values for discomfort thresholds than IBS women without FMS (Dunn's test p < 0.05). CONCLUSIONS: IBS patients showed somatic hypoalgesia to electrical stimuli. The severity of IBS and the presence of FMS influence the perception of somatic stimuli induced by TENS.     

Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls

BACKGROUND AND AIMS: Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI). PATIENTS AND METHODS: fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0 = none, 10 = maximal). RESULTS: Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (-1.5 (interquartile range -2 to -1); p = 0.001) but not in IBS-C (-0.7 (-1 to 0.5)), IBS-D (-0.5 (-1.5 to 0.5)), or in all IBS patients (0 (-1.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain. CONCLUSIONS: IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.     

Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, possibly related to abnormal brain-gut communication. Positron emission tomography imaging has suggested specific central nervous system (CNS) abnormalities in visceral pain processing in IBS. This study aimed to determine (1) if functional magnetic resonance imaging (fMRI) detects CNS activity during painful and nonpainful visceral stimulation; and (2) if CNS pain centers in IBS respond abnormally. METHODS: fMRI was performed during nonpainful and painful rectal distention in 18 patients with IBS and 16 controls. RESULTS: Rectal stimulation increased the activity of anterior cingulate (33/34), prefrontal (32/34), insular cortices (33/34), and thalamus (32/34) in most subjects. In IBS subjects, but not controls, pain led to greater activation of the anterior cingulate cortex (ACC) than did nonpainful stimuli. IBS patients had a greater number of pixels activated in the ACC and reported greater intensity of pain at 55-mm Hg distention than controls. CONCLUSIONS: IBS patients activate the ACC, a critical CNS pain center, to a greater extent than controls in response to a painful rectal stimulus. Contrary to previous reports, these data suggest heightened pain sensitivity of the brain-gut axis in IBS, with a normal pattern of activation.     

Functional brain imaging in irritable bowel syndrome with rectal balloon－distention by using fMRI

AIM: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls. METHODS: Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects. RESULTS: Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls. CONCLUSION: Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.     

Heightened visceral sensation in functional gastrointestinal disease is not site-specific

Alteration in visceral sensation locally at the site of presumed symptom origin in the gastrointestinal tract has been proposed as an important etiopathological mechanism in the so-called functional bowel disorders. Patients presenting with one functional gastrointestinal syndrome, however, frequently have additional symptoms referable to other parts of the gut, suggesting that enhanced visceral nociception may be a panintestinal phenomenon. We measured the sensory thresholds for initial perception (IP), desire to defecate (DD), and urgency (U) in response to rectal balloon distension, and the thresholds for initial perception and for discomfort in response to esophageal balloon distension in 12 patients with irritable bowel syndrome (IBS) and 10 patients with functional dyspepsia (FD), in comparison with healthy controls. As expected, IBS patients exhibited lower rectal sensory thresholds than controls (P<0.0001), but in addition had significantly lower sensory thresholds for both perception and discomfort evoked by balloon distension of the esophagus (mean ±SEM: 8.8±1.3 ml vs 12.1±1.5 ml (P<0.05) and 12.2±1.4 ml vs 16.4±1.4 ml (P<0.02) respectively. Patients with FD showed similarily enhanced esophageal sensitivity, with thresholds for perception and discomfort of 8.1±0.9 ml (P<0.02), and 10.1±1.0 ml (P<0.001), respectively, but were also found to have sensory thresholds for rectal distension similar to those observed in the IBS group, significantly lower than in controls: IP 45.0±17.6 vs 59.3±1.5 ml (P<0.001), DD 98.0±17.9 vs 298.7±9.0 ml (P<0.0001), U 177.2±25.4 vs 415.1 ±12.6 ml (P<0.0001). Somatic nerve sensory thresholds showed no significant differences between the patient and control groups. Our findings indicate that alterations in visceral sensitivity in functional gastrointestinal disease affect sites in the gut other than the putative organ of symptom origin, supporting the concept of generally enhanced visceral awareness in patients with functional bowel disorders.