Cholecystokinin octapeptide increases rectal sensitivity to pain in healthy subjects

Hypersensitivity during rectal distension has been demonstrated in irritable bowel syndrome (IBS). Studies performed in animals and indirect data in humans suggest that cholecystokinin (CCK) could modulate visceral sensations. The aim of this study was to assess the effects of i.v. infused sulphated cholecystokinin octapeptide (CCK-OP) on rectal sensitivity in response to distension. In eight healthy subjects, rectal sensitivity and compliance were determined during a randomized double-blind study, with four sessions each separated by 7 days. Sensory thresholds and rectal compliance were assessed during slow-ramp (40 mL min-1) and rapid-phasic distensions (40 mL s-1, 5 mmHg stepwise, 1-min duration), and were compared before and during continuous infusion of either saline or CCK-OP at 5, or 20 or 40 ng kg-1 h-1. During rapid phasic distension but not during slow ramp distension, CCK-OP at 40 ng kg-1 h-1 produced a significant decrease in sensory thresholds compared with the basal period. Rectal compliance was not modified by any infusion. At pharmacological doses, CCK-OP decreases sensory thresholds during rapid phasic distension that may preferentially stimulate serosal mechanoreceptors, but has no effect on mucosal mechanoreceptors stimulated during slow ramp distensions. Modulation of rectal sensitivity by CCK could be implicated in the pathogenesis of the rectal hypersensitivity observed in IBS.     

Assessment of rectal afferent neuronal function and brain activity in patients with constipation and rectal hyposensitivity

Background Blunted rectal sensation (rectal hyposensitivity: RH) is present in almost one‐quarter of patients with chronic constipation. The mechanisms of its development are not fully understood, but in a proportion, afferent dysfunction is likely. To determine if, in patients with RH, alteration of rectal sensory pathways exists, rectal evoked potentials (EPs) and inverse modeling of cortical dipoles were examined. Methods Rectal EPs (64 channels) were recorded in 13 patients with constipation and RH (elevated thresholds to balloon distension) and 11 healthy controls, in response to electrical stimulation of the rectum at 10 cm from the anal verge using a bipolar stimulating electrode. Stimuli were delivered at pain threshold. Evoked potential peak latencies and amplitudes were analyzed, and inverse modeling was performed on traces obtained to determine the location of cortical generators. Key Results Pain threshold was higher in patients than controls [median 59 (range 23–80) mA vs 24 (10–55) mA; P = 0.007]. Median latency to the first negative peak was 142 (±24) ms in subjects compared with 116 (±15) ms in controls (P = 0.004). There was no difference in topographic analysis of EPs or location of cortical activity demonstrated by inverse modeling between groups. Conclusions & Inferences This study is the first showing objective evidence of alteration in the rectal afferent pathway of individuals with RH and constipation. Prolonged latencies suggest a primary defect in sensory neuronal function, while cerebral processing of visceral sensory information appears normal.     

Influence of age on rectal tone and sensitivity to distension in healthy subjects

Hypersensitivity to rectal distension is frequently observed in patients with irritable bowel syndrome (IBS). However, few data are available about the influence of age on rectal sensory thresholds and tone. The aim of this study was to measure rectal sensory thresholds and tone with a barostat in 12 healthy subjects (aged 86 +/- 4 years, eight females, four males) as compared with 12 young healthy male controls (26 +/- 1 years). Isobaric phasic distensions were performed in the fasted state (increment of 4 mmHg, steps of 5 min, interval of 5 min). Rectal tone changes were then measured as changes in volume of the barostat bag, the pressure being kept constant. After a baseline recording of 1 h, a 1000-kcal meal was served and the tone recorded until return to baseline. Rectal sensory thresholds were significantly higher in aged subjects. First sensation, sensation of urge to defaecate and sensation of pain were triggered at 21.1 +/- 3.2 mmHg, 30.4 +/- 5.4 mmHg and 40.5 +/- 5.0 mmHg, respectively, in aged subjects, vs 13.3 +/- 4.6 mmHg (P < 0.05), 20.7 +/- 1.0 mmHg (P < 0.001) 31.3 +/- 1.7 mmHg (P < 0.001) in controls. Rectal compliance was not significantly different between the two groups. Mean barostat bag volume was 104 +/- 13 mL in fasting aged subjects and 125 +/- 23 mL in controls (NS). After the meal, the barostat bag volume decreased by 69 +/- 11% during 85 +/- 17 min in aged subjects and 75 +/- 14% during 89 +/- 15 min in young controls (NS). Rectal sensory thresholds triggered by distension are increased in aged healthy subjects while compliance and tone are not different. Age should be considered as a confounding factor when studying rectal sensitivity and further studies in aged patients with IBS should include a group of control subjects within the same range of age as studied patients.     

Circadian variation of rectal sensitivity and gastrointestinal peptides in healthy volunteers

Abstract  The aim of our study was to identify diurnal variation of perception of rectal distension and the release of gastroenteropancreatic hormones. In 12 healthy male volunteers (25 years, range 22–32), a rectal balloon distension was performed. Rectal perception thresholds (minimal, urge and pain) and rectal compliance were double-measured with a computer-controlled barostat at seven standardized time points during the day (from 16.00 to 14.00 hours the following day). Blood samples were taken 30 min before and after each rectal distension procedure to determine plasma levels of cholecystokinin (CCK), pancreatic polypeptide (PP) and motilin. Sensory thresholds for urge and pain varied significantly with the time of day, with higher threshold levels in the evening than in the morning hours. Bowel wall compliance showed as well-significant variance at pain threshold and was higher during daytime than in the evening or at night. In contrast to motilin, release of CCK and PP also showed a significant variation depending on daytime. Perception of rectal distension stimuli as well as compliance was independent of intake of food and peptide hormone levels, but CCK and PP levels increased with food, and PP levels decreased with rectal distension. Significant differences in the perception of rectal distension stimuli for urge and pain depending on daytime were found, but the release of gastrointestinal peptides seemed not to be involved. This circadian variation needs to be taken into account in patients and volunteer studies.     

Possible role of nitric oxide in visceral hypersensitivity in patients with irritable bowel syndrome

BACKGROUND: Visceral hypersensitivity is a consistent finding in a considerable proportion of patients with irritable bowel syndrome (IBS), and may provide a physiological basis for the development of IBS symptoms. In this study, we aimed to confirm the hypothesis that nitric oxide (NO) is involved in maintaining visceral hypersensitivity in IBS. Ten healthy volunteers (HV) and 12 IBS patients with documented hypersensitivity to rectal distension underwent a rectal barostat study. The effect of placebo and the specific NO synthase inhibitor NG -monomethyl-L-arginine (L-NMMA) on resting volume, rectal sensitivity to distension and rectal compliance was evaluated in a double-blind, randomized, cross-over fashion. NG -monomethyl-L-arginine did not alter resting volumes in HV or IBS patients. In HV, l-NMMA did not alter rectal sensory thresholds compared to placebo (45 +/- 3 and 46 +/- 3 mmHg, respectively). In contrast, L-NMMA significantly increased the threshold for discomfort/pain in IBS patients (placebo: 18 +/- 2, l-NMMA: 21 +/- 3 mmHg, P < 0.05). Rectal compliance was not affected by L-NMMA. Although NO does not seem to play a major role in normal rectal sensation or tone, we provide evidence that NO may be involved in the pathophysiology of visceral hypersensitivity in IBS.     

Sacral nerve stimulation and rectal function: results of a prospective study in faecal incontinence

Abstract The mechanisms of action of sacral nerve stimulation (SNS) to treat faecal incontinence remain poorly understood. The aims of our study were: (i) to measure the effect of SNS on rectal function and (ii) to evaluate rectal function as a predictive factor of clinical response to SNS. Rectal function was studied before and 3 months after permanent SNS in 18 patients (17 women, mean age 58.5 years) with faecal incontinence, using an electronic barostat. Rectal sensitivity and volume variations were recorded during isobaric distensions. Three months after SNS, 14 patients had a significant improvement of faecal incontience symptoms and four had not. Baseline ‘maximal tolerated volume’ was significantly lower in the positive response group (210 ± 56 vs 286 ± 30 mL, P = 0.02). Baseline rectal compliance was lower in patients with a positive response than those without, although this difference did not reach significance (6.2 ± 3.2 vs 9.2 ± 2.9 mL mmHg^?1,P = 0.10). Rectal compliance was not significantly modified by SNS. Our results suggest that an increased rectal capacity as measured by the maximal tolerated volume may be a predictive factor of poor response to SNS in faecal incontinence. SNS does not significantly modify rectal function.     

Rectal hyposensitivity: evaluation of anal sensation in female patients with refractory constipation with and without faecal incontinence.

Rectal hyposensitivity (RH) is commonly found in patients with intractable constipation, faecal incontinence or both. Anal sensation may also be blunted in these conditions. We aimed to determine whether RH is associated with anal hyposensitivity, which may reflect a combined viscero-somatic neuropathy. One hundred and fifty-eight female patients with chronic constipation underwent physiological investigation including rectal sensation to volumetric balloon distension, and distal anal mucosal sensation to electrostimulation. Data were also obtained from 32 healthy female volunteers. Anal mucosal electrosensory thresholds were significantly higher in patients compared with volunteers (median: 2.4 mA, range: 0.4-19.6 vs 1.1 mA, range: 0.1-4.2, respectively), although the patient group was older (P < 0.0001), but there was no difference (P = 0.572) in the incidence of blunted anal sensation between those with normal rectal sensation (n = 113, 20% abnormal) and RH (n = 45, 24% abnormal). Irrespective of rectal sensory function, there was a strong association between symptom duration (P = 0.012) and anal hyposensitivity. One-fifth of constipated female patients had evidence of diminished anal sensation. However, the presence of RH was not associated with an increased frequency of anal hyposensitivity, thereby suggesting that different aetiopathogenic mechanisms underlie the development of anal and rectal hyposensitivity. Further studies in carefully selected, homogenous patient populations are necessary to elucidate these mechanisms.     

Pre-experimental stress in patients with irritable bowel syndrome: high cortisol values already before symptom provocation with rectal distensions

Abstract  Stress is known to affect symptoms of irritable bowel syndrome (IBS) probably by an alteration of visceral sensitivity. We studied the impact of maximal tolerable rectal distensions on cortisol levels in patients with IBS, chronic constipation and controls, and evaluated the effect of the experimental situation per se . In twenty-four IBS patients, eight patients with chronic constipation and 15 controls salivary cortisol was measured before and after repetitive maximal tolerable rectal balloon distensions and at similar times in their usual environment. Rectal sensitivity thresholds were determined. IBS patients but not controls and constipation patients had higher cortisol levels both before and after the experiment compared with similar times on an ordinary day in their usual environment ( P  = 0.0034 and 0.0002). There was no difference in salivary cortisol level before compared with after rectal distensions. The IBS patients had significantly lower thresholds for first sensation, urge and maximal tolerable distension than controls ( P  = 0.0247, 0.0001 and <0.0001) and for urge and maximal tolerable distension than patients with constipation ( P  = 0.006 and 0.013). IBS patients may be more sensitive to expectancy stress than controls and patients with constipation according to salivary cortisol. Rectal distensions were not associated with a further significant increase in cortisol levels.     

Abnormal rectal motor physiology in patients with irritable bowel syndrome

A contentious issue is whether irritable bowel syndrome (IBS) patients have abnormal rectal motor physiology. Our aim was to determine whether IBS patients have abnormal rectal responses to low (urge producing) or high (pain producing) distension pressures. The IBS patients and healthy controls underwent five series of isobaric rectal distensions to examine volume-pressure relationships and rectal accommodation: (i) ascending stepwise distensions terminating upon report of moderate pain, (ii) phasic and (iii) tonic distensions at a single low pressure producing a moderate sensation of urge to defecate (iv) phasic and (v) tonic distensions at a single high pressure producing a moderate pain sensation. The IBS patients demonstrated a lower rectal volume-pressure ratio during repetitive single-pressure phasic distensions, and a slower rate of rectal accommodation during low (but not high) pressure tonic distensions. However, dynamic compliance during ascending stepwise distensions and the change in rectal volume during tonic distension were not significantly different from controls. Rectal abnormality was readily demonstrated by determining the volume-pressure ratio using a small number of repetitive single-pressure distensions, supporting the hypothesis that IBS patients have abnormal rectal motor physiology. We propose that a peripheral neuromuscular substrate may contribute to the pathogenesis of IBS.     

Influence of experimentally induced anxiety on rectal sensorimotor function in healthy humans

Abstract Psychological processes, especially anxiety, may have an influence on visceral perception and gastrointestinal (GI) motor function, thereby eliciting or aggravating GI symptoms. Anxiety has been shown to affect gastric sensorimotor function but it is conceivable that anxiety affects not only the stomach but also other parts of the GI tract, such as the rectum. The aim of this study was to investigate whether experimentally induced anxiety would alter rectal sensorimotor function in health. Eighteen healthy subjects (mean age 26.97 ± 1.75 years) underwent a rectal barostat study. To assess sensitivity to rectal distension and rectal compliance, stepwise isobaric distension was performed during anxious and neutral emotional state. Two methods of emotion induction were used simultaneously: audiotape assisted recall of a neutral or anxious autobiographical experience and viewing of a set of validated neutral or fearful facial expressions. Anxiety levels were assessed by means of the Spielberger State‐Trait Anxiety Inventory (STAI) and anxiety scores on a Likert scale. Anxiety scores (AUC: 2.11 ± 1.45 vs 42.78 ± 6.17 mm mmHg, P < 0.0001) and STAI scores (36.06 ± 2.09 vs 45.56 ± 2.52, P = 0.005) confirmed the efficacy of anxiety induction. Rectal compliance was not different during anxious compared with neutral emotional state (11.62 ± 0.93 vs 10.61 ± 0.96 mL mmHg^?1, P = NS). Pressure and volume thresholds inducing discomfort during rectal distension were not significantly different during anxious and neutral emotional state (29.33 ± 1.41 vs 29.78 ± 1.49 mmHg, P = NS and 249.26 ± 16.22 vs 231.38 ± 21.19 mL, P = NS respectively). Contrary to its influence on gastric sensorimotor function, experimentally induced anxiety does not affect rectal sensitivity or rectal compliance in healthy subjects.     

Distension technique influences the relationship between colonic and rectal hypersensitivity in irritable bowel syndrome

In irritable bowel syndrome (IBS), it remains unclear whether rectal hypersensitivity is a 'marker' of colonic hypersensitivity. Our aim was to examine the relation between colonic and rectal sensitivity in IBS patients, comprising phasic and ramp distension techniques. Twenty IBS patients and 12 healthy subjects (N) underwent stepwise ramp and random phasic barostat distensions in the colon and rectum in random order. The sensory threshold pressure (ramp distension) and the visual analogue scale score (VAS, phasic distension), for pain and non-pain, were recorded. Colonic thresholds were lower, and VAS scores were generally higher, for pain and non-pain sensitivities in IBS compared to N. Rectal thresholds were lower, and VAS scores were higher, for pain but not for non-pain, in IBS compared to N. In IBS, for phasic distension, there was good correlation between the colon and rectum for non-pain (e.g. at 16 mmHg, r=0.59, P=0.006) and pain (r=0.60, P=0.006) sensitivities. In contrast, there was no significant correlation between the colon and rectum for ramp distension. In conclusion, colonic and rectal sensitivity in IBS are correlated in response to phasic but not ramp barostat distensions. The rectum serves as a legitimate 'window' for evaluating colonic hypersensitivity in IBS, provided that phasic distensions are employed.     

Effects of the corticotropin-releasing factor (CRF) on rectal afferent nerves in humans

Abstract Corticotropin-releasing factor (CRF) released in the gastrointestinal mucosa from immune cells or enterochromaffin cells may play a role in the modulation of rectal afferent function. In the current study we evaluated the effects of peripherally administered CRF on afferent mechanisms in the human rectum. We used rectal balloon distention in seven healthy volunteers to evaluate the effect of CRF (1 μ/kg) on visceral afferents originating in the rectum which are involved in the following functions: thresholds and intensity of conscious perception, receptive relaxation, reflex inhibition of internal anal sphincter and a viscerosomatic reflex. Rectal mechanoreceptors were stimulated either by distending the rectum using a volume ramp (40 and 400 mL/min), or by intermittent phasic distention. CRF decreased the thresholds and increased the intensity for the sensation of discomfort in response to both ramp and phasic distention. During slow ramp distention, CRF also lowered the stool threshold. CRF increased rectal compliance during slow ramp distention without affecting the rate of receptive relaxation or the inflection point of the compliance curve. CRF had no effect on viscerosomatic referral patterns, or on the rectoanal inhibitory reflex. These findings are consistent with a dual effect of CRF on afferent pathways mediating perception of aversive rectal sensations, and on rectal smooth muscle.     

Function and morphology correlates of rectal nerve mechanoreceptors innervating the guinea pig internal anal sphincter

Background Mechanoreceptors to the internal anal sphincter (IAS) contribute to continence and normal defecation, yet relatively little is known about their function or morphology. We investigated the function and structure of mechanoreceptors to the guinea pig IAS. Methods Extracellular recordings from rectal nerve branches to the IAS in vitro, combined with anterograde labeling of recorded nerve trunks, were used to characterize extrinsic afferent nerve endings activated by circumferential distension. Key Results Slowly adapting, stretch‐sensitive afferents were recorded in rectal nerves to the IAS. Ten of 11 were silent under basal conditions and responded to circumferential stretch in a saturating linear manner. Rectal nerve afferents responded to compression with von Frey hairs with low thresholds (0.3–0.5 mN) and 3.4 ± 0.5 discrete, elongated mechanosensitive fields of innervation aligned parallel to circular muscle bundles (length = 62 ± 16 mm, n = 10). Anterogradely labeled rectal nerve axons typically passed through sparse irregular myenteric ganglia adjacent to the IAS, before ending in extensive varicose arrays within the circular muscle and, to a lesser extent, the longitudinal muscle overlying the IAS. Few (8%) IAS myenteric ganglia contained intraganglionic laminar endings. In eight preparations, mechanotransduction sites were mapped in combination with successful anterograde fills. Mechanotransduction sites were strongly associated with extensive fine varicose arrays within the circular muscle (P < 0.05), and not with any other neural structures. Conclusions & Inferences Mechanotransduction sites for low‐threshold, slowly adapting mechanoreceptors innervating the IAS are likely to correspond to extensive fine varicose arrays within the circular muscle.     

Anorectal function in patients with collagenous colitis in active and clinically quiescent phase,in comparison with healthy controls

Background Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC. Methods Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re‐assessed. Key Results All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission. Conclusions & Inferences Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.     

Influence of continuous isobaric rectal distension on gastric emptying and small bowel transit in young healthy women

Patients with slow transit constipation frequently have delayed gastric emptying. In animals rectal distensions inhibit gastrointestinal motility. In healthy volunteers isovolumetric rectal distensions delay upper gut transit. The purpose of this study was to determine the effect of continuous isobaric rectal distension on gastric emptying and oro-cecal transit in young females. Using validated 13C octanoic and lactose-[13C] ureide breath tests gastric half-emptying time and oro-cecal transit time for a meal were measured in 12 volunteers. The tests were repeated in randomized order: during isobaric balloon distension and during sham distension. Isobaric rectal distension was applied using a polyethylene bag connected to a barostat. Intraballoon pressure was kept just below the threshold for the urge sensation. Mean gastric half-emptying time during rectal distension (92.3 +/-5.1 min) was significantly higher than during sham distension (78.8 +/- 4 min; P = 0.015). Mean oro-cecal transit time during rectal distension (391.3 +/-29.1 min) and sham distension (328.8 +/- 38.4 min) were not significantly different. In conclusion, these findings indicate that isobaric rectal distension inhibits gastric emptying, but not small bowel transit in young healthy women. Studies in patients with constipation are indicated.     

Effect of topical anaesthesia on oesophageal sensory and motor function in healthy subjects

Abstract Oesophageal hyperalgesia was demonstrated in the non-cardiac chest pain syndrome and suggests an altered perception of visceral stimuli in these patients. Data on oesophageal sensory function and its pharmacological manipulation, however, are fragmentary.
Using a randomized, double-blind, placebo-controlled, cross-over design, ten healthy male volunteers were manometrically examined for the effects of topical oesophageal anaesthesia with benzocaine 0.75% on (1) oesophageal perception of graded intra-luminal balloon distension, (2) oesophageal compliance and primary motility, and (3) rectal perception of graded intraluminal balloon distension.
It was demonstrated that topical benzocaine significantly increased oesophageal perception thresholds for intraluminal distension (P < 0.03), irrespective of them being correlated to distension volume or distension pressure. The level of first sensation increased from 4.3 ml (SD 2.8) and 24.8 mmHg (SD 9.1) to 7.4 ml (SD 4.4) and 32.1 mmHg (SD 8.3), respectively; pain perception increased from 11.O ml (SD 4.5) and 30.9 mmHg (SD 8.9) to 14.5 ml (SO 5.1) and 38.3 mmHg (SD 10.2), respectively. In contrast, oesophageal compliance, primary oesophageal motility and rectal perception were not altered.
It was concluded that topical anaesthesia decreases visceral sensitivity of the oesophagus to mechanical distension by action on intramural nervous afferents. It does not affect oesophageal motor function, nor does it exert systemic analgesic effects.     

Rectal sensorimotor characteristics in female patients with idiopathic constipation with or without paradoxical sphincter contraction

Patients with chronic constipation fulfilling the Thompson criteria can show paradoxical sphincter contraction. Aim of this study was to evaluate rectal sensorimotor characteristics in patients with constipation with or without paradoxical sphincter contraction. Thirty female patients with chronic constipation and 22 female controls were investigated with anal manometry and rectal barostat. Paradoxical sphincter contraction was shown with manometry as a paradoxical increase of anal pressure during straining. Visceral sensitivity and compliance were tested by intermittent and continuous pressure-controlled distension. Patients were classified according to their sensations and compliance into normal, hypersensitive, reduced compliant, insensitive or excessive compliant rectum. Postprandial rectal response (PRR) and phasic volume events (PVEs) were registered for 1 h after a 600-kCal meal. Paradoxical sphincter contraction was found in 13 (43%) patients. In these patients, rectal sensitivity scores were higher (P = 0.045) than in patients without paradoxical contractions, but rectal compliance was not different. In 90% of patients an abnormal rectal sensitivity or compliance was found: excessively compliant in 35%, reduced compliant in 10%, hypersensitive in 27% and hyposensitive in 17%. Both patients with constipation (11%; P = 0.042) and controls (25%; P = 0.002) exhibited the presence of a postprandial rectal response. This response was not significantly different between idiopathic constipation, paradoxical sphincter contraction and controls. Patients with rectal hypersensitivity had lower response than other patients (P = 0.04). Patients with constipation had fewer basal PVEs compared controls (P = 0.03). Postprandial PVEs increased in both patients (P = 0.014) and controls (P < 0.001). Postprandial rectal response and PVE were not different in patients with or without paradoxical sphincter contraction. A total of 90% of female patients with idiopathic constipation show an abnormality in rectal sensation or compliance. The postprandial rectal response was comparable between patients with constipation and controls, however, PVEs were diminished. Patients with paradoxical sphincter contraction had higher rectal sensitivity but an unaltered compliance and postprandial rectal response. Future trials should investigate whether the classification of rectal abnormalities in patients with constipation has clinical importance.     

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.     

Neuroendocrine and blood pressure responses to rectal distensions in individuals with high and low visceral pain sensitivity

BACKGROUND: The mechanisms of interindividual variations in visceral pain sensitivity remain poorly understood. We characterized the neuroendocrine responses to rectal distensions in healthy individuals with high vs. low rectal pain sensitivity. METHODS: Rectal sensory and pain thresholds were determined, and a series of random painful distensions was carried out. Eighteen subjects were stratified into groups with a low rectal pain threshold ("High Sensitivity" group) vs. a high rectal pain threshold ("Low Sensitivity" group) by median split, and were compared with regard to adrenocorticotropic hormone (ACTH) and cortisol, cardiovascular, and emotional responses. RESULTS: Distensions led to an anticipatory stress response, reflected by elevated baseline anxiety, and increased baseline ACTH and cortisol in both groups. In response to distensions, the "Low Sensitivity" group showed significantly greater ACTH and cortisol concentrations analysis of variance (ANOVA time x group for ACTH: p<.05; for cortisol: p<.01), and elevated diastolic blood pressures (BP) (ANOVA group: p<.01) when compared to the "High Sensitivity" group. CONCLUSIONS: Painful rectal distensions are associated with a pronounced anticipatory stress response, reflected by elevated anxiety and elevated stress hormones. Individuals with high rectal pain sensitivity differ from those with low pain sensitivity in distension-induced hormonal and blood pressure responses, suggesting that neuroendocrine responses may be relevant to the pathophysiology of visceral hyperalgesia.     

Effects of vaginal hysterectomy on anorectal sensorimotor functions--a prospective study

Background While bowel and bladder dysfunction are recognized consequences of a radical hysterectomy, the effects of a simple hysterectomy on anorectal sensorimotor functions, particularly rectal sensation, vary among studies and the effects on rectal compliance remain unknown. Our aims were to prospectively evaluate anorectal sensorimotor functions before and after a hysterectomy. Methods Anal pressures, rectal compliance, capacity, sensation, and bowel symptoms were assessed before, at 2 months, and at 1 year after a simple vaginal hysterectomy for benign indications in 19 patients. Rectal staircase (0–44 mmHg, 4‐mmHg steps), ramp (0–200 mL at 50, 200 and 600 mL min^?1) and phasic distentions (8, 16, and 24 mmHg above operating pressure) were performed. Key Results Anal resting (63 ± 4 before, 56 ± 4 mmHg after) and squeeze pressures (124 ± 12 before, 124 ± 12 mmHg after), rectal compliance and capacity (285 ± 12 before, 290 ± 11 mL 1 year after), and perception of phasic distentions were not different before vs after a hysterectomy. Sensory thresholds for first sensation and the desire to defecate were also not different, but pressure and volume thresholds for urgency were somewhat greater (Hazard ratio = 0.7, 95% CI [0.5, 1.0]) 1 year after (vs before) a hysterectomy. Rectal pressures were higher (P < 0.0001) during fast compared with slow ramp distention; this rate effect was greater at 1 year after a hysterectomy, particularly at 100 mL (P = 0.04). Conclusions & Inferences A simple vaginal hysterectomy has relatively modest effects (i.e., somewhat reduced rectal urgency and increased stiffness during rapid distention) on rectal sensorimotor functions.