Visceral pain may be influenced by many factors. The aim of this study was to analyze the impact of sex and quality of intracolonic mechanical stimulus on the behavioral manifestations of visceral pain in a preclinical model. Male and female young adult Wistar rats were sedated, and a 5 cm long latex balloon was inserted into the colon. Sedation was reverted and behavior was recorded. The pressure of the intracolonic balloon was gradually increased using a sphygmomanometer. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation. Two different types of stimulation were used: tonic and phasic. Phasic stimulation consisted of repeating several times (3x) the same short stimulus (20 s) within a 5 min interval allowing a 1 min break between individual stimuli. For tonic stimulation the stimulus was maintained throughout the whole 5 min interval. Both phasic and tonic stimulation produced a pressure-dependent increase of abdominal contractions. The abdominal response was more intense under phasic than under tonic stimulation, but with differences depending on the sex of the animals: females exhibited more contractions than males and of similar duration at all pressures, whereas duration of contractions pressure-dependently increased in males. The duration of tonically stimulated contractions was lower and not sex- or pressure-dependent. In the rat, responses to colonic distension depend on the quality of the stimulus, which also produces sex-dependent differences that must be taken into account in the development of models of pathology and visceral pain treatments.

Most individuals with spinal cord injury have neurogenic bowel dysfunction, which includes slowed colonic motility and has a significant impact on their health and quality of life. Bowel management typically includes mechanical rectal distension to evoke a recto-colic reflex and promote bowel emptying. Electrical stimulation could replace this mechanical distension. The purpose of this study was to determine the feasibility of evoking colonic activity using electrical stimulation.

Acute experiments were conducted in eight neural-intact cats under chloralose anesthesia. Patterned electrical stimulation was administered via electrodes placed on the surface of the distal colon or proximal colon. Distal and proximal colon pressures were measured using saline-filled balloon catheters. Outcome measures included peak colonic pressure; time to onset of response; and time to peak pressure compared to baseline without stimulation.

Stimulation elicited colonic activity in all animals. Peak colon pressures were 15 ± 28 cmH₂ O and were proportional to stimulation amplitudes. Time to onset and time to peak pressure were 13 ± 19 s and 37 ± 49 s, respectively, and were not significantly affected by stimulus parameters. Proximal colon stimulation only resulted in pressure responses from the proximal colon, but distal colon stimulation resulted in both proximal and distal responses in 40% of trials. Adding isoflurane anesthesia removed this proximal response to distal stimulation.

Distal colon stimulation evoked colonic activity. The dependence of this response on stimulation location and anesthesia suggests that responses were reflex mediated. Colonic stimulation may have the potential to improve colonic motility for individuals with neurogenic bowel dysfunction.

The rectoanal inhibitory reflex (RAIR) is important in gas and stool evacuation. We examined RAIR features in patients with chronic constipation who exhibited bloating with and without abdominal distension, to determine whether alterations in RAIR may be a factor in the pathogenesis of abdominal distension. Seventy-five female patients with chronic constipation with or without abdominal distension were included in the study. The presence or absence of abdominal distension was assessed according to the Rome II questionnaire. All patients underwent both RAIR and rectal sensitivity testing, and specific RAIR parameters were analyzed. Patients were divided into two groups: abdominal bloating with distension (D, n = 55) and abdominal bloating without distension (ND, n = 20). D had a longer time to the onset of anal sphincter inhibition (latency of inhibition) (P = 0.03) compared with ND. In logistic regression analysis, a combination of age, latency of inhibition and the time measured from onset of inhibition to the point of maximum inhibition predicted abdominal distension (P = 0.002). There were no differences between groups for the time from point of maximum inhibition to recovery and for the percentage of internal anal sphincter relaxation. This is the first study to examine the role of RAIR in patients with abdominal distension. Female patients with constipation and abdominal distension exhibited differences in the temporal characteristics of, but not in the degree of, anal sphincter relaxation compared with patients without distension. Since this study was uncontrolled, further studies are necessary to determine the contribution of altered anorectal reflexes to abdominal distension.

Distention of the proximal colon may have inhibitory or excitatory effects on the rectum and vice versa. The reflexes between the proximal colon and the rectum have not been well studied due to difficulties in accessing the proximal colon. The aim of this study was to investigate the reflex responses and their mechanisms between the proximal colon and the rectum in consideration of distention-related changes in tone and compliance of these regions as well as anal sphincter relaxation in a canine model. Proximal colon/rectal tone, compliance, and anal sphincter relaxation were investigated in six dogs chronically implanted with a proximal colon cannula while in the fasting state and during proximal colon distention or rectal distention. It was found that: 1) both rectal distention and proximal colon distention significantly and substantially decreased the compliance of the opposite regions, and guanethidine abolished proximal colon distention-induced changes in rectal compliance; 2) rectal/proximal colon distension decreased proximal colonic/rectal tone, and guanethidine abolished both of these inhibitory effects; 3) the anal sphincter was more sensitive to rectal distention than proximal colon distention; and 4) the minimal distention pressure required to induce anal inhibitory reflex was lower for rectal distention than proximal colon distention. It was concluded that distention-related changes in tone and compliance suggest the long inhibitory reflexes between the proximal colon and the rectum with the sympathetic involvement in rectal responses. The anal sphincter is more sensitive to the distention of the rectum than that of the proximal colon.

The pathophysiology of IBS is complex and still incompletely known. Both central and peripheral factors are thought to contribute to the symptoms of IBS, including psychosocial factors, abnormal GI motility and secretion, and visceral hypersensitivity. In this review the involvement of peripheral factors in the pathophysiology in IBS is reviewed. Altered GI motility is commonly found in this patient group, even though a specific motor pattern has been hard to find. Colonic transit has been found to be of relevance for the bowel habit of the patient. Abnormal gas handling within the gut is also commonly seen, and seems to be one, but not the only factor responsive for bloating. There is also limited evidence supporting the presence of abnormal GI secretion in IBS, but its relevance for symptoms remains unclear. Visceral hypersensitivity is currently considered to be one of the most important pathophysiological factors in IBS. It can be modulated by several external and internal factors and recent studies support an association between colorectal sensitivity and the symptoms reported by the patients, especially pain.

The role of the central nervous system in enteroenteric motor reflexes remains controversial. Our aims were as follows: 1) to evaluate colorectal, rectocolic, gastrocolonic, and gastrorectal reflex responses in patients with cervical spinal cord injury (SCI) and 2) to compare these responses with those in healthy subjects. In six patients with SCI (5 male, 42 +/- 4 yr) and six healthy control subjects (5 male, 36 +/- 5 yr), 2-min phasic distensions were performed randomly via dual-barostat balloons in the colon and rectum. Continuous colonic and rectal balloon volumes were recorded during distensions and after a 1,000-kcal liquid meal. Mean balloon volumes were recorded before, during, and after phasic distensions and over 60 min postprandially. The colorectal response was similar in control subjects and SCI patients (rectal volume reduction = 28 +/- 11% and 15 +/- 5% in SCI patients and healthy subjects, respectively); the rectocolic response was variable. The gastrocolonic response was present in all subjects (colonic volume reduction = 49 +/- 4% and 44 +/- 3% in SCI patients and healthy subjects, respectively), with a time effect in the first 30 min (P < 0.0001) and a group effect in the second 30 min (P < 0.004). The gastrorectal response was present in four SCI patients and five healthy subjects (rectal volume reduction = 38 +/- 4% and 41 +/- 3% in SCI patients and healthy subjects, respectively), with a time effect in the first 30 min (P < 0.0001) but no group effect in the second 30 min. Intact neural transmission between the spinal cord and higher centers is not essential for normal colorectal motor responses to feeding and distension; however, a degree of central nervous system and neurohormonal modulation of these responses is likely.

Preoperative radiotherapy followed by rectal resection with total mesorectal excision (TME) and colo-anal anastomosis severely compromises anorectal function, which has been attributed to a decrease in neorectal capacity and neorectal compliance. However, to what extent altered motility of the neorectum is involved, is still unknown. The aim of the study was to compare the motor response to (prolonged) filling of the (neo-)rectum in patients after preoperative radiotherapy and rectal resection with that in healthy volunteers (HV).

Neorectal function (J-pouch or side-to-end anastomosis) was studied in 15 patients (median age 61 years, 10 males) 5 months after short-term preoperative radiotherapy (5 x 5 Gy) and rectal resection with TME for rectal cancer and compared with that of 10 volunteers (median age 41 years, 7 males). Furthermore, patients with a colonic J-pouch anastomosis (n=6) were compared with patients with a side-to-end anastomosis (n=9). (Neo-)rectal sensitivity was assessed using a stepwise isovolumetric and isobaric distension protocol. (Neo-)rectal motility was determined during prolonged distension at the threshold of the urge to defecate.

The neorectal volume of patients at the threshold of the urge to defecate (125 +/-45 ml) was significantly lower when compared with that of HV (272+/-87 ml, P<0.05). The pressure threshold, however, did not differ between patients (26+/-9 mm Hg) and HV (21+/-5 mm Hg) and neither did the pressure threshold differ between patients with a J-pouch and those with side-to-end anastomosis. In HV, no rectal contractions were observed during prolonged rectal distension. In contrast, in all 15 patients, prolonged isovolumetric and isobaric distension induced 3 (range 0-5) rectal contractions/10 min, which were associated with an increase in sensation in half of the patients.

Patients who underwent preoperative radiotherapy and rectal resection with TME, but not HV, developed contractions of the neo-rectum in response to prolonged distension. We suggest that this neorectal "irritability" represents a new pathophysiological mechanism contributing to the urgency for defecation after this multimodality treatment.

Motor and sensory dysfunction of the gut are present in a subset of patients with irritable bowel syndrome (IBS). Recent studies have demonstrated the presence of a recto-colonic inhibitory reflex in healthy humans. It is not known whether this reflex exists in IBS. We studied rectal compliance, perception and the recto-colonic reflex by measuring volume responses of the descending colon to rectal distentions by barostat in 26 IBS patients and 13 healthy controls under both fasting and postprandial conditions. In the fasting state, rectal distention inhibited colonic tone and phasic motility to a similar extent in health and IBS. After a meal, rectal distention inhibited colonic tone and phasic motility to a lesser degree (P < 0.05) in IBS than health. Under postprandial but not fasting conditions, rectal distentions of increasing intensity were associated with higher pain scores in IBS than in health. Rectal distention inhibits tonic and phasic motility of the descending colon in healthy controls and in IBS patients. Postprandially this recto-colonic inhibitory reflex is impaired and attenuated in IBS patients compared with controls. These findings point to an altered reflex function in IBS and have implications for pathophysiology and therapy.

The pathogenesis and pathophysiology of irritable bowel syndrome is complex and still incompletely known. Potential pathogenetic factors include genes, infectious events, psychological symptoms and other loosely defined environmental factors. Both alterations at the central and peripheral level are thought to contribute to the symptoms of irritable bowel syndrome, including psychosocial factors, abnormal gastrointestinal motility and secretion, and visceral hypersensitivity. Today irritable bowel syndrome is viewed upon as a disorder of dysregulation of the so-called brain-gut axis, involving abnormal function in the enteric, autonomic and/or central nervous systems, with peripheral abnormalities probably dominating in some patients and disturbed central processing of signals from the periphery in others. Lines of evidence also suggest that inflammation within the gastrointestinal tract may be of great importance in at least subgroups of irritable bowel syndrome patients. To conclude, a complex picture of the pathogenesis and pathophysiology of irritable bowel syndrome is emerging, with interactions between several different alterations resulting in the divergent symptom pattern in these patients.

Alterations in normal intestinointestinal reflexes may be important contributors to the pathophysiology of irritable bowel syndrome (IBS). Our aims were to compare the rectal tonic responses to colonic distension in female IBS patients with predominant constipation (IBS-C) and with predominant diarrhea (IBS-D) to those in healthy females, both fasting and postprandially. Using a dual barostat assembly, 2-min colonic phasic distensions were performed during fasting and postprandially. Rectal tone was recorded before, during, and after the phasic distension. Colonic compliance and colonic sensitivity in response to the distension were also evaluated fasting and postprandially. Eight IBS-C patients, 8 IBS-D patients, and 8 age- and sex-matched healthy subjects (group N) participated. The fasting increments in rectal tone in response to colonic distension in both IBS-C (rectal balloon volume change -4.6 +/- 6.1 ml) and IBS-D (-7.9 +/- 4.9 ml) were significantly reduced compared with group N (-34 +/- 9.7 ml, P = 0.01). Similar findings were observed postprandially (P = 0.02). When adjusted for the colonic compliance of individual subjects, the degree of attenuation in the rectal tonic response in IBS compared with group N was maintained (fasting P = 0.007; postprandial P = 0.03). When adjusted for colonic sensitivity there was a trend for the attenuation in the rectal tonic response in IBS patients compared with group N to be maintained (fasting P = 0.07, postprandial P = 0.08). IBS patients display a definite attenuation of the normal increase in rectal tone in response to colonic distension (colorectal reflex), fasting and postprandially. Alterations in colonic compliance and sensitivity in IBS are not likely to contribute to such attenuation.