Intraluminal modulation of gastric sensitivity to distension: effects of hydrochloric acid and meal

Conscious sensations in response to gut distensions may be modulated by temporospatial interactions among different stimuli. This study investigated whether symptoms induced by gastric distension may be modified by hydrochloric acid (HCl) gastric infusion and meal ingestion. In nine healthy subjects, fixed pressure (isobaric) and fixed volume (isovolumetric) distensions were performed during continuous (4 ml/min) intragastric saline or HCl infusion, during fasting and after meal ingestion, until the maximal distension step defined as discomfort or a predefined maximal volume. During fasting isobaric distensions, the maximal distension step was significantly decreased during HCl compared with saline. The intragastric volumes were not significantly different, but the wall tension was significantly lower during HCl than saline. HCl increased gastric compliance. Meal ingestion relaxed the stomach and decreased the pressure at the maximal distension step during saline, but HCl did not further decrease it compared with fasting. During isovolumetric distensions, HCl also increased gastric compliance, but in both fasted and fed states it did not modify the maximal distension steps. In conclusion, sensations in response to gastric isobaric distensions, but not to isovolumetric distensions, are influenced by gastric acid infusion and meal ingestion. The effects of HCl might be related to a sensitization of mucosal mechanoreceptors.     

Rectal and colonic distension elicit viscerovisceral reflexes in humans

Colonic transit is slowed in patients with disordered rectal evacuation, but the mechanism of this phenomenon is unclear. Our objective was to investigate rectocolonic inhibitory reflexes in humans to provide potential insight into patients with obstructed defecation. In 30 healthy subjects, a barostat-manometric assembly recorded colonic tone and phasic activity in the descending colon during rectal distension and recorded rectal tone during colonic distension. Phasic distensions were 8, 16, and 32 mmHg above balloon operating pressure, and staircase inflations were comprised of balloon inflation then deflation in 2-mmHg increments at 30-s intervals from 0 to 36 mmHg. Colonic balloon volumes increased to a similar extent during phasic rectal distensions 8, 16, and 32 mmHg above operating pressure, reflecting reduced colonic tone; balloon volumes also increased and phasic pressure activity decreased during staircase rectal distensions. In contrast, rectal balloon volume declined, reflecting increased tone during phasic and staircase colonic distensions. Thus rectal distension inhibited colonic motor activity, indicative of a viscerovisceral inhibitory reflex.     

Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation

BACKGROUND AND AIMS: the neural mechanisms of distension-induced esophagoupper esophageal sphincter (UES) reflexes have not been explored in humans. We investigated the modulation of these reflexes by mucosal anesthesia, acid exposure, and GABA(B) receptor activation. In 55 healthy human subjects, UES responses to rapid esophageal air insufflation and slow balloon distension were examined before and after pretreatment with 15 ml of topical esophageal lidocaine, esophageal HCl infusion, and baclofen 40 mg given orally. In response to rapid esophageal distension, UES can variably relax or contract. Following a mucosal blockade by topical lidocaine, the likelihood of a UES relaxation response was reduced by 11% (P < 0.01) and the likelihood of a UES contractile response was increased by 14% (P < 0.001) without alteration in the overall UES response rate. The UES contractile response to rapid esophageal air insufflation was also increased by 8% (P < 0.05) following sensitization by prior mucosal acid exposure. The UES contractile response, elicited by balloon distension, was regionally dependent (P < 0.05) (more frequent and of higher amplitude with proximal esophageal distension), and the response was attenuated by topical lidocaine (P < 0.05). Baclofen (40 mg po) had no effect on these UES reflexes. Abrupt gaseous esophageal distension activates simultaneously both excitatory and inhibitory pathways to the UES. Partial blockade of the mucosal mechanosensitive receptors permits an enhanced UES contractile response mediated by deeper esophageal mechanoreceptors. Activation of acid-sensitive esophageal mucosal chemoreceptors upregulates the UES contractile response, suggestive of a protective mechanism.     

Modulatory influences on antegrade and retrograde tonic reflexes in the colon and rectum

Tonic reflexes in the colon and rectum are likely to be important in health and in disorders of gastrointestinal function. The aim of this study was to evaluate the fasting and postprandial "colorectal" and "rectocolic" reflexes in response to 2-min isobaric distensions of the colon and rectum, accounting for enteric sensation, compliance, and distending balloon volume. In 14 healthy fasting subjects, a dual barostat assembly was positioned (descending colon and rectum). A 2-min phasic distension was performed in the colon and rectum in random order while the opposing balloon volume was recorded. Sensation (phasic distension) and compliance (ramp distension) were also determined. The experiment was repeated postprandially. Colonic distension resulted in significant rectal tonic contraction in the fasting (rectal volume change: -35.4 +/- 8.4 ml, P < 0.01) and postprandial (-22.2 +/- 8.4 ml, P < 0.01) states. After adjustment for colonic sensitivity, for compliance, and for distending balloon volume, the rectal volume change remained significant; the extent of the tonic response, however, correlated significantly with increasing pain score (P < 0.01). In contrast, rectal distension did not produce a significant tonic response in the colon (fasting: -6.5 +/- 7.3 ml; postprandial: 2.7 +/- 7.3 ml), either unadjusted or adjusted for rectal sensitivity, compliance, and distending balloon volume. In conclusion, the colorectal reflex, but not the rectocolic reflex, can be readily demonstrated both before and after a meal in response to a 2-min isobaric distension in the colon and rectum, respectively. Although the presence of the colorectal reflex does not depend on colonic sensitivity or the volume of the distending colonic balloon, these factors modulate the reflex, especially in the fasting state.     

Pharmacological analysis of components of the change in transmural potential difference evoked by distension of rat proximal small intestine in vivo

The reflex response to distension of the small intestine in vivo is complex and not well understood. The aim of this study was to characterize the neural mechanisms contributing to the complex time course of the intestinal secretory response to distension. Transmucosal potential difference (PD) was used as a marker for mucosal chloride secretion, which reflects the activity of the secretomotor neurons. Graded distensions (5, 10, and 20 mmHg) of distal rat duodenum with saline for 5 min induced a biphasic PD response with an initial peak (rapid response) followed by a plateau (sustained response). The rapid response was significantly reduced by the neural blockers tetrodotoxin and lidocaine (given serosally) and by intravenous (iv) administration of the ganglionic blocker hexamethonium and the NK(1) receptor antagonist SR-140333. Serosal TTX and iv SR-140333 significantly reduced the sustained response, which was also reduced by the NK(3) receptor antagonist talnetant and by the vasoactive intestinal polypeptide (VPAC) receptor antagonist [4Cl-d-Phe(6), Leu(17)]-VIP. Serosal lidocaine and iv hexamethonium had no significant effect on this component. Inhibition of nitric oxide synthase had no effect on any of the components of the PD response to distension. The PD response to distension thus seems to consist of two components, a rapidly activating and adapting component operating via nicotinic transmission and NK(1) receptors, and a slow component operating via VIP-ergic transmission and involving both NK(1) and NK(3) receptors.     

Mechanisms of reflexes induced by esophageal distension

We investigated the mechanisms of esophageal distension-induced reflexes in decerebrate cats. Slow air esophageal distension activated esophago-upper esophageal sphincter (UES) contractile reflex (EUCR) and secondary peristalsis (2P). Rapid air distension activated esophago-UES relaxation reflex (EURR), esophago-glottal closure reflex (EGCR), esophago-hyoid distraction reflex (EHDR), and esophago-esophagus contraction reflex (EECR). Longitudinal esophageal stretch did not activate these reflexes. Magnitude and timing of EUCR were related to 2P but not injected air volume. Cervical esophagus transection did not affect the threshold of any reflex. Bolus diversion prevented swallow-related esophageal peristalsis. Lidocaine or capsaicin esophageal perfusion, esophageal mucosal layer removal, or intravenous baclofen blocked or inhibited EURR, EGCR, EHDR, and EECR but not EUCR or 2P. Thoracic vagotomy blocked all reflexes. These six reflexes can be activated by esophageal distension, and they occur in two sets depending on inflation rate rather than volume. EUCR was independent of 2P, but 2P activated EUCR; therefore, EUCR may help prevent reflux during peristalsis. All esophageal peristalsis may be secondary to esophageal stimulation in the cat. EURR, EHDR, EGCR, and EECR may contribute to belching and are probably mediated by capsaicin-sensitive, rapidly adapting mucosal mechanoreceptors. GABA-B receptors also inhibit these reflexes. EUCR and 2P are probably mediated by slowly adapting muscular mechanoreceptors. All six reflexes are mediated by vagal afferent fibers.     

Demonstration of mucous mechanoreceptors in the lower esophageal sphincter. Comparison with muscle mechanoreceptors

In anaesthetized cats, vagal unitary discharges originating from the Lower Oesophageal Sphincter (L.O.S.) were recorded in nodose ganglia by means of glass microelectrodes. Numerous mechanoreceptors located both in mucosa and muscular layers were found in L.O.S. The mucus mechanoreceptors (high threshold receptors) were activated by strong compressions and distensions, by rapid passage of liquid through the oesophagus and by striking the mucosa. The muscular mechanoreceptors (low threshold receptors) responded to contraction and distension of L.O.S. Both receptors were connected to nonmyelinated fibres (conduction velocity: 0.9-1.4 m/sec).     

Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a "biological hallmark" for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. These methods have provided further insight into alterations in pain processing in IBS, although the most optimal method and condition remain to be established. In an attempt to give an overview of these methods, a literature search in the electronic databases PubMed and MEDLINE was executed using the search terms "assessment of visceral pain/visceral nociception/visceral hypersensitivity" and "irritable bowel syndrome." Both original articles and review articles were considered for data extraction. This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.     

Effects of a kappa-opioid agonist,asimadoline, on satiation and GI motor and sensory functions in humans

To compare the effects of the kappa-opioid agonist asimadoline and placebo on visceral sensation and gastrointestinal (GI) motor functions in humans, 91 healthy participants were randomized in a double-blind fashion to 0.15, 0.5, or 1.5 mg of asimadoline or placebo orally twice a day for 9 days. We assessed satiation (nutrient drink test), colonic compliance, tone, perception of colonic distension (barostat), and whole gut transit (scintigraphy). Treatment effect was assessed by analysis of covariance. Asimadoline increased nutrient drink intake (P = 0.03). Asimadoline decreased colonic tone during fasting (P = 0.03) without affecting postprandial colonic contraction, compliance, or transit. Gas scores in response to colonic distension were decreased with 0.5 mg of asimadoline at low levels (8 mmHg above operating pressure) of distension (P = 0.04) but not at higher levels of distension. Asimadoline at 1.5 mg increased gas scores at 16 mmHg of distension (P = 0.03) and pain scores at distensions of 8 and 16 mmHg (P = 0.003 and 0.03, respectively) but not at higher levels of distension. Further studies of this compound in diseases with altered satiation or visceral sensation are warranted.     

Changes in the RIII response of the flexion reflex with painful maneuvers

In the search for reliable indirect indices of pain sensation, interest has recently focused on the nociceptive flexion reflex and late components of the brain evoked potentials. In ten volunteers with sciatica, the nociceptive flexion reflex (RIII) and the late component (N150-P220) of the evoked potentials were recorded, with the subjects at rest and during pain produced by the Lasegue manoeuvre. In recordings with the subjects at rest, both responses were stable. During the Lasegue manoeuvre, the RIII response was markedly suppressed, with a mean reduction in area of 40% (P less than 0.001). In contrast, the amplitude of the N150-P220 components did not change significantly. Our results indicate that, of the two parameters tested, RIII alone is a reliable index for measuring pain sensation.     

Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome

In irritable bowel syndrome (IBS) patients, the relationship between sex and sensitivity to visceral stimuli is incompletely understood. Our aim was to evaluate the effect of sex on perceptual responses to visceral stimulation in IBS. Fifty-eight IBS patients (mean age 42+/-1 yr; 34 men, 24 women) and 26 healthy controls (mean age 38+/-3 yr; 9 men, 17 women) underwent barostat-assisted distensions of the rectum and sigmoid colon. Rectal discomfort thresholds were measured using a randomized, phasic distension paradigm before and after repeated noxious sigmoid stimulation (SIG, 60-mmHg pulses). Sex had a significant effect on rectal discomfort thresholds. Women with IBS were the most sensitive (lower thresholds [27+/-2.7 mmHg] and higher ratings), with significantly lower rectal discomfort thresholds compared with men with IBS (38+/-2.3 mmHg) and healthy women who were the least sensitive (41.9+/-3.2 mmHg; both P<0.01). There were no significant differences in rectal discomfort thresholds between healthy men (34+/-4.3 mmHg) and men with IBS. Across both IBS and control groups, women demonstrated a significant lowering of discomfort thresholds after noxious sigmoid stimulation (P<0.01), while men did not. Sex significantly influences perceptual sensitivity to rectosigmoid distension. Women show greater perceptual responses to this paradigm.     

Effects of nutrients and serotonin 5-HT3 antagonism on symptoms evoked by distal gastric distension in humans

Distal gastric distension may contribute to meal-related dyspeptic symptoms. This study's aims were to determine the effects of distinct nutrient classes on symptoms induced by distal gastric distension and their dependence on 5-hydroxytryptamine(3) (5-HT3) receptors. Nine healthy subjects rated pain, nausea, and bloating induced by isobaric distal gastric distensions (6-24 mmHg) during duodenal lipid, carbohydrate, protein, or saline perfusion after treatment with placebo or the 5-HT3 receptor antagonist granisetron (10 microg/kg iv). Distensions produced greater pain, nausea, and bloating with lipid at 1.5 kcal/min compared with saline (P < or = 0.02), primarily because of greater distal gastric volumes at each distending pressure. In contrast, carbohydrate and protein had no significant effect. At 3 kcal/min, lipid increased symptoms through a volume-independent as well as a volume-dependent effect. Granisetron did not affect symptom perception or gastric pressure-volume relationships. In conclusion, isobaric distal gastric distension produces more intense symptoms during duodenal lipid compared with saline perfusion. Symptom perception during distal gastric distension is unaffected by 5-HT3 receptor antagonism.     

Viscerosensory-cardiovascular reflexes: altered baroreflex sensitivity in irritable bowel syndrome

Animal studies have demonstrated that visceral afferent stimulation alters autonomic cardiovascular reflexes. This mechanism might play an important role in the pathophysiology of conditions associated with visceral hypersensitivity, such as irritable bowel syndrome (IBS). As such, studies in humans are lacking, we measured viscerosensory-cardiovascular reflex interactions in IBS patients and healthy controls. Systolic blood pressure (SBP), heart rate (HR), and arterial baroreflex sensitivity (BRS) were studied in 87 IBS patients and 36 healthy controls under baseline conditions and during mild (15 mmHg) and intense (35 mmHg) visceral stimulation by rectal balloon distension. BRS was computed from continuous ECG and arterial blood pressure signals (Finapres-method) during 5-min periods of 15-min metronome respiration. Baseline SBP and HR were not different between patients and controls. In both groups, SBP increased similarly during rectal stimulation, whereas HR decreased during mild and increased intense stimulation. BRS was significantly higher in patients compared with controls at baseline (7.9 +/- 5.4 vs. 5.7 +/- 3.7 ms/mmHg, P = 0.03) and increased significantly in both groups during mild stimulation. This increase persisted in controls during intense stimulation, but BRS returned to baseline in patients. BRS was not significantly different between groups during rectal distension. This study demonstrates the presence of a viscerosensory-cardiovascular reflex in healthy individuals and in IBS patients. The increased BRS in IBS patients at baseline may either be a training-effect (frequent challenging of the reflex) or reflects altered viscerosensory processing at the nucleus tractus solitarii.     

Attenuation of the colorectal tonic reflex in female patients with irritable bowel syndrome

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.     

Neurophysiological evaluation of healthy human anorectal sensation

Patients with functional gastrointestinal disorders often demonstrate abnormal visceral sensation. Currently, rectal sensation is assessed by manual balloon distension or barostat. However, neither test is adaptable for use in the neurophysiological characterization of visceral afferent pathways by sensory evoked potentials. The aim of this study was to assess the reproducibility and quality of sensation evoked by electrical stimulation (ES) and rapid balloon distension (RBD) in the anorectum and to apply the optimum stimulus to examine the visceral afferent pathway with rectal evoked potentials. Healthy subjects (n = 8, median age 33 yr) were studied on three separate occasions. Variability, tolerance, and stimulus characteristics were assessed with each technique. Overall ES consistently invoked pain and was chosen for measuring rectal evoked potential whereas RBD in all cases induced the strong urge to defecate. Rectal intraclass correlation coefficient (ICC) for ES and RBD (0.82 and 0.72, respectively) demonstrated good reproducibility at pain/maximum tolerated volume but not at sensory threshold. Only sphincter ICC for ES at pain showed acceptable between-study reproducibility (ICC 0.79). Within studies ICC was good (>0.6) for anorectal ES and RBD at both levels of sensation. All subjects reported significantly more unpleasantness during RBD than ES (P < 0.01). This study demonstrates that ES and RBD are similarly reproducible. However, the sensations experienced with each technique differed markedly, probably reflecting differences in peripheral and/or central processing of the sensory input. This is of relevance in interpreting findings of neuroimaging studies of anorectal sensation and may provide insight into the physiological characteristics of visceral afferent pathways in health and disease.     

Water deprivation increases Fos expression in hypothalamic corticotropin-releasing factor neurons induced by right atrial distension in awake rats

Atrial mechanoreceptors, sensitive to stretch, contribute in regulating heart rate and intravascular volume. The information from those receptors reaches the nucleus tractus solitarius and then the paraventricular nucleus (PVN), known to have a crucial role in the regulation of cardiovascular function. Neurons in the PVN synthesize CRF, AVP, and oxytocin (OT). Stimulation of atrial mechanoreceptors was performed in awake rats implanted with a balloon at the junction of the superior vena cava and right atrium. Plasma ACTH, AVP, and OT concentrations and Fos, CRF, AVP, and OT immunolabeling in the PVN were determined after balloon inflation in hydrated and water-deprived rats. The distension of the balloon increased the plasma ACTH concentrations, which were higher in water-deprived than in hydrated rats (P < 0.05). In addition, the distension in the water-deprived group decreased plasma AVP concentrations (P < 0.05), compared with the respective control group. The distension increased the number of Fos- and double-labeled Fos/CRF neurons in the parvocellular PVN, which was higher in the water-deprived than in the hydrated group (P < 0.01). There was no difference in the Fos expression in magnocellular PVN neurons after distension in hydrated and water-deprived groups, compared with respective controls. In conclusion, parvocellular CRF neurons showed an increase of Fos expression induced by stimulation of right atrial mechanoreceptors, suggesting that CRF participates in the cardiovascular reflex adjustments elicited by volume loading. Activation of CRF neurons in the PVN by cardiovascular reflex is affected by osmotic stimulation.     

Antinociceptive effect of VSL#3 on visceral hypersensitivity in a rat model of irritable bowel syndrome: a possible action through nitric oxide pathway and enhance barrier function

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel function. There are increasing evidences suggested that VSL#3 probiotics therapy has been recognized as an effective method to relieve IBS-induced symptoms. The aim of this study was to examine the effects of VSL#3 probiotics on visceral hypersensitivity (VH), nitric oxide (NO), fecal character, colonic epithelium permeability, and tight junction protein expression. IBS model was induced by intracolonic instillation of 4% acetic acid and restraint stress in rats. After subsidence of inflammation on the seventh experimental day, the rats were subjected to rectal distension, and then the abdominal withdrawal reflex and the number of fecal output were measured, respectively. Also, colonic permeability to Evans blue was measured in vivo, and tight junction protein expression was studied by immunohistochemistry and immunoblotting method. Rats had been pretreated with VSL#3 or aminoguanidine (NOS inhibitor) or VSL#3+ aminoguanidine before measurements. The rats at placebo group showed hypersensitive response to rectal distension (P < 0.05) and defecated more stools than control rats (P < 0.05), whereas VSL#3 treatment significantly attenuated VH and effectively reduced defecation. Aminoguanidine reduced the protective effects of VSL#3 on VH. A pronounced increase in epithelial permeability and decreased expression of tight junction proteins (occludin, ZO-1) in placebo group were prevented by VSL#3, but not aminoguanidine. VSL#3 treatment reduce the hypersensitivity, defecation, colonic permeability and increase the expression of tight junction proteins (occludin, ZO-1). As the part of this effect was lowered by NOS inhibitor, NO might play a role in the protective effect of VSL#3 to some extent.     

Rectal sensorimotor dysfunction in women with fecal incontinence

The rate and pattern of rectal distension affect rectal distensibility, perception, and anal relaxation in health. Because rectal urgency is a prominent symptom in fecal incontinence (FI), we assessed rectal distensibility, contractions, perception, and anal pressures during rectal distention in 21 healthy, asymptomatic women (age 61 +/- 2 yr, mean +/- SE) and 51 women with FI (60 +/- 2 yr). Rectal staircases (0-32 mmHg, 4-mm steps) and ramp distensions [0-200 ml at 25, 50, and 100 ml/min with a phase of sustained distension (SD), lasting 1 min, between inflation and deflation]. The rectum was stiffer during rapid than slow ramp distention. This effect was more prominent at a lower volume (50 ml) and was also more pronounced in older subjects and in FI. A rectal contractile response was observed not only during inflation but also during SD and during deflation. During inflation, this contractile response was rate dependent in controls but not in FI. During staircase but not ramp distentions, the threshold for the desire to defecate was lower in FI. During ramp distentions, the duration of perception was significantly longer in FI. The rate of distention did not affect rectal perception (i.e., sensory thresholds or duration of perception) during ramp distentions. Baseline anal pressures and the magnitude of anal relaxation during rectal distention were also reduced in FI. In addition to reduced rectal capacity and compliance, women with FI had an exaggerated rate-dependent reduction in rectal distensibility, lower sensory thresholds, and more prolonged perception, indicative of rectoanal dysfunctions.     

TNBS-induced inflammation modulates the function of one class of low-threshold rectal mechanoreceptors in the guinea pig

The effects of trinitrobenzene sulfonic acid (TNBS)-induced inflammation on specialized, low-threshold, slowly adapting rectal mechanoreceptors were investigated in the guinea pig. Under isoflurane anesthesia, 300 microl saline or TNBS (15 mg/ml) in 30% ethanol was instilled 7 cm from the anal sphincter. Six or 30 days later, single unit extracellular recordings were made from rectal nerve trunks in flat-sheet in vitro preparations attached to a mechanical tissue stretcher. TNBS treatment caused macroscopic ulceration of the rectal mucosa at 6 days, which fully resolved by 30 days. Muscle contractility was unaffected by TNBS treatment. At 6 days posttreatment, responses of low-threshold rectal mechanoreceptors to circumferential stretch were increased, and the proportion of afferents responding with von Frey hair thresholds 相似文献   

Changes of the neuropeptides content and gene expression in spinal cord and dorsal root ganglion after noxious colorectal distension

Visceral pain/hypersensitivity is a cardinal symptom of functional gastrointestinal disorders. With their peripheral and central (spinal) projections, sensory neurons in the dorsal root ganglia (DRG) are the "gateway" for painful signals emanating from both somatic and visceral structures. In contrast to somatic pain, the neurochemical pathways involved in visceral pain/hypersensitivity have not been well studied. We hypothesized the neuropeptide changes in spinal cord and DRG during visceral pain would mirror similar changes in somatic nociception. Noxious (painful) colorectal distension (CRD) was done by distending a rectal balloon up to 60 mm Hg phasically for 1 h in Sprague-Dawley rats. The spinal content of calcitonin gene-related peptide (CGRP), substance P (SP), galanin and vasoactive intestinal peptide (VIP) as well as their mRNAs in DRG were measured at 0, 4 and 24 h after the CRD. Visceromotor reflex (VMR) was measured by recording the electromyogram at the abdominal muscle in response to CRD. Distal colorectum was removed for evaluating the presence of inflammation. No significant evidence of histological inflammation was seen in the colonic mucosa/submucosa after repeated CRD, which is confirmed by myeloperoxidase assay. The spinal content of CGRP and SP decreased significantly 4 h after CRD, while galanin and VIP levels increased gradually and reached highest level at 24 h (p<0.05). The mRNAs in DRG of the neuropeptides were significantly upregulated after CRD (p<0.05). VMR recording showed the rat's colon became hypersensitive 4 h after CRD, a sequence parallel to the spinal changes of CGRP and SP in timeframe. Noxious mechanical distension of the colorectum causes an acute change in the spinal levels of excitatory neurotransmitters (CGRP and SP), probably reflecting central release of these peptides from sensory neurons and contributing to the hypersensitivity following the noxious CRD. This is followed by a slower change in the levels of the inhibitory neurotransmitter galanin and VIP. Such stimulation results in significant alternation of the gene expression in DRG, reflecting the plasticity of the neuronal response. In the absence of visceral inflammation, the aforementioned neuropeptides are important mediators in the processing of visceral pain/hypersensitivity.