T1443 Mechanoreceptors Innervating the External Anal Sphincter of the Guinea Pig Penny Lynn, Marcello Costa, Simon Brookes Sensory nerves to the external anal sphincter (EAS) contribute to continence and normal defecation, yet surprisingly little is known about their function. Here we investigated the function of mechanoreceptors to the guinea pig EAS. Methods. Extracellular recordings In Vitro from pudendal nerve branches to the EAS from 9 preparations, combined with anterog- rade labelling of nerve trunks from 4 preparations, were used to characterise extrinsic primary afferent nerve endings activated by circumferential distension (Lynn et al, Gastro. 125(3):786). Results. Of 12 afferents recorded from pudendal nerve, 7 were silent under basal conditions but responded to circumferential stretch with slowly-adapting, low-threshold responses that increased linearly with increased stretch (R 2 0.7, p<0.01). 6/7 slowly-adapting afferents showed significant adaption after 30 s (p<0.01). When probed with von Frey hairs, they had low thresholds (0.1-0.5 mN) and responded linearly to increased pressure (n=4, R 2 = 0.4, p<0.01). The other 5 pudendal afferents were silent under basal conditions and responded to circumferential stretch with phasic responses at the onset and offset of a maintained stretch. There was no relationship in firing rate with the degree of stretch (R 2 <0.1, p=0.2). During graded increase in stretch, vibrations from the stepper motor typically evoked rapid firing; evoked peak instantaneous frequency inversely related to rate of stretch (n=3, R 2 =0.45, p<0.05). When probed with von Frey hairs, they had low thresholds (0.1- 0.2mN), and typically one mechanotransduction site. Responses to von Frey hairs were phasic, and peak instantaneous frequency was unrelated to the degree of compression (n= 3, R 2 =0.1, p=0.2). Anterograde labelling of extrinsic nerves showed that filled axons typically course over the surface of the muscle before entering the EAS musculature. Filled axons were predominantly flattened axons, but not varicose. They end either as varicose arrays within the muscle aligned circularly, or as flattened bifurcated endings within the circular muscle. No cell bodies were observed. Conclusions. The external anal sphincter has two functional classes of mechanoreceptors; slowly-adapting low-threshold mechanoreceptors and phasic low-threshold mechanoreceptors. From previous studies (Lynn et al, Gastro. 125(3):786, Lynn et al, Gastro 132(4 suppl 2):A872) the EAS receives different sensory innervation compared to the rectum and internal anal sphincter, presumably related to differences in physiological control of the regions. T1444 Dose Response Evaluation and Reliability of the Oral Capsaicin Capsule Test in Healthy Subjects Martina Führer, Johann Hammer Introduction: Open-labelled trials have suggested that intragastric capsaicin application induces painful and non painful upper gastrointestinal sensations in healthy subjects and significantly higher symptom scores in patients with functional dyspepsia. Aim: to study dose-response and reliability of the oral capsaicin capsule test in a double blind trial in healthy subjects Methods: N= 20 healthy subjects (10 male, 10 female, age range: 19 to 56 years) swallowed identical capsules containing 0 mg, 0.25 mg, and 0.75 mg capsaicin on four different days, each 1 week apart, double blinded and in random order. The 0.75mg capsule was ingested twice. Before and 30 minutes after ingestion of the capsule subjects filled out a graded questionnaire evaluating the severity of 9 symptoms by 5 grades: (1) sensation of abdominal pressure or fullness,(2) sensation of cramps or colics, (3) stinging or sharp sensation, (4) nausea, (5) heartburn, (6) flutter-like sensation, (7) warmth, (8) sensation of vacuum and (9) pain. Score differences before and after swallowing the capsules were calculated. Data are given as mean± SEM. Results: After placebo (0 mg) symptom scores were 0.5± 0.7 (p<0,001 vs. 0.75mg), after 0.25 mg capsaicin 2.3±1.8 (p=0.01 vs. 0.75mg) and after the first capsule containing 0.75 mg capsaicin symptom scores were 5.7±4.0. There was no significant difference between symptom scores after the first and second 0.75 mg capsaicin capsule (2nd: 6.0± 4.8; p=0.86 vs. 1st capsule). After ingestion of 0.75 mg capsules, feeling of warmth (1.4± 1.0), pain (0.6± 0.1), pressure (0.9± 1.0) and nausea (0.9± 0.9) were the symptoms that were reported as most intense. Conclusion: The capsaicin capsule test is reliable and dose dependently induces upper gastrointestinal symptoms. The capsaicin capsule test might be a useful tool in the diagnostic work-up of patients with functional gastrointestinal disorders. T1445 Is Visceral Hypersensitivity in Irritable Bowel Syndrome Due to Sensitisation of Pain-Selective or Multimodal Afferent Pathways? Jenny Gunnarsson, Iris Posserud, Jan F. Tack, Hasse Abrahamsson, Magnus Simren Background: A subgroup of patients with irritable bowel syndrome (IBS) is hypersensitive to rectal distension. These patients have more severe pain (Posserud et al Gastroenterology 2007), indirectly suggesting hyperalgesia. Whether this is due to activation of pain specific afferent pathways or multimodal afferent pathways also mediating non-painful sensations is unknown. In patients with functional dyspepsia and visceral hyperalgesia indirect evidence has been found favouring activation of multimodal afferent pathways rather than an isolated upregulation of pain specific afferents (Vandenberghe et al Gut 2005). Aim: To evaluate whether hypersensitive IBS patients in addition to hyperalgesia have more intense non- painful sensations during rectal stimulation, indicating involvement of multimodal afferent pathways. Methods: We included 227 patients with IBS meeting the Rome II criteria (mean age 38 years; 168 females). They underwent rectal balloon distensions, with stepwise incre- ments of 5 mm Hg until pain was reported or a pressure of 70mmHg was reached. Sensory thresholds were determined, and the patients reported the intensity of pain and non-painful sensations on a visual analogue scale (VAS) during each pressure step. Rectal hypersensitivity was defined as a pain threshold ≤31 mm Hg (the fifth percentile in healthy controls). Results: Sixty-three (28 %) patients were hypersensitive to rectal balloon distensions. Compared with the normosensitive patients the hypersensitive patients had lower pressure thresholds for all the sensations studied: first sensation (12±3 vs. 16±5 mmHg (mean±SD); p<0.001), defecatory urge (16±4 vs. 23±8 mmHg; p<0.001), discomfort (20±5 vs. 33±10 mmHg; A-557 AGA Abstracts p<0.001) and pain (26±4 vs 47±11 mmHg; p<0.001). The hypersensitive patients reported more intense non-painful sensations compared with the normosensitive patients at any given balloon pressure. At pressures of 5, 10, 15 and 20 mm Hg above the minimal distending balloon pressure, the VAS for non-painful sensations were 25±20 vs. 10±12 mm, 45±26 vs. 21±17mm, 52±20 vs. 29±21mm and 65±18 vs. 39±24mm respectively (all p<0.0001). At the maximal distending pressure (pain threshold) similar intensity of non-painful sensa- tions was reported in the two groups (69±19 vs. 69±20mm; NS), whereas more intense pain was perceived in the hypersensitive group (42±22 vs. 30±22mm; p<0.001). The hyper- sensitive patients were younger (33±9 vs. 40±16 years; p<0.0001), but the gender distribution in the groups was similar. Conclusion: Our findings implicate that multimodal afferent pathways and not only the pain specific pathways are implicated in the generation of visceral hypersensitivity in IBS. T1446 The Transient Receptor Potential Vanilloid Type 1 (TRPV1) Receptor Antagonist BCTC Attenuates Colitis-Induced Sensitization of Pelvic Afferent C-Fibers in Anaesthetized Rats Heiko U. De Schepper, Benedicte Y. De Winter, Arnold G. Herman, Paul A. Pelckmans, Joris G. De Man Introduction: Patients with inflammatory bowel disease (IBD) often suffer from gastrointesti- nal sensitivity disorders. This visceral hypersensitivity has also been shown in rat models of IBD, but its pathophysiology remains incompletely understood. We aimed to study the role of transient receptor potential vanilloid type 1 (TRPV1) receptors in the pathogenesis of colitis-induced afferent nerve sensitization. Methods: Distal colitis was induced in female Wistar rats by a colorectal enema of 7.5 mg trinitrobenzene sulphate (TNBS) in 30% ethanol 72 h prior to the experiment. Rats were anaesthetized using pentobarbital (60 mg/kg, i.p.). The pelvic nerve was fitted with a silver electrode for electrical stimulation. A balloon (5 cm) inserted in the colorectum allowed phasic colorectal distensions (CRD, 20 s at 4 min intervals). The lumbosacral spinal cord was exposed and the S1 dorsal root was identified and teased into fine strands. These were individually draped over a bipolar platinum electrode in a liquid paraffin bath (37°C). Fibers responding to CRD were identified and their conduc- tion velocity was calculated from the response time of spinal nerves to pelvic nerve stimulation (0.5 ms pulse, 5-8 V). The effect of increasing i.v. doses of the TRPV1 antagonist BCTC (0.5 and 1 mg/kg, 3 min before subsequent CRD) or its vehicle (hydroxypropyl-β-cyclodex- trin) was tested on the afferent response to repetitive distensions (60 mmHg). Results (table): TNBS colitis had no effect on colorectal compliance, but significantly increased the response of pelvic afferent C-fibers to colorectal distension. BCTC did not significantly affect the C- fiber afferent response to CRD in controls, but normalized the sensitized response of these neurons in rats with colitis (P<0.05). TNBS colitis had no effect on the response to CRD of Aδ-fibers, nor was their activity modulated by BCTC. TNBS colitis increased the spontaneous activity of both C- and Aδ-fibers, an effect which was insensitive to administration of BCTC. Conclusion: TRPV1 signalling mediates the colitis-induced sensitization of pelvic afferent C-fibers to CRD, while pelvic afferent Aδ-fibers are neither sensitized by colitis nor affected by TRPV1 inhibition. Afferent firing rate (Hz) to CRD (60 mmHg) after administration of BCTC. Mean±SEM for n=5-7.*P<0.05, significantly different from controls; #P<0.05, significantly different from vehicle treatment, 2way ANOVA, posthoc SNK. T1447 Gamma Oscillation Reflect the Dysfunctional Visceral Sensory Processing and Modulation in Irritable Bowel Syncrome Satoshi Watanabe, Tomomi Hattori, Motoyori Kanazawa, Michiko Kano, Shin Fukudo Background & Aims: Visceral sensory processing is abnormal in most patients with irritable bowel syndrome (IBS). Although the brain areas involved in processing visceral sensitivity have been identified, the electrical coupling remains largely unknown. The synchronous oscillation of gamma band responses of 30-90 Hz appears to be an appropriate index for measuring neural communication between the brain regions. We examined the hypothesis that IBS patients show abnormalities in gamma oscillation during visceral stimulation and hypnotic modulation. Methods: Electroencephalography (EEG) was recorded from twelve IBS patients and 12 matched healthy controls during electrical stimulation of the rectum. Each electrical stimulation was performed 100 times with an intensity of either 0 mA or 30 mA. The hypnotic suggestions for modulation of pain affect were given before the beginning of each stimulus. Time-frequency analysis was performed on each single trial and compared to baseline. The averaged power of the time-frequency window was calculated and entered into a three-way (group×condition×electrode) analysis of variance. Results: The rectal stimu- lation of the intensity of 30 mA evoked unpleasant or painful visceral perception in all subjects. The rectal stimulation evoked increased event-related synchronization (ERS) of gamma band (40-50 Hz) and theta band (4-7 Hz) power of central regions at 100-300 ms time window. IBS patients exhibited increased ERS of gamma and theta band power at the 100-300 ms time window compared with healthy controls (F[1,22]=34.16, p<0.01; F[1,22]= 10.70, p<0.01). In healthy controls, hypnotic analgesic suggestion induced increased ERS of gamma band power in right frontal and temporal regions at the 500-600 ms time window (F[28,308]=1.66, p<0.05). In IBS patients, analgesic suggestion induced no increased ERS of gamma band power in the frontal regions. Conclusions: These results suggest that neural oscillation of gamma and theta band activity at early time window reflects cortical processing to transfer sensory information from perceptual stages to cognitive stages, and that IBS patients may have an enhancement in communication between distant brain regions, possibly AGA Abstracts