T1467 Visceral and Somatic Sensitivity in Patients with Irritable Bowel Syndrome and Coeliac Sprue

AGA Abstracts

T1467

suppress pain from a second heterotopic pain stimulus. Testing DNIC requires administering a phasic, noxious, test stimulus (TS), prior to, and concurrent to administering a tonic noxious conditioning stimulus (CS). The reduction in pain perception of the TS during the CS is identified as the DNIC effect. Aim: To compare DNIC in IBS and healthy controls (HC) by using a somatic TS and a somatic CS while controlling for non-specific effects. Method: Subjects were 48 pre-menopausal females (27 with IBS), mean age of 29 years. The TS was produced by a phasic heat thermode [peak temperature = 50°C, inter-stimulus interval = 3 seconds] applied to the left palm. The CS was submersion of the right hand in painful 12°C water. Reductions in Average Pain Ratings (APR) from the TS during baseline, to the APR of the TS during the CS were compared between IBS patients and HC. In addition, subjects were retested (counter-balanced) using a non-painful CS (hand submersion in 32°C water) to control for non-specific effects. Group differences in psychological and cardiovascular reactivity measures were also assessed to further control for known influences on DNIC scores. Results: IBS subjects demonstrated a smaller DNIC effect than HC (p= 0.011, Repeated Measures ANOVA). IBS subjects also reported significantly greater stress than HC on measures of state anxiety, depression, catastrophizing, and anger-out expression. After controlling for non-specific effects occurring during the non-painful CS (such as distraction and psychological measures), IBS subjects showed further decreases in DNIC (p=0.002). There were no group differences in cardiovascular reactivity, age, body mass index, race, APR, or pain ratings for the 12°C CS. Discussion: These data demonstrated deficient DNIC in IBS. This is the first study to adequately control for alternative explanations of pain reduction during counter-irritation. Only by controlling for non-specific effects can evidence of deficient DNIC be attributed to dysregulation in endogenous analgesic mechanisms. [Supported by NIH R24DK67674]

Visceral and Somatic Sensitivity in Patients with Irritable Bowel Syndrome and Coeliac Sprue Maria Pia Caldarella, Gianpia Affaitati, Mariaelena Serio, Alessandra Fabrizio, Chrysanthi Balatsinou, Antonella Savini, Angelo Milano, Francesco Laterza, Maria Adele Giamberardino, Matteo Neri Background: We have recently demonstrated that patients with irritable bowel syndrome (IBS) show somatic hypersensitivity to stimulation, in particular in areas of abdominal pain referral (Caldarella et al, AJG 2006). In addition, visceral hypersensitivity, which is considered an hallmark of IBS, is also present in patients with untreated coeliac sprue (CS); sensory thresholds in these patients return completely to normal within six months after the beginning of a gluten free diet (GFD, DDW 2007) Aim of this study was to evaluate differences of visceral and somatic sensitivity patterns in patients with IBS, untreated CS and CS after > 12 months of GFD in comparison to health. Materials and Methods: We studied 10 patients with IBS, 9 patients with untreated CS, 5 patients with CS+GFD, and 9 healthy controls. Visceral sensitivity was evaluated by the tensostat, by means of rectal distensions at increasing tension levels of 4 gr steps up to 64 gr or discomfort. Pain thresholds to electrical stimulation were also measured in the skin and underlying subcutis and muscle in visceral pain referral areas and controls sites outside the abdomen (trapezious, deltoid and quadriceps). Results: IBS and untreated CS patients demonstrated rectal hypersensitivity in comparison to treated CS patients and controls. The threshold of discomfort was respectively 40±6 gr in IBS and 36±5 in untreated CS patients, while patients with treated CS and healthy controls tolerated all distensions without discomfort. For the instance of somatic sensitivity, in the areas of pain referral, pain thresholds of all three layers of the body wall were lower than normal in IBS (p<0.001 vs controls). Both untreated and treated CS demonstrated somatic hypersensitivity only in deeper layers, such as subcutis and muscle (p<0,001 vs control; ns vs. IBS). On the contrary, in control areas all patients' groups revealed a similar pattern, consisting of normal pain thresholds in cutis and lower than normal in subcutis and muscle (p<0.001 vs controls). Conclusion: visceral and cutis hypersensitivity in pain referral areas are specific markers of IBS. Somatic hypersensitivity in deep skin layers even beyond resolution of abnormal visceral sensory patterns, may be a consequence of long-lasting abdominal pain receptors stimulation (Sensory scar)

T1470 Rectal Distension Produces Reductions in Celiac and Superior Mesenteric Artery Blood Flow in Anesthetized Rats - a Novel Observation Felix W. Leung Background: Gut ischemia and rectal distension separately being associated with abdominal discomfort (eg dyspepsia, pain) and altered gut motility (eg abnormal transit) have been described. Whether rectal distension can produce reductions in celiac artery (CA) or superior mesenteric artery (SMA) blood flow (gut ischemia) has not been reported. Hypothesis: Rectal distension produces dose-related reductions in CA and SMA blood flow. Method: In anesthetized rats laparotomy provided access to CA or SMA for placement of pulsed Doppler flowmetry probes. Abdominal incision was closed with clips. A 4 cm long latex balloon was placed in the rectum at 1 cm above the anal verge. During control periods CA or SMA blood flow was monitored without balloon inflation (0 ml). During experimental periods balloon was sequentially distended with 2.5, 5 and 7.5 ml of air. Distension was maintained each for 2 min. Balloon was then deflated and monitoring continued for an additional 2 min. Result: Upon distension of the rectal balloon there was an abrupt rise in CA or SMA blood flow. These changes were transient, followed immediately by a fall in these parameters, which remained at sustained reduced levels until the balloon was deflated. Monitored parameters returned to baseline after balloon deflation. The baseline immediately before each distension and trough values of CA or SMA blood flow during distension were recorded. The trough values were expressed as percent change from the respective baseline. All distension volumes significantly reduced blood flow, maximum at 7.5 ml for the CA and 5 ml for the SMA (see Table). Conclusion: The observation of rectal distension producing gut ischemia is novel. The rapid changes suggest involvement of neural reflexes (eg adrenergic and mucosal afferent nerve-related mechanisms). A compartment syndrome (based on fixed intra-abdominal volume) is also a plausible explanation. The sustained reductions reflect gut ischemia during persistent rectal distension. The hypothesis that gut ischemia may offer a novel local explanation for the abdominal discomfort (eg dyspepsia, pain) and altered gut motility (eg abnormal transit) associated with rectal distension (eg balloon, stool in the rectum due to constipation, or gas from gas producing bacteria) deserves to be tested. Effect of rectal distension on CA and SMA blood flow.

T1468 Stimulation of the Medial Thalamus-Anterior Cingulate Cortex Synapses Is Important for Learning and Triggering Pain Memories in Visceral Hypersensitive States Xiaoyin Wu, Jing Fan, Zhijun Cao, Shenliang Chen, Rui Zhang, Min Wang, Chung Owyang, Ying Li We have recently demonstrated that anterior cingulate cortex (ACC) modulates visceral pain in viscerally hypersensitive (VH) rats. Using a VH rat model of colonic anaphylaxis evoked by intraperitoneal injection of chicken egg albumin we showed that VH together with ACC sensitization persisted for at least 2 months even though colonic mucosal inflammation has subsided within the first week. We hypothesize that the persistence of ACC sensitization independent of mucosal inflammation may be mediated by changes in the strength of synapses such as long term potentiation (LTP) in the ACC neural circuits. To test this hypothesis we utilized awake VH rats and measured ACC field potentials elicited by electrical stimulation of the medial thalamic nuclei (MT) which were used as a quantitative measure of synaptic strength. Compared to controls, which showed a maximal response at 12V stimulation, VH rats demonstrated 90% larger response to 6V stimulus indicating enhancement of basal synaptic transmission within the ACC. Theta burst stimulation (TBS) which was used to induce LTP, evoked a peak response of 190±4% of basal compared to 137±5% in control rats (P<0.05). The enhanced LTP lasted for 120 min which was 4x longer than that observed in controls. Enhancement of ACC neuronal firings following TBS in control rats was similar to the increased response of ACC to colorectal distention (CRD) in VH rats. Functional pain studies further confirmed that artificial induction of LTP in the ACC by TBS in normal rats enhanced visceromotor response (VMR) to 20, 40 and 60 mmHg CRD from 1±0.3, 23±3 and 36±5 muscle contractions/5 sec to 8±1, 40±3 and 51±6 contractions/ 5 s following TBS. When TBS was repeated 6 times per day for 3 consecutive days the increase in VMR lasted up to 4 days suggesting that the stimulation of MT-ACC synapses evoked a memory of heightened pain response. Lesioning of ACC erased this “memory” resulting in no increase in VMRs induced by TBS. In separate studies, subthreshold TBS (<6V) had no effect on VMR in control rats; however it evoked a 1.5-2 fold increase in VMRs to CRD in VH rats. This suggests the stimulation of the MT-ACC synapses may retrieve “memory” of prior painful experience resulting in a VH state. As a control TBS applied to the thalamic nucleus submedius (Sm) did not induce LTP in the ACC and failed to enhance subsequent increased VMR to CRD. In conclusion, we have demonstrated that induction and maintenance of LTP in the ACC occurred in VH rats. This is mediated by stimulation and strengthening of the medial thalamus-ACC synapses which appear to be an important mechanism for learning and triggering of pain memories in the VH states.

†vs baseline, paired t; *vs 2.5 ml, repeated measures ANOVA. T1471 Incidence of Complications Associated with Chronic Home Parenteral Nutrition Is Higher in Patients with a Motility Disorder Than Short Bowel Syndrome As Their Underlying Disease John K. Siepler, Thomas G. Diamantidis, Reid A. Nishikawa, Rod J. Okamoto

T1469

Background: Patients unable to tolerate adequate oral nutrition to maintain their body mass may require chronic home parenteral nutrition (HPN). The underlying diseases in these patients are often a motility disorder(MOT) or other reasons such as short bowel syndrome(OTH). Complications such as bloodstream infections(CRBSI) and hospitalizations(HOSP) are seen in these patients. We wanted to determine the incidence of HPN associated complications in patients with MOT and SBS. Methods: Medical records of chronic HPN patients from one home care provider from 5/2005-7/2007 were recorded to determine the incidence of CRBSI, HOSP and days in HOSP(HOSPD). The patients were divided into two groups based on their underlying disease(MOT or OTH). Comparisons were made to determine if either group had a greater incidence of CRBSI, HOSP or HOSPD. Data are reported as n(% f) for gender or mean±standard deviation/1,000 catheter days. Statistical analysis was performed using a T test, Chi Square and logistic regression. Minitab V.14 was

Diffuse Noxious Inhibitory Controls (DNIC) Are Compromised in Patients with Irritable Bowel Syndrome Compared to Healthy Controls Steve Heymen, William Maixner, William E. Whitehead, Rebecca R. Klatzkin, Beth Mechlin, Kathleen C. Light Introduction: Visceral hyperalgesia is observed in most patients with Irritable Bowel Syndrome (IBS). Recent investigations showing somatic hyperalgesia, not seen in earlier IBS studies, suggest the possibility of a dysfunction in central pain regulatory mechanisms. Dysregulation of the endogenous pain regulatory mechanism known as DNIC has been consistently demonstrated in two other chronic pain conditions, Fibromyalgia and Temporomandibular Disorder, which show high comorbidity with IBS. In DNIC, descending serotonergic and opioidergic pain inhibitory signals are initiated by one pain stimulus that then

AGA Abstracts

A-562