A840 AGA ABSTRACTS

4413INTRACOLONIC GLYCEROL INDUCES ABDOMINAL CON·TRACTIONS IN RATS: ROLE OF PREGEBALIN AND MOR·PHINE.Helene Eutamene, Magali Toulouse, Vassilia Theodorou, Maria Chovet,Anneth Doherty, Jean Fioramonti, Lionel Bueno. INRAIIRJ Parke Davis,Toulouse, France; Esap, Toulouse, France; IRJ Parke Davis, Fresnes,France; INRA, Toulouse, France.

Recent studies have shown that pregabalin (CI 1(08), a gabapentin analogpossesses antihyperalgesic activity in animal models of hyperalgesia in­duced by stress- and LPS in response to rectal distension. In rats, intraco­Ionic infusion of a chemical irritant: glycerol, is able to trigger nociceptiveinputs as evidenced by the occurence of spontaneous abdominal contrac­tions. This work was designed to evaluate the influence of pregabalin andmorphine on this abdominal response. Methods: Nine groups of 8 maleWistar rats (200-250 g) were used. Animals were premedicated withacepromazine and ketamine for surgery. After laparotomy, a siliconecatheter (internal diameter: 0.5 mm) was inserted into the proximal colonat 5 em from the caeco-colonic junction. Three pairs of electrodes wereimplanted in striated muscles of the abdomen in order to record spike burts(EMG) as an index of abdominal cramps. After surgical recovery (5 days),glycerol diluted in water (60/40 % v/v) or saline were infused intracoloni­cally at a rate of 0.75 ml/h during 20 min (2 groups). EMG recordingstarted 30 min before intracolonic infusion. Using the same protocol,pregabalin (3,10 and 30 mg/kg po) or morphine (3 mg/kg sc) or theirvehicle were administered prior to the infusion of glycerol (7 groups).Results: Intracolonic infusion of glycerol significantly enhanced the num­ber of abdominal spike burst (290%) compared with abdominnal contrac­tions recording before infusion. This effect appeared 20 min after startingglycerol infusion, and a progressive recovery of a normal frequency ofburst was observed 40 min after the beginning of infusion Pregabalin (3, 10and 30 mg/kg po) dose-dependently inhibited the glycerol-induced abdom­inal cramps (27, 56 and 70 % respectively). Morphine (3 mg/kg sc) alsoinhibited this effect (49%). Conclusion: These results indicate that intra­colonic glycerol is able to produce morphine-sensible abdominal cramps.Oral pregabalin exhibits antinociceptive effect by suppressing these glyc­erol-induced abdominal contractions.

GASTROENTEROLOGY Vol. 118, No.4

4415LONG TERM EFFECTS OF AN ACUTE CHEMICALLY INDUCEDCOLITIS ON THE VISCEROMOTOR RESPONSE TO MECHAN·ICAL COLORECTAL DISTENSION.Juergen Gschossmann, Gerald Holtmann, Tobias Liebregts, Birgit Adam,Sandra Denecke, Vesna Zegarac, Joerg Zeeh, Peter Hoffmann, GuidoGerken, Univ of Essen, Dept of Gastroenterology & Hepatology, Essen,Germany.

Background: Postinflammatory alterations of visceral sensory functionmay playa role in the pathophysiology of functional GI disorders. Thisstudy aimes to characterize postinflammatory changes of mechanosensoryfunction in an animal model. Methods: We performed colorectal disten­sions with a barostat device in fasted, conscious male Lewis rats(n=42).After the baseline measurement,acute colitis was induced by instillation oftrinitrobenzenesulphonic acid (TNB). The visceromotor response to tonicdistension (60 mmHg/3 min) was assessed by measuring electromyo­graphic (EMG)activity of abdominal wall musculature before and 2,4 and15 weeks after TNB instillation. In addition, tissue samples from pairedcontrols were obtained to assess histologic tissue alterations. Results: TNBbut not saline induced an acute colitis with a maximum of the histologicalalterations occurring 5 days after instillation. Colitis rapidly heals and therewas no histologic evidence for colitis after 14 days. In control experiments(colonic saline instillation) repeated colorectal distension resulted in asignificant decrease of the response to distension by 42::': 17% (p<0.05)after 2 weeks, 51::':18% after 4 weeks and 51::':22% after 15 weekscompared to baseline values. In contrast, animals after TNB-colitis had an54::': 17% higher overall response (p<0.05) and did not respond with adecrease of the motor response after repeated distension (p>0.5 vs. con­trols). The increased EMG responses to standardized colorectal distensionremained significant 2,4 and 15 weeks after induction of the colitis.Conclusion: Even after complete healing of lesions, a TNB-colitis has longlasting effects on the visceromotor response to colorectal distension. Theobserved effects may represent an animal model for the pathomechanismsinvolved in the pathogenesis of patients with postinfectious IBS.

Tab.: Abdominal EMG (ltV) inresponse tostandardized colorectal distension

4416SECRETIN INHIBITS VAGAL AFFERENT NERVE DISCHARGEIN RESPONSE TO GASTRIC DISTENSION IN RATS.Je Lu, Zong-Seng Huang, James P. Li, Ying Zhao, William Y. Chey,Chongqing Univ of Med Sci, Chongqing, P. R. China; Univ of RochesterMed Ctr, Rochester, NY; Chongqing Teaching Coil, Chongqing, P. R.China.

We have previously shown that secretin regulates pancreatic exocrinesecretion and gastric acid secretion via a vagal afferent pathway (Am. J.Physiol. 269:0305,1995 and 275:022,1998). However, there is few directevidence on the electrophysiologic characteristics of vagal afferent nerve inresponse to secretin. In the present study, we investigated the action ofsecretin on vagal afferent nerve discharge by recording sensory impulsesfrom SUbdiaphragmatic vagal afferent nerve fibers in response to gastricdistension (GD) with or without secretin and duodenal acidification inanesthetized rats. Methods: In Wistar rats with jugular vein catheters, a 20em upper small intestinal loop was made for infusion of acid or saline. Thesubdiaphragmatic vagal trunk was insolated and thin filaments of afferentfibers were teased from the intact vagal trunk and placed on a bipolarrecording electrode. The sensory impulses were recorded using a windowdiscriminator before and after GD with a gastric balloon containing 2 ml ofwater. Secretin (2.5, 5, 10 pmollkg iv) or 0.03 N HCl (9 ml/h id) wasadministered after GD, respectively. In seven rats treated with acid (id), arabbit antisecretin serum or normal rabbit serum (NRS) was injected (iv) in0.1 mllrat 30 min before duodenal infusion of acid. Results: GD signifi­cantly increased vagal afferent impulses compared with that in rest period(p<O.OI). Secretin given iv at 2.5-10 pmol/kg dose-dependently inhibitedthe sensory impulses in response to GD. Duodenal acidification with 0.03N HCl also significantly suppressed GD-induced vagal sensory impulse(p<0.05), which started 20 min after HCl infusion, lasting more than 40min. Antisecretin serum, but not NRS, abolished HCI-induced inhibition ofvagal sensory impulse. Conclusion: these observations provided directelectrophysiological evidences that both exogenous and endogenous secre­tin play an important physiological role in suppression of discharge fromvagal sensory afferent nerve in response to GD in rats.

4414ENHANCEMENT OF VISCERAL PAIN INDUCED BY COLONICDISTENSION IN COW'S MILK SENSITIZED GUINEA PIGS.Helene Eutamene, Vassilia Theodorou, Jean Fioramonti, Lionel Bueno,INRA, Toulouse, France; InralEsap, Toulouse, France.

Mast cells playa pivotal role in food antigen sensitization and subsequentanaphylactic reactions. Mast cell degranulation releases proalgesic medi­ators and induces a nociceptive hypersensitivity to rectal distension in rats.Our study was aimed to evaluate the visceral nociceptive response beforeand after antigenic challenge in guinea pigs sensitized to cow's milk.Methods: One group of 10 Dunkin-Hartley guinea pigs (250-300g) wassensitized to cow's milk by giving fresh pasteurized cow's milk to drink for4 weeks. One other group had water available instead of milk and was usedas control. One week after this delay, blood was drawn to determinespecific IgE and IgG titers by passive cutaneous anaphylaxis (PCA) test.Then the animals were equipped with an intracolonic catheter and elec­trodes in muscles of the abdomen to record abdominal spike bursts as anindex of nociception. Under pentobarbital anaesthesia, a barostatic colo­rectal distension (CRD) was performed with a balloon (3 em) inflated by 5min steps of 20 mmHg, from 0 to 60 mmHg. After the first CRD session,antigenic challenge was performed by intracolonic infusion of b-Iactoglob­ulin (100 mg) and 30 min later a new CRD session was performed. Results:In response to CRD, abdominal cramps observed in sensitized (beforechallenge) guinea pigs were significantly enhanced by 243; 115 and 122%for each volume of distension 20, 40 and 60 mmHg respectively comparedto control animals. Antigenic challenge also significantly enhanced abdom­inal contractions by 334; 243; and 260% respectively compared to naiveanimals, and by 92; 78; 81% respectively compared to sensitized guineapigs. Conclusion: In guinea pigs, sensitization to cow's milk is associatedwith visceral hypersensitivity to that is accentuated after antigenic chal­lenge. These data support that food allergy may playa role in the genesisof gut hypersensitivity to distension associated with functional boweldisorders.

TNBcoiltiscontrols

baseline

812±80830 +92

week 2

1051 ±150480±80

week 4

1313 ±200403± 75

week 15

1368 ±287407 +100