Differential symptomatic and electrogastrographic effects  of distal and proximal human gastric distension

Nausea and gastric dysrhythmias occur in conditions associated with gastric distension. The roles of distal and proximal gastric mechanoreceptors in these responses are unexplored. Because antral distension induces vomiting in animals and antral and fundic vagal afferent discharges differ, we hypothesized that distal gastric distension in humans leads to greater symptomatic and dysrhythmic responses than proximal distension. Symptoms and electrogastrograms were recorded in healthy humans during distal and proximal gastric distension with a barostat. Distal but not proximal distension induced nausea and a 747 ± 250% increase in dysrhythmic power ( P < 0.05), responses not affected by granisetron, indomethacin, or atropine, agents that block dysrhythmias in other settings. In the distal stomach, bloating and pain developed at lower pressures ( P < 0.05) not modified by granisetron, and compliance was significantly lower ( P < 0.05). In conclusion, gastric mechanoreceptor activation in the less-compliant distal stomach produces nausea and dysrhythmias via non-5-hydroxytryptamine3(5-HT3), non-prostaglandin-dependent, and noncholinergic pathways. Distal mechanoreceptor activation induces greater bloating and pain than proximal mechanoreceptor activation via 5-HT3-independent pathways.

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CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00809.2004 ◽

2005 ◽

Vol 289 (3) ◽

pp. R695-R703 ◽

Cited By ~ 39

Author(s):

E. H. E. M. van de Wall ◽

P. Duffy ◽

R. C. Ritter

Keyword(s):

Vagal Afferents ◽

Gastric Distension ◽

Solitary Tract ◽

C Fibers ◽

Balloon Distension ◽

Electrophysiological Responses ◽

Vagal Afferent ◽

Fos Expression ◽

Afferent Response ◽

And Control

Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.

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GABAB receptors on vagal afferent pathways: peripheral and central inhibition

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.4.g658 ◽

2001 ◽

Vol 280 (4) ◽

pp. G658-G668 ◽

Cited By ~ 36

Author(s):

Elita R. Partosoedarso ◽

Richard L. Young ◽

L. Ashley Blackshaw

Keyword(s):

Brain Stem ◽

Gabab Receptors ◽

Vagal Afferents ◽

Gastric Distension ◽

Neuronal Responses ◽

Afferent Pathways ◽

Central Inhibition ◽

Vagal Afferent ◽

Vagal Efferents ◽

Cgp 35348

To investigate GABAB receptors along vagal afferent pathways, we recorded from vagal afferents, medullary neurons, and vagal efferents in ferrets. Baclofen (7–14 μmol/kg iv) reduced gastric tension receptor and nucleus tractus solitarii neuronal responses to gastric distension but not gastroduodenal mucosal receptor responses to cholecystokinin (CCK). GABAB antagonists CGP-35348 or CGP-62349 reversed effects of baclofen. Vagal efferents showed excitatory and inhibitory responses to distension and CCK. Baclofen (3 nmol icv or 7–14 μmol/kg iv) reduced both distension response types but reduced only inhibitory responses to CCK. CGP-35348 (100 nmol icv or 100 μmol/kg iv) reversed baclofen's effect on distension responses, but inhibitory responses to CCK remained attenuated. They were, however, reversed by CGP-62349 (0.4 nmol icv). In conclusion, GABAB receptors inhibit mechanosensitivity, not chemosensitivity, of vagal afferents peripherally. Mechanosensory input to brain stem neurons is also reduced centrally by GABAB receptors, but excitatory chemosensory input is unaffected. Inhibitory mechano- and chemosensory inputs to brain stem neurons (via inhibitory interneurons) are both reduced, but the pathway taken by chemosensory input involves GABAB receptors that are insensitive to CGP-35348.

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H. pylori and transient lower esophageal sphincter relaxations induced by gastric distension in healthy humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.2.g350 ◽

2001 ◽

Vol 281 (2) ◽

pp. G350-G356 ◽

Cited By ~ 17

Author(s):

Frank Zerbib ◽

Valérie Bicheler ◽

Véronique Leray ◽

Madeleine Joubert ◽

Stanislas Bruley des Varannes ◽

...

Keyword(s):

Helicobacter Pylori ◽

Lower Esophageal Sphincter ◽

Proinflammatory Cytokine ◽

Healthy Subjects ◽

Gastric Distension ◽

Healthy Humans ◽

Biopsy Specimens ◽

Esophageal Sphincter ◽

H Pylori

The role of Helicobacter pylori infection in the control of lower esophageal sphincter (LES) motility, especially the occurrence of transient LES relaxations (TLESRs), was studied in eight H. pylori-positive and eight H. pylori-negative healthy subjects. During endoscopy, biopsy specimens were taken from the cardia, fundus, and antrum for determinations of H. pyloristatus, gastritis, and proinflammatory cytokine mucosal concentrations. LES motility was monitored during three different 30-min periods: baseline, gastric distension (barostat), and gastric distension with CCK infusion. Gastric distension significantly increased the TLESR rate, whereas CCK increased the rate of distension-induced TLESRs further and reduced resting LES pressure without significant differences between infected and noninfected subjects. H. pylori status did not influence resting LES pressure or gastric compliance. Cytokine mucosal concentrations were increased in infected patients, but no correlation was found with the TLESR rate, which was also independent of inflammation at the cardia, fundus, and antrum. These results suggest that H. pylori-associated inflammation does not affect the motor events involved in the pathogenesis of gastroesophageal reflux.

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Inhibition of gastric mechanoreceptor discharge by cholecystokinin in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.268.2.g355 ◽

1995 ◽

Vol 268 (2) ◽

pp. G355-G360 ◽

Cited By ~ 8

Author(s):

D. Grundy ◽

V. Bagaev ◽

K. Hillsley

Keyword(s):

Indirect Effects ◽

Time Course ◽

Positive Response ◽

Pressure Response ◽

Gastric Distension ◽

Afferent Fibers ◽

Before And After ◽

Afferent Discharge ◽

Vagal Afferent

The aim of the present study was to investigate electrophysiologically the effect of systemic cholecystokinin (CCK) on the discharge of vagal gastric mechanoreceptors. Twenty-two single vagal afferent fibers were selected for the investigation of responses to intravenous CCK octapeptide (CCK-8) on the basis of a positive response to gastric distension. Resting discharge in these afferent fibers was 1.3 +/- 0.3 impulses.s-1 and increased to 9.2 +/- 0.9 impulses.s-1 during distension (P < 0.0001), CCK (20-100 pmol iv) caused a gastric relaxation of 2.1 +/- 0.2 cmH2O and inhibition of phasic motility. The discharge of 20/22 of vagal tension receptors closely followed the magnitude and time course of the fall in pressure. Mean discharge before and after CCK (50 pmol) was 7 +/- 0.9 and 3.9 +/- 0.8 impulses.s-1, respectively (P < 0.001, n = 22). Both the pressure response and the concomitant changes in afferent discharge were abolished by L-364,718 (1.2 mg/kg iv). Only two afferent units failed to show a decrease in firing following CCK (50 pmol), and at 500 pmol the discharge of these units was augmented. In conclusion, CCK (50 pmol) has predominantly indirect effects on gastric mechanoreceptors, which decrease their firing in association with gastric relaxation.

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Effect of the kappa agonist fedotozine on perception of gastric distension in healthy humans

Alimentary Pharmacology & Therapeutics ◽

10.1046/j.1365-2036.1996.109280000.x ◽

1996 ◽

Vol 10 (6) ◽

pp. 919-925 ◽

Cited By ~ 54

Author(s):

B. COFFIN ◽

D. BOUHASSIRA ◽

R. CHOLLET ◽

B. FRAITAG ◽

C. DE MEYNARD ◽

...

Keyword(s):

Gastric Distension ◽

Healthy Humans ◽

Kappa Agonist

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Effects of capsaicin on the perception of gastric distension and fundic tone in healthy humans

Gastroenterology ◽

10.1016/s0016-5085(03)81271-4 ◽

2003 ◽

Vol 124 (4) ◽

pp. A254

Author(s):

Kwang-Jae Lee ◽

Rita Vos ◽

Jozef Janssens ◽

Jan Tack

Keyword(s):

Gastric Distension ◽

Healthy Humans

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GABA, receptors inhibit vagal afferent mechanoreceptor responses to gastric distension

Gastroenterology ◽

10.1016/s0016-5085(01)80027-5 ◽

2001 ◽

Vol 120 (5) ◽

pp. A5-A6

Author(s):

S SMID ◽

L BLACKSHAW

Keyword(s):

Gaba Receptors ◽

Gastric Distension ◽

Vagal Afferent

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Mechanosensitive Properties of Gastric Vagal Afferent Fibers in the Rat

Journal of Neurophysiology ◽

10.1152/jn.1999.82.5.2210 ◽

1999 ◽

Vol 82 (5) ◽

pp. 2210-2220 ◽

Cited By ~ 72

Author(s):

Noriyuki Ozaki ◽

J. N. Sengupta ◽

G. F. Gebhart

Keyword(s):

Acute Inflammation ◽

Platelet Activating Factor ◽

Response Threshold ◽

Gastric Distension ◽

Intragastric Pressure ◽

Afferent Fibers ◽

Slow Adaptation ◽

Resting Activity ◽

Response Thresholds ◽

Vagal Afferent

Single, teased fiber recordings were made from the decentralized right cervical vagus nerve (hyponodal) of the rat. A total of 67 afferent fibers that responded to gastric distension (GD) were studied: 9 fibers were stimulated by phasic balloon GD, 58 by more natural fluid GD. All balloon GD–responsive fibers had resting activity (3.1 imp/s), and 57/58 fluid GD responsive fibers had resting activity (1.3 imp/s). All balloon GD–responsive fibers exhibited a dynamic response to phasic distension followed by slow adaptation, whereas fluid GD–responsive fibers exhibited increasing responses as intragastric pressure increased, followed typically by slow adaptation. Responses to graded GD were studied in all fibers, and all gave increasing responses to increasing pressures (5–60 mmHg). Thresholds for response varied between 0 and 18 mmHg. Mean response thresholds for two durations of fluid GD (30 and 60 s) were 5.6 and 3.9 mmHg; the mean response threshold to phasic balloon GD (30 s duration) was 5.3 mmHg. The potential sensitizing effect of platelet activating factor (PAF, 50 or 100 ng · kg−1 · min−1 for 20 min) infused into the gastric artery was studied in 20 fibers. Fifteen fibers exhibited an increase in spontaneous activity; intragastric pressure also slightly increased during PAF infusion. The increase in activity produced by PAF was attenuated in the presence of the PAF receptor antagonist WEB 2086. After PAF-induced acute inflammation of the stomach, three of five fibers studied did not exhibit any change in response to graded GD. The present study characterized distension-sensitive afferent fibers in the right cervical vagus innervating the stomach of the rat by balloon GD and fluid GD. The results document that all distension-sensitive gastric vagal afferent fibers encoded the intensity of GD, but none had response thresholds in what might be considered the noxious range. PAF infusion activated mechanosensitive gastric vagal afferent fibers, but acute inflammation produced by PAF did not sensitize responses to GD.

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Peripheral bombesin induces gastric vagal afferent activation in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.271.6.r1584 ◽

1996 ◽

Vol 271 (6) ◽

pp. R1584-R1593 ◽

Cited By ~ 6

Author(s):

E. Yoshida-Yoneda ◽

T. J. O-Lee ◽

J. Y. Wei ◽

S. R. Vigna ◽

Y. Tache

Keyword(s):

Specific Binding ◽

Receptor Activation ◽

Gastric Distension ◽

Specific Receptor ◽

Afferent Activation ◽

Gastric Smooth Muscle ◽

Afferent Discharge ◽

Vagal Afferent ◽

Bombesin Antagonist ◽

Stimulation Of

Bombesin's influence on gastric vagal afferent discharge (GVAD) was studied in urethan-anesthetized rats. Vehicle and peptides were injected intravenously at 30-min intervals. Cholecystokinin (CCK; 300 pmol) and bombesin (300 pmol) increased ongoing multiunit GVAD by 153 +/- 59 and 162 +/- 37%, respectively; similar increases were induced by a second injection of bombesin and CCK. The bombesin antagonist, ICI-216140, prevented bombesin-induced increase in GVAD, whereas the CCK response was not influenced. The CCK-A receptor antagonist devazepide reduced the activation of GVAD induced by bombesin from 107 +/- 11 to 63 +/- 6%, while abolishing the CCK response. Devazepide given alone or in combination with ICI-216140 did not modify gastric distension (3 ml)-induced increase in GVAD. Of 22 single units that were activated by gastric load (4 ml), 17 and 20 units responded also to bombesin (620 pmol) and CCK (870 pmol), respectively. Of the nine units that did not respond to gastric load, eight had an increase in GVAD induced by both bombesin and CCK. There was no specific binding of 125I-labeled [Tyr4]bombesin on cervical vagus, either intact or 24 h after ligation. These data suggest that intravenous bombesin-induced stimulation of GVAD is indirect and initially mediated through specific receptor activation influencing gastric smooth muscle and the release of CCK.

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