Impaired gastrocolonic response and peristaltic reflex  in slow-transit constipation: role of 5-HT3 pathways

Colonic motility is modulated by the 5-hydroxytryptamine (5-HT)3-dependent gastrocolonic response and 5-HT3-independent peristaltic reflex. We compared descending colon tone responses to antral distension, duodenal lipid perfusion, and colonic distension after double-blind placebo or granisetron in 13 healthy volunteers and nine slow-transit constipated patients. Antral distension (100–300 ml) and duodenal lipids (3 kcal/min) evoked increases in colon tone in volunteers, which were blunted in constipated patients ( P < 0.05). Granisetron (10 μg/kg) reduced responses to antral distension and lipids in volunteers and to lipids in constipated patients ( P < 0.05). The ascending contraction of the peristaltic reflex was blunted in constipated patients ( P < 0.05), whereas descending responses were similar. Granisetron did not modify the peristaltic reflex. Colonic responses to bethanechol were similar in patients and volunteers. In conclusion, antral distension- and duodenal lipid-activated gastrocolonic responses and ascending contractions of the peristaltic reflex are impaired with slow-transit constipation with loss of both 5-HT3-dependent and -independent function. Thus abnormalities of neural reflex modulation of colonic motor function may play pathophysiological roles in slow-transit constipation.

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Differential 5-HT3 mediation of human gastrocolonic response and colonic peristaltic reflex

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.275.3.g498 ◽

1998 ◽

Vol 275 (3) ◽

pp. G498-G505 ◽

Cited By ~ 9

Author(s):

Einar S. Björnsson ◽

William D. Chey ◽

Uri Ladabaum ◽

Michelle L. Woods ◽

Forrest G. Hooper ◽

...

Keyword(s):

Motor Function ◽

Healthy Human ◽

Double Blind ◽

Peristaltic Reflex ◽

Colonic Motor ◽

Human Volunteers ◽

Gastrocolonic Response ◽

Colonic Distension ◽

Antral Distension

Colonic motor function is modulated by extended and local neural reflexes involving unknown mediators. To test the role of serotonin (5-HT3) pathways, increases in colonic tone during antral distension and duodenal lipid perfusion (gastrocolonic responses) and changes in orad and caudad colonic tone in response to local colonic distension (peristaltic reflex) were measured after double-blind granisetron (10 μg/kg) or placebo infusion in healthy human volunteers. Antral distension evoked increases in colonic tone, which were blunted by granisetron ( P < 0.05) without effects on antral compliance. Intraduodenal lipid perfusion also evoked increased colonic tone, which was reduced by granisetron ( P < 0.05). In contrast, orad colonic contractions and caudad relaxations and contractions during colonic distension were unaffected by granisetron. In conclusion, 5-HT3 receptor antagonism blunts both the mechano- and chemoreceptor components of the human gastrocolonic response without altering antral compliance. In contrast, 5-HT3 pathways play no role in the ascending or descending components of the colonic peristaltic reflex. These findings demonstrate different roles for 5-HT3 receptors in the control of colonic motor function by the proximal gastrointestinal tract and by local neural reflexes.

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273 Efficacy of Sacral Nerve Stimulation for Treating Slow Transit Constipation: A Randomised, Double-Blind, Placebo-Controlled, 2 Phase Crossover Study

Gastroenterology ◽

10.1016/s0016-5085(13)60219-x ◽

2013 ◽

Vol 144 (5) ◽

pp. S-61 ◽

Cited By ~ 1

Author(s):

Philip G. Dinning ◽

Linda M. Hunt ◽

Vicki E. Patton ◽

Val Gebski ◽

Michael P. Jones ◽

...

Keyword(s):

Crossover Study ◽

Nerve Stimulation ◽

Sacral Nerve Stimulation ◽

Slow Transit Constipation ◽

Double Blind ◽

Double Blind Placebo ◽

Sacral Nerve ◽

Slow Transit ◽

Transit Constipation

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Colonic electrical stimulation promotes colonic motility through regeneration of myenteric plexus neurons in slow transit constipation beagles

Bioscience Reports ◽

10.1042/bsr20182405 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 2

Author(s):

Yongbin Wang ◽

Qian Wang ◽

Kudelaidi Kuerban ◽

Mengxue Dong ◽

Feilong Qi ◽

...

Keyword(s):

Electron Microscopy ◽

Electrical Stimulation ◽

Western Blot ◽

Myenteric Plexus ◽

Pulse Train ◽

Colonic Motility ◽

Slow Transit Constipation ◽

Slow Transit ◽

Transit Constipation ◽

Colonic Electrical Stimulation

Abstract Slow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well established that STC is mostly caused by disorders of relevant nerves, especially the enteric nervous system (ENS). Colonic electrical stimulation (CES) has been regarded as a valuable alternative for the treatment of STC. However, little report focuses on the underlying nervous mechanism to normalize the delayed colonic emptying and relieve symptoms. In the present study, the therapeutic effect and the influence on ENS triggered by CES were investigated in STC beagles. The STC beagle model was established by oral administration of diphenoxylate/atropine and alosetron. Histopathology, electron microscopy, immunohistochemistry, Western blot analysis and immunofluorescence were used to evaluate the influence of pulse train CES on myenteric plexus neurons. After 5 weeks of treatment, CES could enhance the colonic electromyogram (EMG) signal to promote colonic motility, thereby improving the colonic content emptying of STC beagles. HE staining and transmission electron microscopy confirmed that CES could regenerate ganglia and synaptic vesicles in the myenteric plexus. Immunohistochemical staining showed that synaptophysin (SYP), protein gene product 9.5 (PGP9.5), cathepsin D (CAD) and S-100B in the colonic intramuscular layer were up-regulated by CES. Western blot analysis and immunofluorescence further proved that CES induced the protein expression of SYP and PGP9.5. Taken together, pulse train CES could induce the regeneration of myenteric plexus neurons, thereby promoting the colonic motility in STC beagles.

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