Enteric nervous system: sensory physiology, diarrhea and constipation.

Area of Science:

• Gastroenterology
• Neuroscience
• Pharmacology

Background:

• The enteric nervous system (ENS) governs gastrointestinal secretion and motility, maintaining homeostasis.
• Disorders of the ENS, including diarrhea and constipation, significantly impact gut function.
• Mechanosensory detection plays a key role in ENS integration and behavior.

Purpose of the Study:

• To summarize advancements in understanding mechanosensory detection within the ENS.
• To review the role of disordered ENS integration in diarrhea and constipation.
• To discuss current and future pharmacotherapeutic strategies for ENS disorders.

Main Methods:

• Review of current scientific literature on ENS mechanoreception and function.
• Analysis of neuronal discharge patterns in response to mechanical stimuli.
• Evaluation of pharmacologic agents targeting mucosal chloride channels.

Main Results:

• A majority of ENS neurons exhibit discharge in response to physical distortion.
• Pharmacologic agents that open chloride channels in the mucosal epithelium represent viable therapeutic options for constipation.
• Lubiprostone, an FDA-approved drug, enhances luminal content liquidity by activating chloride channels.

Conclusions:

• Mechanoreception is essential for negative feedback control within the ENS.
• Identifying specific mechanosensory neurons is critical for understanding neurogenic secretory diarrhea and constipation.
• Targeting chloride channels, such as with lubiprostone, offers a promising strategy for chronic constipation, though its precise mechanism of action is under investigation.