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Colitis-induced neuroplasticity disrupts motility in the inflamed and post-inflamed colon
Gary M. Mawe
Gary M. Mawe
Published March 2, 2015
Citation Information: J Clin Invest. 2015;125(3):949-955. https://doi.org/10.1172/JCI76306.
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Review Series

Colitis-induced neuroplasticity disrupts motility in the inflamed and post-inflamed colon

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Abstract

Effective colonic motility involves an intricate pattern of excitatory and inhibitory neuromuscular signals that arise from the enteric neural circuitry of the colon. Recent investigations have demonstrated that inflammation leads to a variety of changes in the physiological properties of the neurons in this circuitry, including hyperexcitability of neurons at the afferent end of the peristaltic reflex, synaptic facilitation, and attenuated inhibitory neuromuscular transmission. Furthermore, links have been established between these changes and disrupted motor activity in the colon, and we now know that some of these changes persist long after recovery from inflammation. It is highly likely that inflammation-induced neuroplasticity, which is not detectable by clinical diagnostics, contributes to disrupted motility in active and quiescent inflammatory bowel disease and in functional gastrointestinal disorders.

Authors

Gary M. Mawe

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Figure 1

The basic elements of the peristaltic reflex circuit in the colon and changes detected at specific sites of this circuitry in colitis.

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The basic elements of the peristaltic reflex circuit in the colon and ch...
(i) A stimulus in the lumen, such as stretch or distension, results in the release of serotonin by the epithelial cells in the gut mucosa. (ii) The serotonin and mechanical stretch activate afferent neurons. These neurons, in turn, activate sensory afferent fibers that send projections into the submucosal and myenteric plexuses. This in turn activates two limbs of the peristaltic reflex. (iii) Upstream of the stimulus, interneurons synapse with and activate excitatory motor neurons that release acetylcholine and tachykinins to trigger smooth muscle contractions. (iv) Downstream of the stimulus, interneurons synapse with and activate inhibitory motor neurons that release NO and purines to trigger smooth muscle relaxation. The combination of upstream contraction and downstream relaxation creates a pressure gradient that drives the luminal contents from the proximal to the distal end of the gut. Colitis is characterized by increased serotonin availability, increased excitability of afferent neurons, facilitation of interneuronal synaptic activity, decreased purinergic neuromuscular transmission, and loss of myenteric neurons, which together lead to a mixture of overlapping excitatory and inhibitory motor outputs in the inflamed region (see Figure 2). EEC, enteroendocrine cell.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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