Enteric nerves within the intermuscular plexus (Auerbach’s plexus) mainly control colorectal motility, and those within the submucosal plexus (Meissner’s plexus) mainly control mucosal secretion and blood flow. Neurotransmitters found in the ENS can either stimulate (acetylcholine, serotonin, histamine, cholecystokinin, angiotensin, motilin, and gastrin) or inhibit (dopamine, noradrenalin, glucagon, vasoactive intestinal polypeptide, enkephalin, and somatostatin) motility. Receptors for histamine and serotonin have been classified into subgroups. Agonists and antagonists have been developed and may have a clinical role in the future.

The ENS generally consists of three types of neurons:

Sensory neurons, specialized to detect mechanical stimuli, temperature, or chemical properties, interact through multiple interneurons with motor neurons to either stimulate or inhibit smooth muscle contraction. Interneurons also integrate stimuli from the ENS with the extrinsic nerve system and hormones. Reflexes within the ENS can thus be activated by both local and extrinsic stimuli. Thus efferent parasympathetic fibers within the vagal and splanchnic nerves can stimulate motility over large distances of the gastrointestinal tract.

Sympathetic nerve fibers and prevertebral sympathetic ganglia are considered the most important mediators of the gastrocolic response, which mediates colorectal phasic and tonic activity after a meal. Parasympathetic activity within the ENS depolarizes colorectal smooth muscle cells through the release of acetylcholine and stimulates colorectal motility. If parasympathetic innervation is lost, colorectal reflex activity is reduced. A clinically important example is severe defecation disorders caused by reduced left colonic and rectal reflex activity and tone after damage to the splanchnic nerves or spinal cord lesions of the conus medullaris or cauda equina.

The colon and rectum are insensitive to most stimuli; however, they are very sensitive to stretching. The subjective experience of rectal sensation is a feeling of rectal fullness and an urge to defecate. By contrast, colonic distension produces pain and colic. The location of rectal stretch receptors is controversial. The rectal mucosa contains no specific receptor type, which probably explains the poor discriminatory quality of rectal sensation.

Higher brain centers that influence colonic motility include the frontal regions of the cerebral cortex, the stria terminalis, the amygdala, and the hypothalamus. The effects on colorectal motility are mainly inhibitory; thus a loss of supraspinal control of the sacral reflex center may cause increased left colonic and rectal reflex activity and tone (Fig. 3.2).

Thyroid hormone stimulates colorectal motility and epinephrine reduces it. The unique ability of the immune system to recognize specific antigens makes immunoneuronal integration important for bowel function. Once the immune system within the bowel wall becomes sensitized to specific antigens, a second exposure to that antigen causes mast cells to release histamine and other messengers. Histamine acts on intestinal H₂ receptors, stimulating electrolyte, water, and mucus secretion, and promotes strong contractions, called “power propulsion,” spanning large distances within the bowel. Consequently, potentially harmful antigens are quickly cleared from the lumen.