Chapter 11 - Responses of afferent neurons to the contents of the digestive tract, and their relation to endocrine and immune responses
Introduction
The lining of the gastrointestinal tract is our largest external surface. This surface performs a difficult task: it needs to be in immediate contact with the contents of the intestine so that nutrients are efficiently absorbed, and it needs to protect against the intrusion of harmful entities, such as toxins and bacteria that may enter the digestive system with food. Thus the state of the gut needs to be monitored, and the gut itself needs to react to its contents. Signalling is through the immune system, endocrine hormones and the nervous system (Fig. 1). It is therefore no surprise that the digestive tract has three control systems that are more extensive than those of any other organ: the gut immune system, in which 70% of the body's immune cells are found (Heel et al., 1997); the gastroenter-opancreatic endocrine system, which uses more than 30 identified hormones (Brand and Schmidt, 1995); and the enteric nervous system, which contains of the order of 108 neurons (Furness and Bornstein, 1995).
Thus, the gastrointestinal tract has an integrated response to changes in its lumenal contents. When this response is maladjusted, or is overwhelmed by injurious substances, the consequences can be severe, as in cholera intoxication, or debilitating, as in the irritable bowel syndrome. Thus it is essential to obtain a full understanding of the manner in which the lumenal content of the gut is sensed, and how the body reacts to the information.
This review deals principally with the neurons of the gut, but also includes descriptions of the other major gut signalling systems, the gut immune and gut endocrine systems.
Section snippets
The gut immune system
The vast surface area presented by the lining of the gastrointestinal tract must defend the body against many potentially injurious substances in the food that accompanies food or drink, or is produced by degradation from food. At the same time, it must welcome and absorb nutrients into the body. To defend the otherwise highly permeable epithelial membrane, the small and large intestines have developed a number of specialisations, collectively called gut associated lymphoid tissue (GALT).
The gut endocrine system
The endocrine cells of the gastrointestinal tract are dispersed amongst the epithelial cells of its lumenal surface, and react to changes in the gut contents by releasing hormones that are, in general, targeted to other parts of the digestive system. For example, cholecystokinin (CCK) is released from the duodenum in response to a meal, the major chemicals signalling this release being the products of the breakdown of fats and proteins. The major actions of CCK are on the pancreas to release
The gut nervous system
Monitoring and control of the digestive system through the nervous system is hierarchical. The gut contains an extensive collection of neurons, the enteric nervous system, within its walls (Furness and Bornstein, 1995). This intrinsic nervous system is capable of generating appropriate reflex responses to the contents of its lumen; for example, intrinsic reflexes generate mixing movements of the muscle, cause local changes in blood flow, and modulate secretion of water and electrolytes. The
The interactions between afferent neurons, immune and endocrine systems
The lamina propria is a milieu in which the secreted products of inflammatory cells, endocrine hormones and afferent nerve endings interact with receptors on nerve endings and cells of each of the other two systems (Fig. 4). Amongst the events that occur are the activation or sensitisation of afferent nerve endings by inflammatory mediators, the actions of neurotransmitters released by axon reflexes on other axons, immune cells, arteriole diameter, vascular permeability and on the epithelium
Conclusions
It is well established that neurons, endocrine hormones and the immune system all react to changes occurring in the gut. Although many of the effects mediated through these systems have been elegantly dissected, the subtleties of their interactions are still being unravelled. In pathological conditions, such as inflammation, it has been easy to reveal the participation of many factors released from the inflamed tissue, including substances from neurons, immune cells and endocrine cells, but it
Acknowledgements
This work was supported by a grant from the National Health & Medical Research Council of Australia (grant no. 963213). We thank Soibhan Lavin for excellent assistance in production of the figures and manuscript.
References (72)
- et al.
Attention and distraction: effects on gut perception
Gastroenterology
(1997) - et al.
Effects of 5-hydroxy-tryptamine on discharge of vagal mucosal afferent fibres from the upper gastrointestinal tract of the ferret
J. Auton. Nerv. Syst.
(1993) - et al.
C-fos expression in specific rat brain nuclei after intestinal anaphylaxis: Involvement of 5-HT3 receptors and vagal afferent fibers
Brain Res.
(1995) - et al.
Thoracic esophageal mechanoreceptors connected with fibers following sympathetic pathways
Brain Res. Bull.
(1983) - et al.
Somatic stimulation reduces perception of gut distention in humans
Gastroenterology
(1994) - et al.
Neurochemical classification of myenteric neurons in the guinea-pig ileum
Neuroscience
(1996) - et al.
Distension-induced secretion in the rat colon: Mediation by prostaglandins and submucosal neurons
Eur. J. Pharmacol.
(1990) - et al.
Electrophysiologic properties and role of vagal thermoreceptors of lower esophagus and stomach of cat
Gastroenterology
(1982) - et al.
Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine
Gastroenterology
(1996) - et al.
Intrinsic primary afferent neurons of the intestine
Prog. Neurobiol.
(1998)
Tachykinins in the gut. Part 2. Roles in neural excitation, secretion and inflammation
Pharmacol. Ther.
Vagal unitary responses to intestinal amino acid infusions in the anaesthetised cat: a putative signal for protein induced satiety
Physiol. Behav.
Identification of sensory nerve cells in a peripheral organ (the intestine) of a mammal
Neuroscience
Neurotrophic factors and pain
Neuroscience
Nerve growth factor and nociception
Trends Neurosci.
Osmosensitive vagal receptors in the small intestine of the cat
J. Auton. Nerv. Syst.
Vagal receptors sensitive to lipids in the small intestine of the cat
J. Auton. Nerv: Syst.
Reflex changes in circular muscle activity elicited by stroking the mucosa: An electrophysiological analysis in the isolated guinea-pig ileum
J. Auton. Nerv. Syst.
GP130 cytokines, leukemia inhibitory factor and interleukin-6, induce neuropeptide expression in intact adult rat sensory neurons in vivo: time-course, specificity and comparison with sciatic nerve axotomy
Neuroscience
Mucosal distortion by compression elicits polarized reflexes and enhances responses of the circular muscle to distension in the small intestine
J. Auton. Nerv. Syst.
Analysis of the responses of myenteric neurons in the small intestine to chemical stimulation of the mucosa
Am. J. Physiol.
The effect of sympathectomy on abdominal pain in man
Gastroenterology
Effects of cholecystokinin (CCK-8) on two classes of gastroduodenal vagal afferent fibre
J. Auton. Nerv. Syst.
Locally and reflexly mediated effects of cholecystokinin-octapeptide on the ferret stomach
J. Auton. Nerv. Syst.
The immune system
Gastrointestinal hormones
Correlation between membrane potential, spike discharge and tension in smooth muscle
J. Physiol.(Lond.)
The involvement of intramural nerves in cholera toxin induced intestinal secretion
Acta Physiol. Scand.
Mucosal receptors in the gastric antrum and small intestine of the rat with afferent fibres in the cervical vagus
J. Physiol. (Lond.)
Morphological relationships of choleragenoid horseradish peroxidase-labeled spinal primary afferents with myenteric ganglia and mucosal associated lymphoid tissue in the cat esophagogastric junction
J. Comp. Neurol.
Neural regulation of intestinal electrolyte transport
Mechanoreceptors of the rabbit duodenum
Q.J. Exp. Physiol.
Mucosal enteroreceptors with vagal afferent fibres in the proximal duodenum of the sheep
J. Physiol. (Lond.)
Excitatory input from the distal colon to the inferior mesenteric ganglion in the guinea-pig
J. Physiol. (Lond.)
Über den Bau der Ganglien in den Geflechten des Darmes und der Gallenblase des Menschen und der Säugetiere
Arch. Anat. Physiol. (Leipzig), Anat. Abt. Jg.
Gastric and duodenal mucosal secretion of bicarbonate
Cited by (19)
Direct Peripheral Nerve Stimulation for the Treatment of Complex Regional Pain Syndrome: A 30-Year Review
2021, NeuromodulationCitation Excerpt :Careful sensory testing of the affected area will invariably elicit an exaggerated response from the skin that exceeds the neural innervation of one, or at most, two major nerves. This premise suggests that central summation, locally by axon reflex or other mechanisms, enables PNS to address to a greater degree of what is otherwise pain that is experienced in an expanded field of innervation or perhaps the entire distal extremity (28,29). We have demonstrated that PNS on a specific single nerve or two nerves in the upper or lower extremities can significantly reduce neuropathic pain symptoms that are associated with CRPS.
Gastrointestinal Hormones and Neurotransmitters
2010, Sleisenger and Fordtran’s Gastrointestinal and Liver Disease- 2 Volume Set: Pathophysiology, Diagnosis, Management, Expert Consult Premium Edition - Enhanced Online Features and PrintChemical stimulation of vagal afferent neurons and sympathetic vasomotor tone
2003, Brain Research ReviewsInteraction between endocrine and immune systems in fish
2002, International Review of CytologyGastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain
2001, European Journal of Pharmacology