Gastroenterology

Gastroenterology

Volume 114, Issue 4, April 1998, Pages 823-839
Gastroenterology

Special Reports and Reviews
Neural emergency system in the stomach,☆☆

https://doi.org/10.1016/S0016-5085(98)70597-9Get rights and content

Abstract

The maintenance of gastric mucosal integrity depends on the rapid alarm of protective mechanisms in the face of pending injury. Afferent neurons of extrinsic origin constitute an emergency system that is called into operation when the gastric mucosa is endangered by acid and other noxious chemicals. The function of these chemoceptive afferents can be manipulated selectively and explored with the excitotoxin capsaicin. Most of the homeostatic actions of capsaicin-sensitive afferents are brought about by peptides released from their peripheral endings in the gastric wall. When stimulated, chemoceptive afferents enhance gastric blood flow and activate hyperemia-dependent and hyperemia-independent mechanisms of protection and repair. In the rodent stomach, these local regulatory roles of sensory neurons are mediated by calcitonin gene-related peptide acting via calcitonin gene-related peptide 1 receptors and neurokinin A acting via neurokinin 2 receptors, with both peptides using nitric oxide as their common messenger. In addition, capsaicin-sensitive neurons form the afferent arc of autonomic reflexes that control secretory and motor functions of the stomach. The pathophysiological potential of the neural emergency system is best portrayed by the gastric hyperemic response to acid backdiffusion, which is signaled by afferent nerve fibers. This mechanism limits damage to the surface of the mucosa and creates favorable conditions for rapid restitution and healing of the wounded mucosa.

GASTROENTEROLOGY 1998;114:823-839

Section snippets

Innervation of the stomach by extrinsic afferent nerve fibers

The extrinsic afferent nerve fibers supplying the stomach arise from two different sources (Figure 1).

. Innervation of the mammalian stomach by extrinsic primary afferent neurons. Afferent neurons in the vagus nerves originate from the nodose ganglia, whereas afferent neurons in the splanchnic nerves have their cell bodies in the dorsal root ganglia.

The spinal sensory neurons originate from cell bodies in the dorsal root ganglia and reach the stomach via the splanchnic and mesenteric nerves,

Vasodilation caused by afferent neuron stimulation

Stimulation of afferent nerve fibers by short-term intragastric administration of capsaicin causes a marked increase in gastric mucosal blood flow (GMBF; Table 2).14, 15, 16, 17, 18 This effect is brought about by dilation of submucosal arterioles, but not venules,17 and depends on the integrity of the extrinsic afferent innervation of the stomach, because pretreatment of rats with a neurotoxic dose of capsaicin prevents the hyperemic response to sensory neuron stimulation.15 Nerve-selective

Enhancement of gastric mucosal vulnerability by sensory neuron ablation

The ability of sensory neurons to strengthen gastric mucosal resistance to damage was first envisaged when Szolcsányi and Barthó56 discovered that capsaicin-induced ablation of afferent neurons aggravated gastric injury caused by pylorus ligation. Subsequent studies have proved that pretreatment of rats with a neurotoxic dose of capsaicin does not cause damage by itself40, 47, 89, 90, 91 but exacerbates mucosal lesion formation caused by injurious factors such as water immersion restraint

Capsaicin-sensitive afferents as neural emergency system

Although capsaicin-sensitive afferent neurons participate in the physiological regulation of gastric functions, their primary role is to operate as a neural emergency system that is called into operation in the face of pending injury to the stomach but is not tonically active (Figure 6).

. Schematic diagram of the physiological and pathophysiological implications of the neural emergency system in the stomach.

As a result, blood flow to the stomach is greatly augmented, an effect that facilitates

Acknowledgements

The author thanks Dr. Ulrike Holzer-Petsche for drawing the computer graphs.

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    Address requests for reprints to: Peter Holzer, Ph.D., Department of Experimental and Clinical Pharmacology, University of Graz, Universitätsplatz 4, A-8010 Graz, Austria. Fax: (43) 316-380-9645.

    ☆☆

    Work performed in the author's laboratory was supported by grants 7845, 9473, 9823, and 11834 from the Austrian Science Foundation; grants 4207, 4905, and 6237 from the Austrian National Bank; and by the Franz Lanyar Foundation at the Medical Faculty of the University of Graz.

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