Article Text

Capsaicin sensitivity and epidermal growth factor
  1. CURE Digestive Disease Research Centre, UCLA,
  2. 11301 Wiltshire Blvd, Bldg 115,
  3. Los Angeles, CA 90073, USA

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

See article on page344

It is now well established that afferent neurones innervating the intestine subserve “effector” as well as sensory functions. The release of neuromodulators from the peripheral nerve terminals of extrinsic afferents has been shown to play a role in the regulation of blood flow and secretory and motor functions of the gastrointestinal tract.1 In animals (but not in humans) most of the extrinsic spinal sensory neurones express calcitonin gene related peptide (CGRP) or substance P, or both.2 The role of afferent neurones and these neuropeptides in the regulation of gastric mucosal integrity has received much attention. Experimental injury in the rat stomach induced by pyloric ligation or injurious factors, such as hydrochloric acid, taurocholate, aspirin, and ethanol, is reduced by stimulation of extrinsic afferent nerve terminals by intragastric administration of capsaicin prior to the injurious agent. In addition, intragastric administration of capsaicin increases gastric mucosal blood flow (GMBF). This protective effect of capsaicin and the increase in GMBF is mimicked by close arterial administration of CGRP and blocked by either functional sensory denervation by neurotoxic doses of capsaicin, or by administration of a CGRP-1 receptor antagonist, CGRP8–37, and by immunoblockade with polyclonal or monoclonal antibodies to CGRP.3

Epidermal growth factor (EGF) protects against gastric mucosal injury in experimental animals and humans. In the study by Kang et al (see page 344), evidence is provided to support the hypothesis that EGF acts via capsaicin sensitive afferent neurones and release of CGRP, presumably from peripheral nerve terminals. The protective effect of EGF was abolished by functional sensory denervation. In anaesthetised rats, EGF produced a capsaicin sensitive, CGRP-1 receptor dependent increase in GMBF, an effect which may account for protection against gastric mucosal injury. The authors conclude that EGF increases GMBF by an action on spinal sensory neurones that results in release of CGRP and vasodilatation of arterioles.

These data confirm observations published in abstract form by two other groups, and this interesting study is important for several reasons. It provides solid evidence that an endogenous extragastric agent, EGF, acts via gastric spinal afferent neurones and CGRP to influence gastric mucosal integrity. However, no evidence is presented for a role for endogenous EGF. Thus, in animals with an intact sensory innervation, sialoadenectomy had no effect on the amount of damage caused by ethanol. As the authors point out, the use of absolute ethanol to produce lesions may be too severe a stimulus to show a protective role of endogenous EGF. In this and many other published studies, functional ablation of capsaicin sensitive neurones had no effect on basal GMBF nor on mucosal integrity. In addition, the use of a single dose of EGF does not allow for full comparison or evaluation of the effect of EGF. It must also be considered that mechanisms other than a hyperaemia, such as inhibition of gastric acid secretion, may be responsible for protecting the mucosa. It should be noted that although the data are consistent with a role for CGRP, CGRP8–37 has also been shown to antagonise the effects of amylin (expressed by sensory neurones and gastric endocrine cells) and adrenomedullin (from endothelial cells).4 ,5 The role of these peptides in afferent nerve mediated gastric hyperaemia or mucosal protection has not been tackled.

What is the pathophysiological significance of these findings? Sensory nerve stimulation has been shown to prevent experimental injury induced by both exogenous and endogenous agents. The protective effect of sensory nerve stimulation by capsaicin and ingestion of chilli is also seen in humans.6 Ingestion of chilli powder reduced the aspirin induced damage to the human gastric mucosa assessed by both endoscopy and biopsy. As noted earlier, the human gastric mucosa does not contain neuronal CGRP7 and therefore the neuropeptide that may be responsible for mediating these effects in humans is unknown. It is interesting to speculate on the mechanism by which EGF may stimulate sensory nerve terminals, and whether this is a direct or indirect action. However, until a role for endogenous EGF is established, these remain interesting, but descriptive findings on the multiorgan modulation of function in the gastrointestinal tract.


Linked Articles