Elsevier

Neuroscience

Volume 86, Issue 2, 1 June 1998, Pages 389-398
Neuroscience

Discussion

https://doi.org/10.1016/S0306-4522(98)00047-5Get rights and content

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    Our earlier study demonstrated that TRPV1-expressing afferents monitor homeostasis, conveying this information to the CNS, and are involved in the pathophysiology of HS in a rat model.7 The efferent function of sensory nerves, mediated by the release of neuropeptides from their peripheral nerve endings, is also reported to regulate vasodilation and other tissue activities.15 To evaluate the possible involvement of TRPV1 activation in hemodynamic responses after HS, with a particular focus on its neurotransmitter release, we used the competitive TRPV1 antagonist CPZ16 and the selective CGRP antagonist hCGRP8-37.17

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    By releasing peptide transmitters in the periphery, sensory nerve fibres have the capacity to regulate vascular diameter and permeability and other tissue processes, these effects being embodied in the term neurogenic inflammation. This efferent-like mode of operation of sensory neurons may take place independently of nociception, and it has been hypothesized that some DRG neurons are specialized in controlling peripheral effector mechanisms only, while other DRG neurons may be specialized in the afferent signalling of sensation and pain (Holzer and Maggi, 1998). The neuropeptides mediating the efferent-like mode of operation comprise, among others, calcitonin gene-related peptide (CGRP) and the tachykinins substance P and neurokinin A. Acid-evoked release of CGRP, one of the most potent vasodilator peptides, has been demonstrated in a variety of tissues including the gastric mucosa (Geppetti et al., 1991; Manela et al., 1995; Auer et al., 2010).

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    These small nerve fibers arise in the skin where they serve for the detection of cold, heat and, as nociceptors, for detection of painful stimuli [4–6]. In addition, they fulfill an efferent function as part of the peripheral autonomic nervous system [3,7]. Generally, nociceptors are electrically silent; after activation by noxious stimuli an action potential is initiated and transported via peripheral axons to cell bodies located in the trigeminal- and dorsal-root ganglia (DRG) alongside the medulla and spinal column.

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    The TRPV1 agonist capsaicin and mustard oil (a TRPA1 and TRPV1 agonist) have been instrumental in discovering and analyzing this phenomenon (Holzer, 1988). The messengers involved in the efferent-like mode of operation include CGRP, somatostatin and the tachykinins substance P and neurokinin A (Maggi, 1995; Holzer & Maggi, 1998; Pintér et al., 2006). Administration of capsaicin to the esophageal, gastric and intestinal mucosa increases mucosal blood flow, a response which is mimicked by exposure to excess acid (Holzer, 1998, 2004).

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