Gastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain.

Abstract:

:An intricate surveillance network consisting of enteroendocrine cells, immune cells and sensory nerve fibres monitors the luminal and interstitial environment in the alimentary canal. Functional bowel disorders are characterized by persistent alterations in digestive regulation and gastrointestinal discomfort and pain. Visceral hyperalgesia may arise from an exaggerated sensitivity of peripheral afferent nerve fibres and/or a distorted processing and representation of gut signals in the brain. Novel strategies to treat these sensory bowel disorders are therefore targeted at primary afferent nerve fibres. These neurons express a number of molecular traits including transmitters, receptors and ion channels that are specific to them and whose number and/or behaviour may be altered in chronic visceral pain. The targets under consideration comprise vanilloid receptor ion channels, acid-sensing ion channels, sensory neuron-specific Na(+) channels, P2X(3) purinoceptors, 5-hydroxytryptamine (5-HT), 5-HT(3) and 5-HT(4) receptors, cholecystokinin CCK(1) receptors, bradykinin and prostaglandin receptors, glutamate receptors, tachykinin and calcitonin gene-related peptide receptors as well as peripheral opioid and cannabinoid receptors. The utility of sensory neuron-targeting drugs in functional bowel disorders will critically depend on the compounds' selectivity of action for afferent versus enteric or central neurons.

journal_name

Eur J Pharmacol

authors

Holzer P

doi

10.1016/s0014-2999(01)01319-x

keywords:

subject

Has Abstract

pub_date

2001-10-19 00:00:00

pages

177-93

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S001429990101319X

journal_volume

429

pub_type

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