PT  - JOURNAL ARTICLE
AU  - Karla P. Zeitz
AU  - Nicolas Guy
AU  - Annika B. Malmberg
AU  - Sahera Dirajlal
AU  - William J. Martin
AU  - Linda Sun
AU  - Douglas W. Bonhaus
AU  - Cheryl L. Stucky
AU  - David Julius
AU  - Allan I. Basbaum
TI  - The 5-HT<sub>3</sub> Subtype of Serotonin Receptor Contributes to Nociceptive Processing via a Novel Subset of Myelinated and Unmyelinated Nociceptors
AID  - 10.1523/JNEUROSCI.22-03-01010.2002
DP  - 2002 Feb 01
TA  - The Journal of Neuroscience
PG  - 1010--1019
VI  - 22
IP  - 3
4099  - http://www.jneurosci.org/content/22/3/1010.short
4100  - http://www.jneurosci.org/content/22/3/1010.full
SO  - J. Neurosci.2002 Feb 01; 22
AB  - Serotonin is a major component of the inflammatory chemical milieu and contributes to the pain of tissue injury via an action on multiple receptor subtypes. Here we studied mice after genetic or pharmacological disruption of the 5-HT3 receptor, an excitatory serotonin-gated ion channel. We demonstrate that tissue injury-induced persistent, but not acute, nociception is significantly reduced after functional elimination of this receptor subtype. Specifically, in the setting of tissue injury, the 5-HT3receptor mediates activation of nociceptors but does not contribute to injury-associated edema. This result is explained by the localization of 5-HT3 receptor transcripts to a previously uncharacterized subset of myelinated and unmyelinated afferents, few of which express the proinflammatory neuropeptide substance P. Finally, we provide evidence that central serotonergic circuits modulate nociceptive transmission via a facilitatory action at spinal 5-HT3 receptors. We conclude that activation of both peripheral and central 5-HT3 receptors is pronociceptive and that the contribution of peripheral 5-HT3 receptors involves a novel complement of primary afferent nociceptors.