US EPA

1980949 

Journal Article 

The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors 

Zeitz, KP; Guy, N; Malmberg, AB; Dirajlal, S; Martin, WJ; Sun, L; Bonhaus, DW; Stucky, CL; Julius, D; Basbaum, AI 

2002 

Yes 

Journal of Neuroscience
ISSN: 0270-6474
EISSN: 1529-2401 

22 

3 

1010-1019 

11826129 

WOS:000173660800049 

http://://WOS:000173660800049
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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-HT3 receptor 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. 

serotonin; 5-HT3 receptor; inflammatory pain; primary afferent nociceptors; descending pain modulation; neurogenic inflammation