5-Hydroxytryptamine-induced synovial plasma extravasation is mediated via 5-hydroxytryptamine2A receptors on sympathetic efferent terminals.
5-Hydroxytryptamine (5-HT) is known to act in peripheral tissues to produce pain and inflammation, yet the mechanisms underlying 5-HT-induced inflammation have not been well studied. The present study uses a rat knee joint model of inflammation (synovial plasma extravasation) and molecular biological techniques to determine the site of action of 5-HT and the specific 5-HT receptor subtype mediating synovial 5-HT-induced plasma extravasation. 5-HT (1 microM) stimulates synovial plasma extravasation 7-fold above base-line levels. Surgical lumbar sympathectomy, but not C-fiber depletion by neonatal capsaicin, dramatically reduces 5-HT-induced synovial plasma extravasation (P < .001), indicating that sympathetic efferents mediate this effect. Polymerase chain reaction amplification of 5-HT receptor cDNA demonstrates that 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A and 5-HT3, but not the 5-HT2C, receptor subtypes are present in lumbar sympathetic ganglia. With selective ligands for these receptor subtypes, we demonstrate that 5-HT-induced synovial plasma extravasation is mediated via the 5-HT2A receptor. These findings suggest a role for 5-HT2A antagonists in various synovial inflammatory pain states.
Pierce
P A
PA
Department of Anesthesia, University of San Francisco, California, USA.
Xie
G X
GX
Peroutka
S J
SJ
Green
P G
PG
Levine
J D
JD
D000818:Animals; D001483:Base Sequence; D004487:Edema / Q000209:etiology*; D005070:Evans Blue; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000648:ultrastructure*; D009476:Neurons, Efferent / Q000648:ultrastructure*; D017933:Peripheral Nervous System / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000145:classification / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000633:toxicity*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure*; D013582:Synovial Fluid / Q000187:drug effects* / Q000378:metabolism; D013585:Synovitis / Q000097:blood
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin; D005070:Evans Blue