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Stimulation of spinal 5-HT(2A/2C) receptors potentiates the capsaicin-induced in vivo release of substance P-like immunoreactivity in the rat dorsal horn.

Abstract：

:Stimulation of spinal serotonin (5-HT)(2A/2C) receptors has previously been reported to lead to either a pro-nociceptive or an anti-nociceptive response. Behavioral data have indicated that the pro-nociceptive effect is related to the release of substance P (SP). The aim of this in vivo microdialysis study was to investigate if stimulation of spinal 5-HT(2A/2C) receptors by the selective agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) induces spontaneous or capsaicin-evoked increase in the release of SP-like immunoreactivity (SP-LI) in the rat dorsal horn. A dose of capsaicin (25 microM in the perfusion medium administered for 30 min), which did not lead to a significant release of SP-LI on its own, induced a significant increase of greater than 4-fold of the SP-LI level following spinal application of 50 nmol DOI. Higher (500 nmol) or lower (5 nmol) doses of DOI failed to induce a similar effect. In rats with a peripheral inflammation, induced by carrageenan, capsaicin (25 microM) induced a non-significant increase of SP-LI. A significant 8-fold increase of the SP-LI level was detected following administration of 50 nmol DOI in combination with capsaicin. The effect of DOI, which was completely prevented by co-administration of the 5-HT(2A) receptor antagonist ketanserin in control animals without peripheral inflammation, was only partly blocked in animals with carrageenan induced peripheral inflammation. In conclusion, stimulation of 5-HT(2A/2C) receptors facilitates the capsaicin-evoked release of SP-LI in the dorsal horn in both animals with and without carrageenan-induced unilateral inflammation. The observation that the highest dose of DOI failed to induce SP-LI release may be due to an inhibitory postsynaptic action at this dose.

journal_name

Brain Res

journal_title

Brain research

authors

Kjørsvik Bertelsen A,Warsame Afrah A,Gustafsson H,Tjølsen A,Hole K,Stiller CO

doi

10.1016/s0006-8993(03)03216-5

subject

Has Abstract

pub_date

2003-10-10 00:00:00

pages

10-6

issue

1

eissn

0006-8993

issn

1872-6240

pii

S0006899303032165

journal_volume

987

pub_type

杂志文章

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