Antagonism of 5-HT(2A) receptors inhibits the expression of pronociceptive mediator and enhances endogenous opioid mechanism in carrageenan-induced inflammation in rats.
Eur J Pharmacol
; 654(1): 33-41, 2011 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-21185821
ABSTRACT
We have recently reported that treatment with the 5-HT(2A) receptor antagonist ketanserin in the inflamed paw raises the nociceptive threshold above normal level (hypoalgesia) and this response is naloxone-reversible. The present study aimed to investigate neurochemical changes at the site of inflammation and in dorsal root ganglia (DRG) and the spinal cord following the blockade of 5-HT(2A) receptors. Intraplantar injection of ketanserin (20 µg) inhibited carrageenan-induced increase in CGRP immunoreactivity-positive neurons in DRG. On the other hand, administration of ketanserin (20 µg) and 5-HT (10 µg), but not vehicle, enhanced and inhibited recruitment of ß-endorphin-expressing immune cells, respectively, in subcutaneous loci of inflamed hindpaw. Moreover, the treatment with ketanserin increased the number of endomorphine-containing cells in the inflamed paw and µ-opioid receptor-expressing neurons in DRG at L4-5 but reduced the expression of endomorphine in superficial layers of the lumbar spinal cord. The present study provided evidence at the cellular level showing that the blockade of 5-HT(2A) receptors inhibited inflammation-associated increase in pronociceptive mediator, and that the pronociceptive property of 5-HT is mediated by the suppression of inflammation-activated opioid mechanism. Therefore, targeting the 5-HT(2A) receptors in the site of inflammation may be a promising approach to inhibit inflammatory pain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ketanserina
/
Receptor 5-HT2A de Serotonina
/
Antagonistas do Receptor 5-HT2 de Serotonina
/
Inflamação
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article