Antagonism of 5-HT sub(2A) receptors inhibits the expression of pronociceptive mediator and enhances endogenous opioid mechanism in carrageenan-induced inflammation in rats
We have recently reported that treatment with the 5-HT sub(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 in...
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Veröffentlicht in: | European journal of pharmacology 2011-03, Vol.654 (1), p.33-41 |
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Sprache: | eng |
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Zusammenfassung: | We have recently reported that treatment with the 5-HT sub(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 sub(2A) receptors. Intraplantar injection of ketanserin (20 mu g) inhibited carrageenan-induced increase in CGRP immunoreactivity-positive neurons in DRG. On the other hand, administration of ketanserin (20 mu g) and 5-HT (10 mu g), but not vehicle, enhanced and inhibited recruitment of beta -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 mu -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 sub(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 sub(2A) receptors in the site of inflammation may be a promising approach to inhibit inflammatory pain. |
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ISSN: | 0014-2999 |
DOI: | 10.1016/j.ejphar.2010.12.007 |