title: Antagonism of 5-HT(2A) receptors inhibits the expression of pronociceptive mediator and enhances endogenous opioid mechanism in carrageenan-induced inflammation in rats.
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 β-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.
authors.affiliation: College of Life Sciences, Fujian Normal University, Key Provincial Laboratory of Developmental and Neurological Biology, Fuzhou, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Fan
authors.forename: Yue
authors.initials: Y
authors.lastname: Jia
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002351:Carrageenan; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D017450:Receptors, Opioid, mu; D058830:Serotonin 5-HT2 Receptor Antagonists; D012701:Serotonin; D001615:beta-Endorphin; D002351:Carrageenan; D007650:Ketanserin; D015740:Calcitonin Gene-Related Peptide