title: Blockade of 5-HT2A receptors at the site of inflammation inhibits activation of spinal dorsal horn neurons in rats.
abstract: Repeated inflammation in the periphery is a major cause of chronic inflammatory pain. We have showed that blockade of 5-HT2A receptors in the periphery inhibits repeated inflammation-induced pain hypersensitivity. The present study investigated whether inhibition of 5-HT2A receptor signaling at the site of inflammation could inhibit repeated inflammation-induced neurochemical changes in spinal dorsal horn neurons. Treatment with the 5-HT2A receptor antagonist ketanserin (20μg) in the hindpaw following intraplantar injection of carrageenan inhibited the increase in nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity, a marker of nitric oxide synthase (NOS), in the spinal dorsal horn. Administration of formalin (1%) in the hindpaw following the carrageenan injection evoked a great increase in NADPH-d reactivity in spinal dorsal horn neurons on the ipsilateral and contralateral sides. These changes were abolished by the pretreatment of ketanserin (20μg). The ketanserin treatment also reduced the repeated inflammation-induced expression of protein kinase gamma (PKCγ) in the membrane of spinal dorsal horn neurons and increased PKCγ protein level in the cytosol. Following the treatment with the opioid receptor antagonist naloxone methiodide (5mg/kg, s.c.), the administration of ketanserin failed to inhibit the repeated inflammation-induced increase in NADPH-d reactivity and c-Fos expression in the spinal dorsal horn. These results suggest that 5-HT2A receptor bioactivity in the inflammatory site plays an important role in repeated inflammation-induced central sensitization. The present study supports the notion that targeting 5-HT2A receptors in the periphery can be a promising therapy for relieving chronic inflammatory pain.
authors.affiliation: College of Life Sciences, Fujian Normal University, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: College of Life Sciences, Fujian Normal University, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350117, People's Republic of China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Cai
authors.affiliation: College of Life Sciences, Fujian Normal University, People's Republic of China. Electronic address: dmwang@fjnu.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Fujian Normal University, People's Republic of China. Electronic address: yhong@fjnu.edu.cn.
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007650:Ketanserin / Q000633:toxicity; D008297:Male; D009245:NADH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020671:Posterior Horn Cells / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D002351:Carrageenan; D007650:Ketanserin; D019001:Nitric Oxide Synthase; D009245:NADH Dehydrogenase; C087857:protein kinase C gamma; D011493:Protein Kinase C
keywords: 5-HT(2A) receptors; Endogenous opioid mechanism; Inflammatory pain; Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity; Protein kinase gamma (PKCγ); c-Fos