title: Intrathecal nefopam-induced antinociception through activation of descending serotonergic projections involving spinal 5-HT7 but not 5-HT3 receptors.
abstract: We examined the involvement of spinal 5-HT(5-hydroxytryptamine) receptor 3(5-HT3R) and 7(5-HT7R) as well as the overall role of descending serotonergic projections in the analgesic effects of intrathecal(i.t.) nefopam for two rat models of formalin and paw incision test. I.t. nefopam produced an antinociceptive effect in a dose-dependent manner in both tests. Lesioning the spinal serotonergic projections using i.t. 5,7-dihydroxytryptamine(5,7-DHT) did not influence the intensity of allodynia in the paw incision test, but i.t. 5,7-DHT abolished the effect of nefopam. In the formain test, i.t. 5,7-DHT alone significantly diminished the flinches, but the effect of nefopam was not affected by i.t. 5,7-DHT. Antagonism study showed that i.t. 5-HT7R antagonist, SB269970 significantly blocked the antinociceptive effect of nefopam in both tests, but i.t. 5-HT3R antagonist, ondansetron has no influence on the effect of nefopam. The present study demonstrates that descending spinal serotonergic projections play a vital role in antinociceptive effect of i.t. nefopam in the paw incision test, but indeterminate in the formalin test. In both tests, the antinociceptive effect of i.t. nefopam involves the spinal 5-HT7R, but not 5-HT3R.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, South Korea.
authors.forename: Hyung Gon
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, South Korea.
authors.forename: Woong Mo
authors.initials: WM
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, South Korea.
authors.forename: Joung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, South Korea.
authors.forename: Hong-Beom
authors.initials: HB
authors.lastname: Bae
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, South Korea; Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: jichoi@jnu.ac.kr.
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D007278:Injections, Spinal; D008297:Male; D009340:Nefopam / Q000494:pharmacology* / Q000627:therapeutic use; D017294:Ondansetron / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000700:Analgesics; D010636:Phenols; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D017294:Ondansetron; D009340:Nefopam
keywords: 5-HT3 receptor; 5-HT7 receptor; Antinociception; Formalin; Incision; Nefopam; Serotonin; Spinal cord