title: The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn.
abstract: The purpose of this study was to validate the effects of tianeptine on serotonergic and noradrenergic neurotransmission in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of intrathecally administered tianeptine on mechanical allodynia were assessed. Dihydroergocristine or yohimbine, a serotonergic or α-2 adrenergic receptor antagonists, respectively, were intrathecally administered 10min before tianeptine to investigate its mechanism of action. Additionally microdialysis studies were performed to measure the extracellular levels of serotonin (5-HT) and norepinephrine (NE) in the spinal dorsal horn following tianeptine administration. Intrathecal tianeptine significantly increased the paw withdrawal thresholds in a dose-dependent manner and the antiallodynic effect was antagonized by dihydroergocristine and yohimbine. Microdialysis studies revealed that tianeptine increased the levels of 5-HT and NE in the spinal dorsal horn. These findings suggest that tianeptine may be effective for the management of neuropathic pain and that its analgesic mechanism is exerted by increased levels of 5-HT and NE in the synaptic cleft at the spinal level.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 42 Jebongro, Donggu, Gwangju 501-757, Republic of Korea.
authors.forename: Hyung Gon
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 42 Jebongro, Donggu, Gwangju 501-757, Republic of Korea.
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 42 Jebongro, Donggu, Gwangju 501-757, Republic of Korea.
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
authors.affiliation: Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obata
authors.affiliation: Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 42 Jebongro, Donggu, Gwangju 501-757, Republic of Korea; Research Institute of Medical Sciences, Chonnam National University, Medical School, 42 Jebongro, Donggu, Gwangju 501-757, Republic of Korea. Electronic address: kimwm@jnu.ac.kr.
authors.forename: Woong Mo
authors.initials: WM
authors.lastname: Kim
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects* / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries; D009435:Synaptic Transmission; D013841:Thiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D014110:Touch
chemical_list: D018674:Adrenergic Antagonists; D000700:Analgesics; D000928:Antidepressive Agents; D012702:Serotonin Antagonists; D013841:Thiazepines; C050504:tianeptine; D012701:Serotonin; D009638:Norepinephrine
keywords: Antinociception; Intrathecal; Microdialysis; Norepinephrine; Serotonin; Tianeptine