title: Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats.
abstract: Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of tianeptine at the spinal cord level.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, Republic of Korea. Electronic address: mhyoon@chonnam.ac.kr.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea.
authors.forename: Bong Ha
authors.initials: BH
authors.lastname: Heo
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea.
authors.forename: Woong Mo
authors.initials: WM
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Gwangju Institue of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D059330:GABAergic Neurons / Q000187:drug effects* / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007278:Injections, Spinal; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010636:Phenols / Q000494:pharmacology; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries; D013449:Sulfonamides / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D014110:Touch; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000700:Analgesics; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013841:Thiazepines; C104425:serotonin 7 receptor; C050504:tianeptine; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: 5-HT(7) receptor-GABAergic interneuron-GAD65; Antiallodynic; Neuropathic pain; Spinal cord; Tianeptine