title: The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration.
abstract: One promising strategy to prevent the chronicity of post-operative pain (POP) is to attenuate acute POP during the early phase by efficacious medications with fewer side effects. Duloxetine, one of the serotonin (5-HT)-norepinephrine (NE) reuptake inhibitors (SNRI), is used to treat a wide range of acute and chronic pain. However, its effect on POP has not been investigated. In the present study, we investigated the anti-hypersensitivity effect of duloxetine using a rat model of POP. The possible involvement of spinal 5-HT2A and α2-noradrenergic receptors were also evaluated by using antagonists for 5-HT2A (ketanserin) or α2-noradrenergic receptors (idazoxan). Finally, with the method of in vivo microdialysis, the increase in spinal NA and 5-HT levels after intraperitoneal (i.p.) delivery of duloxetine were investigated. The results showed that intrathecal (i.t.) or i.p. delivery of duloxetine produced an anti-hyperalgesic effect in a dose-dependent manner. The anti-hypersensitivity effect of duloxetine was partly attenuated by pretreatment with ketanserin or idazoxane. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30min after i.p. injection of 20mg/kg duloxetine. These findings indicate that duloxetine inhibits POP by increasing spinal NA and 5-HT levels and activating spinal 5-HT2A or α2-noradrenergic receptors.
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, PR China.
authors.forename: Yong-Hai
authors.initials: YH
authors.lastname: Sun
authors.affiliation: Department of Stomatology, Chinese General Air Force Hospital, No. 30 Fucheng Road, Beijing 100164, PR China.
authors.forename: Hong-Shi
authors.initials: HS
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xi'jing Hospital, Fourth Military Medical University, No. 169 West Changle Road, Xi'an 710032, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, No. 169 West Changle Road, Xi'an 710032, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, PR China.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Zhao
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, PR China.
authors.forename: Gui-Jun
authors.initials: GJ
authors.lastname: Lu
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, No. 169 West Changle Road, Xi'an 710032, PR China. Electronic address: shengxi@fmmu.edu.cn.
authors.forename: Sheng-Xi
authors.initials: SX
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, No. 169 West Changle Road, Xi'an 710032, PR China. Electronic address: donganat@fmmu.edu.cn.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Dong
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000068736:Duloxetine Hydrochloride; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019329:Idazoxan / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism; D010149:Postoperative Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013116:Spinal Cord / Q000378:metabolism; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D000068736:Duloxetine Hydrochloride; D019329:Idazoxan; D007650:Ketanserin; D009638:Norepinephrine; D012701:Serotonin; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes
keywords: Duloxetine; Mechanical hypersensitivity; Post-operative pain; Serotonin-norepinephrine reuptake inhibitors