The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration

• Published in: Neuroscience letters Vol. 568; pp. 6 - 11
• Main Authors: Sun, Yong-Hai, Li, Hong-Shi, Zhu, Chao, Hu, Wei, Yang, Jing, Zhao, Guo-Li, Lu, Gui-Jun, Wu, Sheng-Xi, Dong, Yu-Lin
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 07.05.2014
• Subjects: Adrenergic alpha-2 Receptor Antagonists - pharmacology; Analgesics - administration & dosage; Analgesics - therapeutic use; Animals; Duloxetine; Duloxetine Hydrochloride; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; Idazoxan - pharmacology; Injections, Intraperitoneal; Injections, Spinal; Ketanserin - pharmacology; Male; Mechanical hypersensitivity; Microdialysis; Norepinephrine - metabolism; Pain, Postoperative - drug therapy; Pain, Postoperative - metabolism; Pain, Postoperative - physiopathology; Post-operative pain; Rats, Sprague-Dawley; Serotonin - metabolism; Serotonin 5-HT2 Receptor Antagonists - pharmacology; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - therapeutic use; Serotonin-norepinephrine reuptake inhibitors; Spinal Cord - metabolism; Thiophenes - administration & dosage; Thiophenes - therapeutic use; Post-operative pain; Serotonin-norepinephrine reuptake inhibitors; Duloxetine; Mechanical hypersensitivity
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2014.03.046

•We modeled a post-operative pain.•Duloxetine delivery produced an anti-hyperalgesic effect in postoperative pain model.•The effect of duloxetine was partly attenuated by antagonists for 5-HT2A or α2-noradrenergic receptors.•5-HT and NA concentrations at the spinal dorsal horn were increased after duloxetine injection. 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.