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Neurosci Lett. 2014 May 7;568:6-11. doi: 10.1016/j.neulet.2014.03.046. Epub 2014 Mar 28.

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

Author information

  • 1Anesthesia and Operation Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, PR China.
  • 2Department of Stomatology, Chinese General Air Force Hospital, No. 30 Fucheng Road, Beijing 100164, PR China.
  • 3Department of Orthopedics, Xi'jing Hospital, Fourth Military Medical University, No. 169 West Changle Road, Xi'an 710032, PR China.
  • 4Department 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.
  • 5Department 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.
  • 6Department 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.

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.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Duloxetine; Mechanical hypersensitivity; Post-operative pain; Serotonin-norepinephrine reuptake inhibitors

PMID:
24686187
[PubMed - in process]
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