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The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration.
Neurosci Lett. 2014 May 07; 568:6-11.NL

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+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24686187

Citation

Sun, Yong-Hai, et al. "The Analgesia Effect of Duloxetine On Post-operative Pain Via Intrathecal or Intraperitoneal Administration." Neuroscience Letters, vol. 568, 2014, pp. 6-11.
Sun YH, Li HS, Zhu C, et al. The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration. Neurosci Lett. 2014;568:6-11.
Sun, Y. H., Li, H. S., Zhu, C., Hu, W., Yang, J., Zhao, G. L., Lu, G. J., Wu, S. X., & Dong, Y. L. (2014). The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration. Neuroscience Letters, 568, 6-11. https://doi.org/10.1016/j.neulet.2014.03.046
Sun YH, et al. The Analgesia Effect of Duloxetine On Post-operative Pain Via Intrathecal or Intraperitoneal Administration. Neurosci Lett. 2014 May 7;568:6-11. PubMed PMID: 24686187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration. AU - Sun,Yong-Hai, AU - Li,Hong-Shi, AU - Zhu,Chao, AU - Hu,Wei, AU - Yang,Jing, AU - Zhao,Guo-Li, AU - Lu,Gui-Jun, AU - Wu,Sheng-Xi, AU - Dong,Yu-Lin, Y1 - 2014/03/28/ PY - 2014/01/09/received PY - 2014/03/11/revised PY - 2014/03/19/accepted PY - 2014/4/2/entrez PY - 2014/4/2/pubmed PY - 2014/12/15/medline KW - Duloxetine KW - Mechanical hypersensitivity KW - Post-operative pain KW - Serotonin-norepinephrine reuptake inhibitors SP - 6 EP - 11 JF - Neuroscience letters JO - Neurosci Lett VL - 568 N2 - 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. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/24686187/The_analgesia_effect_of_duloxetine_on_post_operative_pain_via_intrathecal_or_intraperitoneal_administration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(14)00245-6 DB - PRIME DP - Unbound Medicine ER -