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Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
The State Key Laboratory of Medical Neurobiology, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, P.R. China
* Author to whom correspondence should be addressed.
Received: 10 February 2009; in revised form: 23 February 2009 / Accepted: 25 February 2009 / Published: 5 March 2009
Abstract: Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance.
Keywords: β-Arrestin 2; Lentivirus; Periaqueductal gray; Analgesia; Morphine
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Li, Y.; Liu, X.; Liu, C.; Kang, J.; Yang, J.; Pei, G.; Wu, C. Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter. Int. J. Mol. Sci. 2009, 10, 954-963.
Li Y, Liu X, Liu C, Kang J, Yang J, Pei G, Wu C. Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter. International Journal of Molecular Sciences. 2009; 10(3):954-963.
Li, Yuting; Liu, Xing; Liu, Chang; Kang, Jiuhong; Yang, Jingyu; Pei, Gang; Wu, Chunfu. 2009. "Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter." Int. J. Mol. Sci. 10, no. 3: 954-963.