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Title: | Effect of naltrexone on neuropathic pain in mice locally transfected with the mutant mu-opioid receptor gene in spinal cord |
Authors: | Kao, JH;Gao, MJ;Yang, PP;Law, PY;Loh, HH;Tao, PL |
Contributors: | Center for Neuropsychiatric Research |
Abstract: | Background and PurposeOpioid antagonists, such as naloxone and naltrexone, exhibit agonistic properties at the mutated receptor, MOR-S196ACSTA. In our previous study, systemic naloxone (10mg<bold>kg(</bold>-1), s.c.) elicited antinociceptive effect without the induction of tolerance, dependence or rewarding effect in mice 2weeks after intrathecal administration of double-stranded adeno-associated virus-MOR-S196ACSTA-eGFP. Here, we have investigated if this antinociceptive paradigm would be effective in a mouse model of neuropathic pain. Experimental ApproachSpinal nerves were ligated in male C57BL/6 mice 3 or 4weeks after intrathecal injection of the lentivirus encoding the construct of MOR-S196ACSTA-eGFP (LV-MOR-S196ACSTA). Anti-allodynic effects of daily s.c.injections of saline, naltrexone (10mg<bold>kg(</bold>-1)) or morphine (10mg<bold>kg(</bold>-1)) were assessed by the von Frey test. After 14days of treatment with saline, naltrexone or morphine, signs of natural withdrawal were measured at 22 and 46h after the last injection. To determine the rewarding effects induced by morphine or naltrexone, the conditioned place preference test was carried out. Key ResultsAnti-allodynic effects, as measured by von Frey test, increased after naltrexone or morphine treatment in mice transfected with LV-MOR-S196ACSTA in the spinal cord. Cessation of treatment with morphine, but not naltrexone, induced natural withdrawal and rewarding effects. Conclusions and ImplicationsSystemic injection of naltrexone after the expression of a mutant opioid receptor, MOR-S196ACSTA, in the spinal cord may have therapeutic potential for chronic neuropathic pain, without the development of dependence or addiction. Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit |
Date: | 2015-01 |
Relation: | British Journal of Pharmacology. 2015 Jan;172(2):630-641. |
Link to: | http://dx.doi.org/10.1111/bph.12790 |
JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0007-1188&DestApp=IC2JCR |
Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000346826500034 |
Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84920195093 |
Appears in Collections: | [陶寶綠] 期刊論文
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