title: Effect of naltrexone on neuropathic pain in mice locally transfected with the mutant μ-opioid receptor gene in spinal cord.
abstract: OBJECTIVE
  Opioid antagonists, such as naloxone and naltrexone, exhibit agonistic properties at the mutated μ receptor, MOR-S196ACSTA. In our previous study, systemic naloxone (10 mg·kg(-1) , s.c.) elicited antinociceptive effect without the induction of tolerance, dependence or rewarding effect in mice 2 weeks 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.
  
  
  METHODS
  Spinal nerves were ligated in male C57BL/6 mice 3 or 4 weeks 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 (10 mg·kg(-1) ) or morphine (10 mg·kg(-1) ) were assessed by the von Frey test. After 14 days of treatment with saline, naltrexone or morphine, signs of natural withdrawal were measured at 22 and 46 h after the last injection. To determine the rewarding effects induced by morphine or naltrexone, the conditioned place preference test was carried out.
  
  
  RESULTS
  Anti-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
  Systemic injection of naltrexone after the expression of a mutant μ opioid receptor, MOR-S196ACSTA, in the spinal cord may have therapeutic potential for chronic neuropathic pain, without the development of dependence or addiction.
  
  
  BACKGROUND
  This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
authors.affiliation: Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jen-Hsin
authors.initials: JH
authors.lastname: Kao
authors.forename: Man-Jun
authors.initials: MJ
authors.lastname: Gao
authors.forename: Pao-Pao
authors.initials: PP
authors.lastname: Yang
authors.forename: Ping-Yee
authors.initials: PY
authors.lastname: Law
authors.forename: Horace H
authors.initials: HH
authors.lastname: Loh
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003213:Conditioning, Psychological; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009154:Mutation; D009271:Naltrexone / Q000494:pharmacology / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D012201:Reward; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013127:Spinal Nerves; D013375:Substance Withdrawal Syndrome; D014162:Transfection
chemical_list: D000700:Analgesics; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D009020:Morphine