Effect of naltrexone on neuropathic pain in mice locally transfected with the mutant μ‐opioid receptor gene in spinal cord

Background and Purpose 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. Experimental Approach 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. Key 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 and Implications 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. Linked Articles 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