國家衛生研究院 NHRI:Item 3990099045/8260
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    题名: Treatment of skin cancer pain with naltrexone in mice locally transfected with a mutant mu-opioid receptor gene in spinal cord
    作者: Tao, PL;Kung, WH;Kao, JH;Yang, PP;Law, PY;Loh, HH
    贡献者: Center for Neuropsychiatric Research
    摘要: Objective: The opioid antagonists, such as naloxone or naltrexone, exhibited full agonistic properties in the mutated mu-opioid receptor, MORS196ACSTA, in which the conserved Ser196, Thr327, Cys330 were mutated to Ala, Ala, and Ser, respectively. In our previous study, systemic naltrexone (10 mg/kg, s.c.) elicited anti-allodynic effect without the induction of dependence and rewarding effect in mice with neuropathic pain after the expression of MORS196ACSTA in the spinal cord by intrathecal administration of lentivirus (LV)-MORS196ACSTA-EGFP. The objective of this study was to further investigate whether this antinociceptive paradigm could be effective in mice with skin cancer pain. Methods: LV-MORS196ACSTA-EGFP was injected intrathecally into the male C57BL/6 mice and allowed the gene expression for 4 weeks. B16-F1 melanoma cells were then subcutaneously injected into the plantar region of left hind paw to induce skin cancer pain. The volume of paw, spontaneous pain and mechanical allodynia (determined by von Frey test) were assessed before and after systemic naltrexone (10 mg/kg, s.c.) or local naltrexone (10 nmol, i.t.) from day 5 to 18 after injection of melanoma cells. Results: The injection of melanoma cells into a hind paw of mice increased the paw volume and induced spontaneous pain and allodynia (decrease of paw withdrawal pressure) in the ipsilateral paw from day 5 to day 18. Naltrexone (10 mg/kg, s.c. or 10 nmol, i.t.) elicited significant anti-allodynic effect and improved the spontaneous pain on ipsilateral hind paws of mice which expressed MORS196ACSTA in the spinal cord. Conclusion: These data imply that naltrexone may have therapeutic potential for skin cancer pain after the gene expression of MORS196ACSTA in the spinal cord.
    日期: 2014-06
    關聯: International Journal of Neuropsychopharmacology. 2014 Jun;17(S1):73.
    Link to: http://dx.doi.org/10.1017/S1461145714000741
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1461-1457&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000339769200290
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