Reversal of ongoing thermal hyperalgesia in mice by a recombinant herpesvirus that encodes human preproenkephalin.
Reversal of ongoing thermal hyperalgesia in mice by a recombinant herpesvirus that encodes human preproenkephalin.
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通过编码人前脑啡肽原的重组疱疹病毒逆转小鼠正在进行的热痛觉过敏。
DOI：
10.1016/j.ymthe.2003.10.008
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Wilson,StevenP
中科院分区：
文献类型：
--
作者：
Yeomans,DavidC;Jones,Toni;Laurito,CharlesE;Lu,Ying;Wilson,StevenP
Herpesvirus-mediated transfer of the human preproenkephalin gene to primary afferent nociceptors prevents phasic thermal allodynia/hyperalgesia in mice. It is not known, however, whether similar viral treatments would reverse ongoing or chronic pain and allodynia/hyperalgesia. To this end, mice were given intrathecal injections of pertussis toxin (PTX), which produces a weeks-long thermal hyperalgesia apparently by uncoupling certain G proteins from inhibitory neurotransmitter receptors. This treatment produced profound thermal hyperalgesia in both Aδ and C-fiber thermonociceptive tests lasting at least 6 weeks. However, treatment of skin surfaces with an enkephalin-encoding herpesvirus, but not control virus or vehicle, completely reversed this hyperalgesia. This profound antihyperalgesia was observed for both Aδ- and C-fiber-mediated responses. Interestingly, however, while the antihyperalgesic effect of the enkephalin-encoding virus on C-fiber-mediated responses was reversed by intrathecal application of μ or δ opioid antagonists, only δ antagonists reversed the effect of this virus on Aδ hyperalgesia. Thus, virus-mediated delivery of the proenkephalin cDNA reverses thermal hyperalgesia produced by PTX-induced ribosylation of inhibitory G proteins by an opioid-mediated mechanism. These results suggest that herpesvirus vectors encoding analgesic peptides may be useful in attenuating centrally mediated, ongoing neuropathic pain and/or hyperalgesia.
