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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-5-19
pubmed:abstractText
We previously reported that intrathecal pro-opiomelanocortin gene electroporation could reduce pain sensitivity induced by chronic constriction injury (CCI) of the sciatic nerve. For optimal use of antinociceptive gene therapy, it might be important to control the expression of the transfected gene extrinsically. For this purpose, a doxycycline-controlled transrepressor system composed of two plasmids coding, respectively, for pro-opiomelanocortin gene (pTRE2-POMC) and the silencer (pTel-off) was employed. The regulation of beta-endorphin expression was first assessed in spinal neuronal culture, then we electrotranfected this plasmid into the spinal cord of mononeuropathic rats and evaluated the analgesic potential of this therapy in vivo by thermal and mechanical withdrawal latency. Intraperitoneal injections of various doses of doxycycline were made to elucidate the possible exogenous downregulation of transfected beta-endorphin gene expression in vivo. The levels of beta-endorphin were analyzed by intrathecal microdialysis and radioimmunoassay. Intrathecal pTRE2-POMC/pTel-off electroporation elevated spinal beta-endorphin levels, as manifested in a significantly elevated pain threshold for chronic constriction injury limbs. Intraperitoneal doxycycline decreased the antinociceptive effect and spinal beta-endorphin levels in a dose-dependent manner. We concluded that intrathecal pTRE2-POMC/pTel-off electroporation alleviates CCI-induced limb pain, and can be controlled by intraperitoneal doxycycline administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
933-40
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Regulated, electroporation-mediated delivery of pro-opiomelanocortin gene suppresses chronic constriction injury-induced neuropathic pain in rats.
pubmed:affiliation
Department of Biological Sciences, National Sun Yat-Sen University, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't