Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance.

Journal Article (Journal Article)

Morphine is a mainstay for chronic pain treatment, but its efficacy has been hampered by physical tolerance. The underlying mechanism for chronic morphine induced tolerance is complicated and not well understood. PLC(β3) is regarded as an important factor in the morphine tolerance signal pathway. In this study, we determined intrathecal (i.t.) administration of an antisense oligodeoxynucleotide (ODN) of PLC(β3) could quicken the on-set antinociceptive efficacy of acute morphine treatment and prolong the maximum effect up to 4h. The antisense could also attenuate the development of morphine-induced tolerance and left shift the ED50 after 7 day of coadministration with morphine. These results probably were contributed by the PLC(β3) antisense ODN as they successfully knocked down protein expression levels and reduced activity of PLC(β3) in spinal cord in rats. The mismatch group had no such effects. The results confirmed the important involvement of PLC(β3) in both acute morphine efficacy and chronic morphine tolerance at spinal level in rats. This study may provide an idea for producing a novel adjuvant for morphine treatment.

Full Text

Duke Authors

Cited Authors

  • Quanhong, Z; Ying, X; Moxi, C; Tao, X; Jing, W; Xin, Z; Li, W; Derong, C; Xiaoli, Z; Wei, J

Published Date

  • September 7, 2012

Published In

Volume / Issue

  • 1472 /

Start / End Page

  • 38 - 44

PubMed ID

  • 22771399

Electronic International Standard Serial Number (EISSN)

  • 1872-6240

Digital Object Identifier (DOI)

  • 10.1016/j.brainres.2012.06.030

Language

  • eng

Conference Location

  • Netherlands