Intrathecal PLCβ3 oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance

Abstract

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. PLCβ3 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 PLCβ3 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 PLCβ3 antisense ODN as they successfully knocked down protein expression levels and reduced activity of PLCβ3 in spinal cord in rats. The mismatch group had no such effects. The results confirmed the important involvement of PLCβ3 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.