title: Intrathecal PLC(β3) 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. 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.
authors: Shanghai Sixth People's Hospital, Department of Anesthesiology, 600 Yishan Road, Shanghai 200233, China.
authors: Zhou
authors: Z
authors: Quanhong
authors: Xue
authors: X
authors: Ying
authors: Chen
authors: C
authors: Moxi
authors: Xu
authors: X
authors: Tao
authors: Wang
authors: W
authors: Jing
authors: Zhang
authors: Z
authors: Xin
authors: Wang
authors: W
authors: Li
authors: Cui
authors: C
authors: Derong
authors: Zhang
authors: Z
authors: Xiaoli
authors: Jiang
authors: J
authors: Wei
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage*; D054799:Phospholipase C beta / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D020319:Oligodeoxyribonucleotides, Antisense; D009020:Morphine; D054799:Phospholipase C beta; C518041:Plcb3 protein, rat