科研之友
微信
新浪微博
Facebook
分享链接
摘要
Background. Tolerance to the analgesic effect of opioids complicates the management of persistent pain states. We tested whether the intrathecal infusion of small interfering RNA (siRNA) against beta-arrestin 2 would reduce tolerance to chronic morphine use and the severity of precipitated morphine withdrawal. Methods. Intrathecal beta-arrestin 2 (2 mu g siRNA per 10 mu l per rat) was injected once daily for 3 days. Rats then received a continuous intrathecal infusion of morphine (2 nmol h(-1)) or saline for 7 days. Daily tail-flick (TF) and intrathecal morphine challenge tests were performed to assess the effect of intrathecal beta-arrestin 2 siRNA on antinociception and tolerance to morphine. Naloxone withdrawal (2mg kg(-1)) was performed to assess morphine dependence. Results. In the daily TF test, the antinociception of intrathecal morphine was increased and maintained in rats receiving beta-arrestin 2 siRNA compared with the control group (morphine alone). In the probe response test, rats receiving morphine infusion with beta-arrestin 2 siRNA treatment showed a significant left shift in their dose-response curve, as measured by per cent maximal possible effect (MPE), such that the AD(50) was significantly decreased by a factor of 5.6 when compared with that of morphine-infused rats. In the naloxone-induced withdrawal tests, rats receiving beta-arrestin 2 siRNA injection with morphine infusion showed a significant reduction in four of the six signs of withdrawal. Conclusions. We show here that intrathecal beta-arrestin 2 siRNA in rats enhances analgesia and attenuates naloxone-induced withdrawal symptoms. This may warrant further investigation in the context of long-term use of intrathecal opioids for controlling chronic pain.
- 出版日期2011-11
- 单位长春大学; 中山大学
