Antinociceptive potentiation and attenuation of tolerance by intrathecal {beta}-arrestin 2 small interfering RNA in rats.

Authors: Yang, CH  Huang, HW  Chen, KH  Chen, YS  Sheen-Chen, SM  Lin, CR 
Citation: Yang CH, etal., Br J Anaesth. 2011 Nov;107(5):774-81. Epub 2011 Sep 17.
Pubmed: (View Article at PubMed) PMID:21926413
DOI: Full-text: DOI:10.1093/bja/aer291

BACKGROUND: /st> 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: /st> Intrathecal beta-arrestin 2 (2 mug siRNA per 10 mul 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 (2 mg kg(-1)) was performed to assess morphine dependence. RESULTS: /st> 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: /st> 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.


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CRRD Object Information
CRRD ID: 5509871
Created: 2011-11-09
Species: All species
Last Modified: 2011-11-09
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.