Antinociceptive potentiation and attenuation of tolerance by intrathecal β-arrestin 2 small interfering RNA in rats

C. H. Yang, H. W. Huang, K. H. Chen, Y. S. Chen, S. M. Sheen-Chen, C. R. Lin

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Abstract

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 β-arrestin 2 would reduce tolerance to chronic morphine use and the severity of precipitated morphine withdrawal. Methods. Intrathecal β-arrestin 2 (2 μg siRNA per 10 μl 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 β-arrestin 2 siRNA on antinociception and tolerance to morphine. Naloxone withdrawal (2 mg 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 β-arrestin 2 siRNA compared with the control group (morphine alone). In the probe response test, rats receiving morphine infusion with β-arrestin 2 siRNA treatment showed a significant left shift in their doseresponse 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 β-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 β-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.

Original languageEnglish
Pages (from-to)774-781
Number of pages8
JournalBritish Journal of Anaesthesia
Volume107
Issue number5
DOIs
Publication statusPublished - Nov 2011
Externally publishedYes

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Keywords

  • analgesics opioid, morphine
  • injections, spinal
  • substance withdrawal syndrome
  • β-arrestin 2

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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