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

Research output: Contribution to journalArticle

41 Citations (Scopus)

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

Fingerprint

Morphine
Small Interfering RNA
Naloxone
Opioid Analgesics
Tail
beta-Arrestin 1
Morphine Dependence
Substance Withdrawal Syndrome
Pain Management
Chronic Pain
Analgesia
Control Groups
Injections

Keywords

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

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Antinociceptive potentiation and attenuation of tolerance by intrathecal β-arrestin 2 small interfering RNA in rats. / Yang, C. H.; Huang, H. W.; Chen, K. H.; Chen, Y. S.; Sheen-Chen, S. M.; Lin, C. R.

In: British Journal of Anaesthesia, Vol. 107, No. 5, 11.2011, p. 774-781.

Research output: Contribution to journalArticle

Yang, C. H. ; Huang, H. W. ; Chen, K. H. ; Chen, Y. S. ; Sheen-Chen, S. M. ; Lin, C. R. / Antinociceptive potentiation and attenuation of tolerance by intrathecal β-arrestin 2 small interfering RNA in rats. In: British Journal of Anaesthesia. 2011 ; Vol. 107, No. 5. pp. 774-781.
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