Intrathecal Raf-1-selective siRNA attenuates sustained morphine-mediated thermal hyperalgesia

Suneeta Tumati, Tally Largent Milnes, Henry I. Yamamura, Todd W. Vanderah, William R. Roeske, Eva V. Varga

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Studies have demonstrated that long-term opioid treatment leads to an increased sensitivity to painful (hyperalgesia) or normally innocuous (allodynia) stimuli. The molecular mechanisms that lead to paradoxical pain sensitization upon chronic opioid treatment are not completely understood. Enhanced excitatory pain neurotransmitter (such as calcitonin gene-related peptide (CGRP)) release in the dorsal horn of the spinal cord may play a role in sustained morphine-mediated paradoxical pain. Recently we have demonstrated that inhibition of Raf-1 attenuates sustained morphine treatment-mediated augmentation of CGRP release in vitro, in cultured primary sensory neurons. In the present study, we show that knockdown of spinal Raf-1 levels in vivo by intrathecal administration of Raf-1-specific siRNA attenuates sustained morphine-mediated thermal hyperalgesia in rats.

Original languageEnglish (US)
Pages (from-to)207-208
Number of pages2
JournalEuropean Journal of Pharmacology
Volume601
Issue number1-3
DOIs
StatePublished - Dec 28 2008

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Keywords

  • Hyperalgesia
  • Morphine
  • Opioids
  • Raf-1

ASJC Scopus subject areas

  • Pharmacology

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