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

TitleIntrathecal Raf-1-selective siRNA attenuates sustained morphine-mediated thermal hyperalgesia.
Publication TypeJournal Article
Year of Publication2008
AuthorsTumati S, Milnes TLargent, Yamamura HI, Vanderah TW, Roeske WR, Varga EV
JournalEur J Pharmacol
Date Published2008 Dec 28
KeywordsAnalgesics, Opioid, Animals, Drug Administration Schedule, Hot Temperature, Hyperalgesia, Injections, Spinal, Male, Morphine, Proto-Oncogene Proteins c-raf, Rats, Rats, Sprague-Dawley, RNA, Small Interfering, Spinal Cord

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.

Alternate JournalEur. J. Pharmacol.
PubMed ID18976650
PubMed Central IDPMC2640499
Grant ListR01 GM065465-04 / GM / NIGMS NIH HHS / United States
Faculty Member Reference: 
Tally Largent-Milnes, PhD
Todd Vanderah, PhD