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.
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Authors | Suneeta Tumati, Tally Largent Milnes, Henry I Yamamura, Todd W Vanderah, William R Roeske, Eva V Varga |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 601
Issue 1-3
Pg. 207-8
(Dec 28 2008)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 18976650
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Analgesics, Opioid
- RNA, Small Interfering
- Morphine
- Proto-Oncogene Proteins c-raf
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Topics |
- Analgesics, Opioid
(administration & dosage, adverse effects)
- Animals
- Drug Administration Schedule
- Hot Temperature
- Hyperalgesia
(chemically induced, prevention & control)
- Injections, Spinal
- Male
- Morphine
(administration & dosage, adverse effects)
- Proto-Oncogene Proteins c-raf
(antagonists & inhibitors)
- RNA, Small Interfering
(administration & dosage)
- Rats
- Rats, Sprague-Dawley
- Spinal Cord
(drug effects, metabolism)
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