Intrathecal Raf-1-selective siRNA attenuates sustained morphine-mediated thermal hyperalgesia.
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.
Tumati
Suneeta
S
Department of Pharmacology, University of Arizona, Tucson, AZ 85724, USA.
Milnes
Tally Largent
TL
Yamamura
Henry I
HI
Vanderah
Todd W
TW
Roeske
William R
WR
Varga
Eva V
EV
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D004334:Drug Administration Schedule; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D034741:RNA, Small Interfering; D009020:Morphine; D019908:Proto-Oncogene Proteins c-raf