title: Intrathecal Raf-1-selective siRNA attenuates sustained morphine-mediated thermal hyperalgesia.
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.
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Suneeta
authors.initials: S
authors.lastname: Tumati
authors.forename: Tally Largent
authors.initials: TL
authors.lastname: Milnes
authors.forename: Henry I
authors.initials: HI
authors.lastname: Yamamura
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
authors.forename: William R
authors.initials: WR
authors.lastname: Roeske
authors.forename: Eva V
authors.initials: EV
authors.lastname: Varga
mesh_terms: 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
chemical_list: D000701:Analgesics, Opioid; D034741:RNA, Small Interfering; D009020:Morphine; D019908:Proto-Oncogene Proteins c-raf