title: A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice.
abstract: There is great interest in discovering new targets for pain therapy since current methods of analgesia are often only partially successful. Although protein kinase C (PKC) enhances nociceptor function, it is not known which PKC isozymes contribute. Here, we show that epinephrine-induced mechanical and thermal hyperalgesia and acetic acid-associated hyperalgesia are markedly attenuated in PKCepsilon mutant mice, but baseline nociceptive thresholds are normal. Moreover, epinephrine-, carrageenan-, and nerve growth factor- (NGF-) induced hyperalgesia in normal rats, and epinephrine-induced enhancement of tetrodotoxin-resistant Na+ current (TTX-R I(Na)) in cultured rat dorsal root ganglion (DRG) neurons, are inhibited by a PKCepsilon-selective inhibitor peptide. Our findings indicate that PKCepsilon regulates nociceptor function and suggest that PKCepsilon inhibitors could prove useful in the treatment of pain.
authors.affiliation: Department of Internal Medicine and Oral Surgery, National Institutes of Health/University of California, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Khasar
authors.forename: Y H
authors.initials: YH
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Dadgar
authors.forename: T
authors.initials: T
authors.lastname: McMahon
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Hundle
authors.forename: K O
authors.initials: KO
authors.lastname: Aley
authors.forename: W
authors.initials: W
authors.lastname: Isenberg
authors.forename: G
authors.initials: G
authors.lastname: McCarter
authors.forename: P G
authors.initials: PG
authors.lastname: Green
authors.forename: C W
authors.initials: CW
authors.lastname: Hodge
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
authors.forename: R O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D019342:Acetic Acid; D000698:Analgesia; D000700:Analgesics; D000818:Animals; D002351:Carrageenan; D004791:Enzyme Inhibitors; D004837:Epinephrine; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D020932:Nerve Growth Factor; D009619:Nociceptors / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D015222:Sodium Channels; D013779:Tetrodotoxin; D002351:Carrageenan; D020932:Nerve Growth Factor; D011493:Protein Kinase C; D019342:Acetic Acid; D004837:Epinephrine