A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice |
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Authors: | Khasar S G Lin Y H Martin A Dadgar J McMahon T Wang D Hundle B Aley K O Isenberg W McCarter G Green P G Hodge C W Levine J D Messing R O |
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Affiliation: | Department of Internal Medicine and Oral Surgery, National Institutes of Health/University of California, USA. |
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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. |
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