alexa A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice.
Physicaltherapy & Rehabilitation

Physicaltherapy & Rehabilitation

International Journal of Physical Medicine & Rehabilitation

Author(s): Khasar SG, Wang D, Hundle B, Aley KO, Lin YH

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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.

This article was published in Neuron. and referenced in International Journal of Physical Medicine & Rehabilitation

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