Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

PLC-β3 signals upstream of PKCε in acute and chronic inflammatory hyperalgesia

Joseph, Elizabeth K.*; Bogen, Oliver; Alessandri-Haber, Nicole; Levine, Jon D.

doi: 10.1016/j.pain.2007.01.027
Research papers
Buy
SDC

While protein kinase Cε has been shown to contribute to acute and chronic mechanical hyperalgesia, its upstream signaling pathway has received little attention. Since phospholipase C can signal to PKCε and has been implicated in nociceptor sensitization, we tested if it is upstream of PKCε in mechanisms underlying primary mechanical hyperalgesia. In the rat, the PKCε-dependent mechanical hyperalgesia and hyperalgesic priming (i.e., a form of chronic latent enhanced hyperalgesia) induced by carrageenan were attenuated by a non-selective PLC inhibitor U-73122. A lipid mediator of PLC signaling, l-α-lysophosphatidylcholine produced dose-dependent mechanical hyperalgesia and hyperalgesic priming, which was attenuated by EAVSLKPT, a selective PKCε inhibitor. However, U-73122 did not attenuate hyperalgesia induced by ψεRACK, a selective PKCε activator. Antisense to PLC-β3 isoform, which was found in small-diameter dorsal root ganglion neurons, also attenuated carrageenan-induced acute and chronic-latent hyperalgesia. These studies support the suggestion that PLC-β3 is an important upstream signaling molecule for PKCε-mediated acute and chronic inflammatory pain.

Department of Oral and Maxillofacial Surgery and Division of Neuroscience, University of California at San Francisco, 521 Parnassus Avenue, Box #0440/C522, San Francisco, CA 94143-0440, USA

*Corresponding author. Tel.: +1 415 476 4902; fax: +1 415 476 6305.

E-mail: Elizabeth.Joseph@ucsf.edu

Submitted September 1, 2006; received in revised form November 21, 2006; accepted January 29, 2007.

© 2007 Lippincott Williams & Wilkins, Inc.
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website