PLC-β3 signals upstream of PKCε in acute and chronic inflammatory hyperalgesiaJoseph, Elizabeth K.*; Bogen, Oliver; Alessandri-Haber, Nicole; Levine, Jon D.PAIN: November 2007 - Volume 132 - Issue 1 - p 67–73 doi: 10.1016/j.pain.2007.01.027 Research papers Buy SDC Abstract Author InformationAuthors Article MetricsMetrics 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.