PLC-beta 3 signals upstream of PKC epsilon in acute and chronic inflammatory hyperalgesia.
While protein kinase C epsilon 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 PKC epsilon and has been implicated in nociceptor sensitization, we tested if it is upstream of PKC epsilon in mechanisms underlying primary mechanical hyperalgesia. In the rat, the PKC epsilon-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-alpha-lysophosphatidylcholine produced dose-dependent mechanical hyperalgesia and hyperalgesic priming, which was attenuated by EAVSLKPT, a selective PKC epsilon inhibitor. However, U-73122 did not attenuate hyperalgesia induced by psi epsilon RACK, a selective PKC epsilon activator. Antisense to PLC-beta 3 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-beta 3 is an important upstream signaling molecule for PKC epsilon-mediated acute and chronic inflammatory pain.
Joseph
Elizabeth K
EK
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. Elizabeth.Joseph@ucsf.edu
Bogen
Oliver
O
Alessandri-Haber
Nicole
N
Levine
Jon D
JD
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D006930:Hyperalgesia / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D054799:Phospholipase C beta; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014110:Touch; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D051744:Protein Kinase C-epsilon; D010738:Type C Phospholipases; D054799:Phospholipase C beta