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The Journal of Neuroscience, June 15, 2000, 20(12):4680-4685

Chronic Hypersensitivity For Inflammatory Nociceptor Sensitization Mediated by the  Isozyme of Protein Kinase C

K. O. Aley¹, Robert O. Messing², Daria Mochly-Rosen³, and Jon D. Levine¹

¹ National Institutes of Health Pain Center, University of California, San Francisco, San Francisco, California 94143-0440, ² Ernest Gallo Clinic and Research Center, University of California, Emeryville, California 94608, and ³ Molecular Pharmacology, Stanford University, Stanford, California 94305

We have identified a mechanism, mediated by the  isozyme of protein kinase C (PKC) in peripheral neurons, which may have a role in chronic inflammatory pain. Acute inflammation, produced by carrageenan injection in the rat hindpaw, produced mechanical hyperalgesia that resolved by 72 hr. However, for up to 3 weeks after carrageenan, injection of the inflammatory mediators prostaglandin E₂ or 5-hydroxytryptamine or of an adenosine A₂ agonist into the same site induced a markedly prolonged hyperalgesia (>24 hr compared with 5 hr or less in control rats not pretreated with carrageenan). A nonselective inhibitor of several PKC isozymes and a selective PKC inhibitor antagonized this prolonged hyperalgesic response equally. Acute carrageenan hyperalgesia could be inhibited by PKA or PKG antagonists. However, these antagonists did not inhibit development of the hypersensitivity to inflammatory mediators. Our findings indicate that different second messenger pathways underlie acute and prolonged inflammatory pain.

Key words: carrageenan; chronic pain; inflammation; prostaglandin E2; protein kinase C; second messenger

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20124680-06$05.00/0

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