Key Role for the Epsilon Isoform of Protein Kinase C in Painful Alcoholic Neuropathy in the Rat

O. Dina,Justine Barletta,Xiaojie Chen,A. Mutero,Annick Martin,R. Messing,J. Levine

Published 2000 in Journal of Neuroscience

ABSTRACT

Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliably successful therapy, attributable to, in great part, a lack of understanding of the underlying mechanisms. We tested the hypothesis that neuropathic pain associated with chronic alcohol consumption is a result of abnormal peripheral nociceptor function. In rats maintained on a diet to simulate chronic alcohol consumption in humans, mechanical hyperalgesia was present by the fourth week and maximal at 10 weeks. Thermal hyperalgesia and mechanical allodynia were also present. Mechanical threshold of C-fibers in ethanol fed rats was lowered, and the number of action potentials during sustained stimulation increased. The hyperalgesia was acutely attenuated by intradermal injection of nonselective protein kinase C (PKC) or selective PKCε inhibitors injected at the site of nociceptive testing. Western immunoblot analysis indicated a higher level of PKCε in dorsal root ganglia from alcohol-fed rats, supporting a role for enhanced PKCε second-messenger signaling in nociceptors contributing to alcohol-induced hyperalgesia.

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