Key role for the epsilon isoform of protein kinase C in painful alcoholic neuropathy in the rat.
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 PKCepsilon inhibitors injected at the site of nociceptive testing. Western immunoblot analysis indicated a higher level of PKCepsilon in dorsal root ganglia from alcohol-fed rats, supporting a role for enhanced PKCepsilon second-messenger signaling in nociceptors contributing to alcohol-induced hyperalgesia.
Dina
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OA
Departments of Medicine and Oral and Maxillofacial Surgery, Division of Neuroscience and Biomedical Sciences Program, National Institutes of Health Pain Center (UCSF), University of California at San Francisco, San Francisco, California 94143-0440, USA.
Barletta
J
J
Chen
X
X
Mutero
A
A
Martin
A
A
Messing
R O
RO
Levine
J D
JD
D000200:Action Potentials; D020269:Alcoholic Neuropathy / Q000139:chemically induced / Q000201:enzymology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D002149:Energy Intake / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D007527:Isoenzymes; D000431:Ethanol; C497257:Prkce protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon