title: Peripheral systems: neuropathy.
abstract: Long-term, excessive consumption of alcoholic beverages produces a peripheral neuropathy with symptoms of decreased superficial sensation, hyperalgesia, and weakness. Alcoholic neuropathy is characterized by axonal degeneration with reduced density of both small and large fibers and axonal sprouting. Electrophysiologic studies reveal a marked reduction in the amplitude of sensory potentials and moderate slowing of nerve conduction, mainly in the lower extremities. Dietary deficiency of vitamins, which are often associated with chronic alcoholism, can contribute to the pathogenesis. Recent studies using animal models have identified several mechanisms by which ethanol impacts peripheral nerve function. Ethanol can exert direct neurotoxic effects on peripheral nerves via its metabolite acetaldehyde and by enhancing oxidative stress. Ethanol activation of protein kinase Cε signaling in primary afferent nociceptors plays an important role in lowering nociceptive threshold. Further, ethanol causes cytoskeletal dysfunction and inhibits both anterograde and retrograde axonal transport. Alcoholic neuropathy is potentially reversible and treatments include abstinence from alcoholic beverages and consumption of a nutritionally balanced diet supplemented with B vitamins. However, response to these treatment strategies can be variable, which underscores the need for novel therapeutic strategies. In this review, we provide an overview of the clinical findings and insights on molecular mechanisms from animal models.
authors.affiliation: College of Pharmacy, University of Texas, Austin, TX, USA.
authors.forename: Rajani P
authors.initials: RP
authors.lastname: Maiya
authors.affiliation: College of Pharmacy, University of Texas, Austin, TX, USA. Electronic address: romessing@austin.utexas.edu.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D020269:Alcoholic Neuropathy / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D000437:Alcoholism / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D000818:Animals; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D013832:Thiamine Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology
keywords: acetaldehyde; alcohol use disorder; axonal transport; cytoskeleton; ethanol; folate; neuropathy; oxidative stress; pain; protein kinase C epsilon; thiamine