Animal models of alcoholic neuropathy: Morphologic, electrophysiologic, and biochemical findings

Bosch, E. Peter; Pelham, Russell W.; Rasool, C. G.; Chatterjee, Anadi N.; Lash, Robert W.; Brown, Laura T.; Munsat, Theodore L.; Bradley, Walter G.

doi:10.1002/mus.880020208

Cited by 74 publications

(37 citation statements)

References 43 publications

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“…Rats chronically fed ethanol exhibited mechanical and thermal hyperalgesia and tactile allodynia, all of which are symptoms frequently occurring in patients with painful peripheral neuropathy (Scadding, 1992). This model is highly relevant to painful alcoholic neuropathy in humans because the blood alcohol level that results in neuropathic changes is similar (Bosch et al, 1979;. Also, the fact that hyperalgesia is stable for weeks renders this model very useful for study of underlying mechanism.…”

Section: Discussionmentioning

confidence: 95%

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

et al. 2000

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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 PKC⑀ inhibitors injected at the site of nociceptive testing. Western immunoblot analysis indicated a higher level of PKC⑀ in dorsal root ganglia from alcohol-fed rats, supporting a role for enhanced PKC⑀ secondmessenger signaling in nociceptors contributing to alcohol-induced hyperalgesia.Key words: protein kinase C ⑀; alcoholic peripheral neuropathy; pain; hyperalgesia; allodynia; primary afferent nociceptor Ethanol consumption is the most common cause of peripheral nervous system, as well as CNS, neurotoxicity. Ethanol is thought to exert a direct neurotoxic action on the peripheral nervous system, resulting in a neuropathy that mostly involves smalldiameter fibers (Diamond and Messing, 1994;Monforte et al., 1995;Kielhorn, 1996;Ortiz-Plata et al., 1998;Tredici et al., 1999). The peripheral neuropathy is a potentially incapacitating complication of chronic consumption of ethanol, characterized by pain and dysesthesias, primarily in the lower extremities, and is poorly relieved by available therapies (Ratcliff, 1979;Monforte et al., 1995;Ortiz-Plata et al., 1998).Whereas enhanced nociception and primary afferent nociceptor hypersensitivity have been demonstrated in animal models of other neuropathic pain states, such as those induced by diabetes (Ahlgren and Levine, 1994), chemotherapy (Tanner et al., 1998; Authier et al., 1999), or trauma (Bennett andXie, 1988;Campbell et al., 1988;Seltzer et al., 1990;Xie and Xiao, 1990;Kim and Chung, 1992;Kim et al., 1993;Sheen and Chung, 1993;Yoon et al., 1996;Pedersen and Kehlet, 1998;Zahn and Brennan, 1999), an animal model for alcohol-induced neuropathy does not exist, nor has it even been demonstrated that primary afferent nociceptor function is altered by chronic exposure to alcohol.In animal models of other painful peripheral neuropathies, enhanced nociception involves alterations in intracellular signaling. Specifically, protein kinase C (PKC) (Ahlgren and Levine, 1994) [particularly the epsilon (⑀) isoform (Gerstin et al., 1998; Khasar et al., 1999] and protein kinase A (PKA) (Ahlgren and Levine, 1994) signaling pathways have been implicated in enhancing nociceptor function. Because alcohol has been shown to activate PKC and PKA (Coe et al., 1...

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Section: Discussionmentioning

confidence: 95%

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

et al. 2000

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“…In addition to thiamine deficiency, recent studies indicate a direct neurotoxic effect of ethanol or its metabolites. Axonal degeneration has been documented in rats receiving ethanol while maintaining normal thiamine status [30]. Human studies have also suggested a direct toxic effect, since a dose-dependent relationship has been observed between severity of neuropathy and total lifetime dose of ethanol [29,31].…”

Section: Pathogenesismentioning

confidence: 98%

Alcoholic neuropathy

Koike

Sobue

2006

Current Opinion in Neurology

108

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“…Although neuropathy is frequently seen in chronic alcoholics, there have been few reports on its prevalence (9-50%) (Bolton, 1987;Charness et al, 1989;Victor, 1994;Monforte et al, 1995;Pessione et al, 1995). Alcohol-related neuropathy is also associated with several risk factors, such as malnutrition, thiamine deficiency, direct toxicity of alcohol and a family history of alcoholism (Victor, 1975;Bosch et al, 1979;Claus et al, 1985;Monforte et al, 1995;Pessione et al, 1995), but it is not clear which of these plays a primary role in inducing neuropathy (Estruch et al, 1993;Palliyath and Schwartz, 1993). While the hyperalgesia produced by neuropathy has been demonstrated in animal models of other neuropathic pain states, there are few animal models of alcoholic neuropathy.…”

Section: Introductionmentioning

confidence: 99%

Changes in function of NMDA receptor NR2B subunit in spinal cord of rats with neuropathy following chronic ethanol consumption

et al. 2007

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Animal models of alcoholic neuropathy: Morphologic, electrophysiologic, and biochemical findings

Cited by 74 publications

References 43 publications

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

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

Alcoholic neuropathy

Changes in function of NMDA receptor NR2B subunit in spinal cord of rats with neuropathy following chronic ethanol consumption

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