Electrophysiological and Behavioral Changes by Phosphodiesterase 4 Inhibitor in a Rat Model of Alcoholic Neuropathy

OBJECTIVE: Alcoholic neuropathy is characterized by allodynia (a discomfort evoked by normally innocuous stimuli), hyperalgesia (an exaggerated pain in response to painful stimuli) and spontaneous burning pain. The aim of the present study is to investigate the effect of rolipram, a phosphodiesterase 4 inhibitor, against alcohol-induced neuropathy in rats. METHODS: Allodynia was induced by administering 35% v/v ethanol (10 g/kg; oral gavage) to Spraue-Dawley rats for 8 weeks. Rolipram and saline (vehicle) were administered intraperitoneally. Mechanical allodynia was measured by using von Frey filaments. Somatosensory evoked potential (SEP) was proposed as complementary measure to assess the integrity of nerve pathway. RESULTS: The ethanol-induced mechanical allodynia began to manifest from 3 week, and then peaked within 1 week. Beginning from 3 week, latency significantly started to increased in control group. In rolipram treated rats, the shorter latency was sustained until 8 weeks (p<0.05). The mechanical allodynia, which began to manifest on the 3 weeks, intraperitoneal injections of rolipram sustained statistical difference until 8 weeks, the final week of the study (p<0.05). CONCLUSION: This study suggests that rolipram might alleviate mechanical allodynia induced by alcohol in rats, which clearly has clinical implication.

Alcohol-Related Neurologic Disorders: Ten Years of Experiences

Alcohol-related disorders are among the most costly health problems worldwide. Ingested alcohol is mainly metabolized by an oxidative pathway in the liver. Alcohol and its metabolic products (e.g., acetaldehyde and reactive oxygen species) have toxic effects on multiple organs, especially the nervous system. The diverse mechanisms of alcohol-related neurologic disorders include the direct toxic effects of alcohol, the alcohol withdrawal effect, nutritional deficiency secondary to alcoholism, and abnormalities of serum electrolytes and osmolality. We analyzed 156 cases of alcoholrelated neurologic disorders among admitted patients that had been referred in Korea during the previous 10 years. The duration of alcohol consumption ranged from 0.5 to 47 years (mean=17.8 years) and the mean amount of alcohol intake per day was 245.5 g. The 156 patients had the following diseases: Wernicke's encephalopathy (n=81, 51.9%), peripheral neuropathy (n=68, 43.6%), delirium tremens (n=59, 37.8%), Rum fit (n=31, 19.9%), pellagra encephalopathy (n=29, 18.6%), Korsakoff's psychosis (n=22, 14.2%), cerebellar atrophy (n=11, 7.0%), and alcoholic myopathy (n=6, 3.8%). We report on these cases and review the literature on alcohol-related neurologic disorders.