Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.

摘要: A major dose-limiting side effect of human immunodeficiency virus/acquired syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this HIV/AIDS treatment. Alcohol abuse, which alone produces one most important co-morbid risk factors for neuropathy in patients with HIV/AIDS. Despite prevalence problem and serious impact on quality life continued therapy patients, mechanisms alcohol abuse exacerbates highly active antiretroviral (HAART)-induced neuropathic pain has not been demonstrated. In study, performed rats, we investigated cellular mechanism consumed impacts antiretroviral-induced pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) was mitochondrial-dependent PKCe-independent, alcohol-induced PKCe-dependent mitochondrial-independent. At low doses, ddC (5 (6.5% ethanol diet 1 week), do affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia but PKCe-independent. These experiments, provide first model studying co-morbidity support clinical impression that consumption enhances evidence role underlying interaction.