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The Convergent Neuroscience of Affective Pain and Substance Use Disorder

Introduction

A central feature of substance use disorder (SUD) is the emergence of negative affective or emotional states that influence the motivational properties of misused substances.1 Individual propensity to experience pain-related negative affect, for example, is hypothesized to be associated with the maintenance of both opioid use disorder (OUD) and alcohol use disorder (AUD). Chronic...

Alcoholic Myopathy: Pathophysiologic Mechanisms and Clinical Implications

Skeletal muscle dysfunction (i.e., myopathy) is common in patients with alcohol use disorder. However, few clinical studies have elucidated the significance, mechanisms, and therapeutic options of alcohol-related myopathy. Preclinical studies indicate that alcohol adversely affects both anabolic and catabolic pathways of muscle-mass maintenance and that an increased proinflammatory and oxidative...

Macrophages and Alcohol-Related Liver Inflammation

Alcoholic liver disease (ALD) is a complex disease that affects millions of people worldwide and eventually can lead to liver cirrhosis and liver cancer (i.e., hepatocellular carcinoma). Aside from the direct cytotoxic and the oxidative-stress–mediated effects that alcohol and its metabolite, acetaldehyde, exert on hepatocytes, alcohol ingestion activates both the innate and adaptive immune...

Neuroimmune Function and the Consequences of Alcohol Exposure

Induction of neuroimmune genes by binge drinking increases neuronal excitability and oxidative stress, contributing to the neurobiology of alcohol dependence and causing neurodegeneration. Ethanol exposure activates signaling pathways featuring high-mobility group box 1 and Toll-like receptor 4 (TLR4), resulting in induction of the transcription factor nuclear factor kappa-light-chain-enhancer of...

Alcohol Misuse and Kidney Injury: Epidemiological Evidence and Potential Mechanisms

Chronic alcohol consumption is a well-known risk factor for tissue injury. The link between alcohol use disorder (AUD) and kidney injury is intriguing but controversial, and the molecular mechanisms by which alcohol may damage the kidneys are poorly understood. Epidemiological studies attempting to link AUD and kidney disease are, to date, inconclusive, and there is little experimental evidence...

Alcohol's Unique Effects on Cognition in Women: A 2020 (Re)view to Envision Future Research and Treatment

Alcohol use and misuse is increasing among women. Although the prevalence of drinking remains higher in men than women, the gender gap is narrowing. This narrative review focuses on the cognitive sequelae of alcohol consumption in women. Studies of acute alcohol effects on cognition indicate that women typically perform worse than men on tasks requiring divided attention, memory, and decision...

Immune Function Genes, Genetics, and the Neurobiology of Addiction

The nervous system and the immune system interact closely to regulate the body’s immune responses, including inflammatory responses. Accordingly, the term “neuroimmune system” refers to the immune system and those components of the nervous system that help regulate immune responses and also encompasses the hormones and other signaling molecules that convey signals between the immune and nervous...

Epigenetic Targets for Reversing Immune Defects Caused by Alcohol Exposure

Extensive clinical and experimental data suggest that alcohol consumption has dose-dependent modulatory effects on the immune system that influence the two arms of the immune response (i.e., innate and adaptive immune responses). In many other organ systems, such as the brain and liver, alcohol consumption has been shown to alter factors that can modify gene expression without changing the DNA...

Dysregulation of microRNA Expression and Function Contributes to the Etiology of Fetal Alcohol Spectrum Disorders

MicroRNAs (miRNAs) are members of a vast, evolutionarily ancient, but poorly understood class of regulatory RNA molecules, termed non–protein-coding RNAs (ncRNAs). This means that in contrast to RNA molecules generated during gene expression (i.e., messenger RNA [mRNA] molecules), they are not used as templates for the synthesis of proteins. ncRNAs are encoded within the genomes of both eukaryotic...