Chronic alcohol use can make people more sensitive to pain through two different molecular mechanisms: one driven by alcohol intake and one driven by alcohol withdrawal. That’s a new finding from Scripps Research scientists about the complex links between alcohol and pain.
The research, published in the british journal of pharmacology on April 12, 2023, also suggests potential new drug targets to treat alcohol-associated chronic pain and hypersensitivity.
“There is an urgent need to better understand the two-way street between chronic pain and alcohol dependence,” says lead author Marisa Roberto, PhD, Chair of Schimmel Family Molecular Medicine and professor of neuroscience at Scripps Research. “Pain is a widespread symptom in patients suffering from alcohol dependence, as well as a reason people are forced to drink again.”
Alcohol use disorder (AUD), which encompasses conditions commonly called alcohol abuse, alcohol dependence, and alcohol addiction, affects 29.5 million people in the US according to the National Survey on Drug Use and health of 2021. Over time, AUD can trigger the development of numerous chronic diseases, including heart disease, stroke, liver disease, and some types of cancer.
Among the many long-term impacts of alcohol use is pain: More than half of people with AUD experience persistent pain of some kind. This includes alcoholic neuropathy, which is nerve damage that causes chronic pain and other symptoms. Studies have also found that AUD is associated with changes in the way the brain processes pain signals, as well as changes in the way activation of the immune system occurs. In turn, this pain can lead to increased alcohol consumption. Additionally, during withdrawal, people with AUD may experience allodynia, in which a harmless stimulus is perceived as painful.
Roberto and his colleagues were interested in learning about the underlying causes of these different types of alcohol-related pain. In the new study, they compared three groups of adult mice: animals that were dependent on alcohol (heavy drinkers), animals that had limited access to alcohol and did not consider themselves dependent (moderate drinkers), and those that had never been given alcohol.
In dependent mice, allodynia developed during alcohol withdrawal, and subsequent access to alcohol significantly decreased pain sensitivity. Separately, about half of the non-alcohol-dependent mice also showed signs of increased pain sensitivity during alcohol withdrawal but, unlike the dependent mice, this neuropathy was not reversed by re-exposure to alcohol.
When Roberto’s group measured the levels of inflammatory proteins in the animals, they found that while the inflammatory pathways were elevated in both the dependent and non-dependent animals, specific molecules were only increased in the dependent mice. This indicates that different molecular mechanisms may drive the two types of pain. It also suggests which inflammatory proteins may be useful as drug targets to combat alcohol-related pain.
“These two types of pain vary greatly, so it’s important to be able to tell them apart and develop different ways to treat each type,” says first author Vittoria Borgonetti, PhD, a postdoctoral associate at Scripps Research.
Roberto’s group continues to study how these molecules could be used to diagnose or treat alcohol-related chronic pain conditions.
“Our goal is to reveal potential new molecular targets that can be used to distinguish these types of pain and potentially be used in the future for the development of therapies,” says co-lead author Nicoletta Galeotti, PhD, an associate professor of preclinical pharmacology at the University of Florence. .
In addition to Roberto, authors of the study, “Chronic Alcohol-Induced Mechanical Allodynia by Promoting Neuroinflammation: A Predictive Model of Alcoholic Neuropathy in Mouse,” include Amanda Roberts, Michal Bajo, and Vittoria Borgonetti of Scripps Research; and Nicoletta Galeotti from the University of Florence.
This work was supported by funds from the National Institutes of Health (Integrative Neuroscience Initiative on Alcoholism Consortium AA013498, AA027700, AA021491, AA017447, AA006420, and AA029841), the Schimmel Family President, the Pearson Center for Research on Alcoholism and Addiction, and the Scripps Research Institute Animal Models Core Facility.
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