New research reveals how both alcohol consumption and withdrawal have the potential to result in hypersensitivity and increased chronic pain
Two different molecular mechanisms may be the reason chronic alcohol consumption results in an increased sensitivity to pain, according to research published in the British Journal of Pharmacology.
Scientists at Scripps Research revealed the conclusion that one molecular mechanism is driven by alcohol intake and the other by alcohol withdrawal through their research on the complex links between alcohol and pain.
“Our goal is to unveil new potential molecular targets that can be used to distinguish these types of pain and potentially be used in the future for the development of therapies,” commented co-senior author Nicoletta Galeotti, PhD, associate professor of preclinical pharmacology at the University of Florence.
“Our goal is to unveil new potential molecular targets that can be used to distinguish these types of pain”
Alcohol use disorder and human health
Alcohol use disorder (AUD) affects 29.5 million people in the U.S according to a 2019 survey and encompasses conditions such as alcohol abuse, alcohol dependence and alcohol addiction.
Prolonged AUD can trigger numerous chronic diseases, including heart disease, stroke, liver disease and some cancers. Along with these long-term impacts, more than half of people with AUD experience some type of persistent pain.
Chronic pain and its relationship with chronic alcohol consumption
“There is an urgent need to better understand the two-way street between chronic pain and alcohol dependence,” says senior author Marisa Roberto, PhD, the Schimmel Family Chair of Molecular Medicine, and a professor of neuroscience at Scripps Research.
“Pain is both a widespread symptom in patients suffering from alcohol dependence, as well as a reason why people are driven to drink again.”
Along with revealing new connections, the research has also suggested potential new drug targets for treating alcohol-associated chronic pain and hypersensitivity, which has the potential to change lives.
A catch-22: Alcohol consumption and withdrawal
Prolonged alcohol consumption can result in alcoholic neuropathy, which is nerve damage that causes chronic pain and other symptoms. Along with this, studies have also found that AUD is associated with changes in how the brain processes pain signals, as well as changes to how immune system activation occurs.
Many who experience this pain turn to increased alcohol consumption as a form of relief but this, in turn, can make everything worse.
During withdrawal, those with AUD can experience allodynia, a harmless stimulus that is perceived as painful
During withdrawal, those with AUD can experience allodynia, a harmless stimulus that is perceived as painful.
Animal testing: Allodynia, AUD, and alcohol withdrawal
Author Marisa Roberto and her colleagues were interested in learning the underlying causes of the types of alcohol-related pain. In their most recent study, they compared three groups of adult mice: animals that were dependent on alcohol (excessive drinkers), animals that had limited access to alcohol and were not considered dependent (moderate drinkers), and those that had never been given alcohol.
In dependent mice, allodynia developed during alcohol withdrawal, and subsequent alcohol access significantly decreased pain sensitivity.
Separately, about half of the mice that were not dependent on alcohol 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 then measured levels of inflammatory proteins in the animals, they discovered that while inflammation pathways were elevated in both dependent and non-dependent animals, specific molecules were only increased in dependent mice.
This indicated that different molecular mechanisms might drive the two types of pain. It also suggested which inflammatory proteins might be useful as drug targets to combat alcohol-related chronic pain.
“These two types of pain vary greatly, which is why it is important to be able to distinguish between them and develop different ways to treat each type,” says first author Vittoria Borgonetti, PhD, a postdoctoral associate at Scripps Research.
