Researchers at Scripps Research have discovered that chronic alcohol consumption can increase disease sensitivity through two different molecular mechanisms: one related to alcohol consumption and the other to withdrawal. of wine. This finding, published in British Journal of Pharmacologysheds light on the complex relationship between alcohol and disease.
Researchers seek to better understand the relationship between chronic disease and alcohol use disorders. They want to investigate the underlying causes of various alcohol-related diseases, such as alcoholic neuropathy and allodynia, and how they develop at the level of the spinal cord. The researchers aimed to examine the role of microglia, immune cells in the central nervous system, in the development of alcohol-induced chronic allodynia and neuropathy.
Alcoholic neuropathy refers to nerve damage caused by long-term excessive alcohol consumption. It is a type of peripheral neuropathy that affects the peripheral nerves, which are responsible for sending signals between the brain, spinal cord, and the rest of the body.
Chronic alcohol use can lead to nutritional deficiencies and toxins that directly damage the nerves, resulting in symptoms such as pain, tingling, numbness, muscle weakness, and problems with coordination and balance. Alcoholic neuropathy usually affects the extremities, such as the hands and feet, and can have a significant impact on a person’s quality of life.
Allodynia, on the other hand, is a condition characterized by the perception of pain from normally non-painful stimuli. In other words, it is the experience of pain in response to a stimulus that is not usually painful, such as a gentle touch or gentle pressure.
“More than half of patients suffering from alcohol-related disorders develop pain. Chronic pain is considered the main factor contributing to the maintenance of alcohol use disorder because people drink more to reduce it. For this reason, we are focusing on the molecular mechanism that highlights the relationship between the disease and alcohol consumption,” said study authors Marisa Roberto and Vittoria Borgonetti of Scripps Research Institute.
To conduct their study, the researchers used adult rats divided into three groups: alcohol-dependent rats (heavy drinkers), rats with limited access to alcohol (moderate drinkers ), and rats that had not been given alcohol. They used a chronic intermittent ethanol vapor paradigm to induce alcohol dependence in rats. This paradigm involves cycles of alcohol exposure and withdrawal, mimicking the development of alcohol dependence in humans. Rats were subjected to various tests to measure mechanical allodynia and neuropathic pain.
The researchers found that alcohol-dependent mice showed higher levels of mechanical allodynia compared to both moderate drinkers and alcohol-naive mice. They also observed changes in protein levels in the spinal cord and sciatic nerve of alcohol-dependent mice, particularly in microglial cells. These changes suggested the activation of microglia and the involvement of inflammatory processes in the development of alcohol-induced disease.
The researchers also discovered that there were two different types of disease conditions that occurred as a result of alcohol use. In alcohol-dependent mice, they experienced a condition called allodynia, which means they became more sensitive to pain during alcohol withdrawal. However, when these dependent rats were given access to alcohol again, their pain sensitivity was significantly reduced.
On the other hand, among the non-alcohol-dependent rats, about half of them also showed increased sensitivity to pain (hyperalgesia) during alcohol withdrawal. This is similar to what the dependent rats experienced. However, the main difference was that in these non-dependent rats, the increased pain sensitivity did not disappear when they were re-exposed to alcohol. The pain persisted even after re-exposure to alcohol.
“The study highlights two different conditions of alcohol consumption: heavy drinkers who develop alcohol dependence, and moderate drinkers, those who make daily drink alcohol recreationally. These two different conditions have shown different types of pain: withdrawal hyperalgesia in heavy drinkers who develop dependence and alcohol neuropathy in 50 percent of moderate drinkers,” said Roberto and Borgonetti in PsyPost.
“Hyperalgesia is a transient pain condition, closely related to alcohol withdrawal and part of negative emotional states, which often prompts the patient to drink more alcohol. Alcoholic neuropathy is a persistent and almost irreversible damage of the somatosensory system, associated with drinking alcohol in recreational amounts and not associated with addiction; therefore, it is not resolved by drinking additional alcoholic beverages, which, on the contrary, makes it stand out.”
Both of these disease conditions involve severe activation of microglia in the spinal cord tissue of mice. Microglia are known to play a role in the body’s response to injury or inflammation.
Interestingly, the two disease conditions seem to involve different pathways within microglia. In dependent mice with abstinence-related hypersensitivity, we observed an increase in the expression of a protein called IL-6 and the activation of another protein called ERK44/42. However, these changes were not observed in rats with alcohol-induced neuropathic pain.
These findings contribute to a better understanding of the relationship between chronic disease and alcohol use disorder, emphasizing the complex interactions between alcohol consumption, disease , and of the immune system.
“It is important to understand the molecular mechanisms that underlie the two-way relationship between chronic disease and alcohol dependence,” said Roberto and Borgonetti. “In fact, the two forms of the disease share strong inflammation, but what we observed was that specific inflammatory molecules were increased only in conditions of withdrawal hyperalgesia and not in neuropathy. This suggests that the two forms of the disease that it may be driven by different molecular mechanisms.
The studying, “Chronic alcohol-induced mechanical allodynia by promoting neuroinflammation: A mouse model of alcohol-induced neuropathic pain.“, was written by Vittoria Borgonetti, Amanda J. Roberts, Michal Bajo, Nicoletta Galeotti, and Marisa Roberto.