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Controlled study links pain-related genes to alcoholism

Researchers at Purdue University and Indiana University have identified a group of genes related to neural plasticity as well as physical and mental pain as an important driver of alcoholism.

“Numerous genes in the genome have been implicated with alcoholism. Everybody has their favorite gene, but absolute data and proof is hard to come by,” said Purdue University’s William Muir, professor emeritus of animal sciences. “We have strong statistical evidence that the same results occurred across six diversely selected genetic lines.”

The findings stem from special lineages of rats bred specifically for their drinking preferences at IU’s Indiana Alcohol Research Center. Studies of twins reared apart have long hinted that alcoholism, which affects an estimated 15 million Americans, includes a genetic component.

Muir and three co-authors from the Indiana University School of Medicine published the results in the journal Alcohol. The study involved statistically sorting through about 3 billion DNA base pairs containing nearly 30,000 genes, in 70 individual animals within six genetic lines bidirectionally selected over multiple generations for drinking preference to identify the handful that were responsible for drinking behaviors. 

Thanks to their experimental design, the researchers could identify population differences based on drinking behaviors rather than chance genetic differences or other environmental influences. The genes that mediate pain sensation act in concert with two other groups of neural channel and neural excitation genes which perform neural communication functions, the team found.

“The function of these three groups of genes is important for neuroadaptation and neuroplasticity, meaning that they can change brain communications,” said co-author Feng Zhou, professor emeritus of anatomy and cell biology at IU’s School of Medicine. 

The study’s findings all pointed to the same conclusion: The drinking desire lies in the brain. 

“The brain must be modified over the drinking period. That kind of modification is similar to drug abuse,” Zhou said. “It’s genetically prone neural plasticity or neural adaptation to a certain level that makes drinking more pleasurable, more tolerable. Or on the pain side, pain relief.” 

The alleviation of pain appears to be one motivation to drink and continue to drink, Muir noted. “Knowing that as a driver, it’s possible that early counseling can produce drinking avoidance,” he said. “It is hoped that the new findings one day lead to the possibility of genetic testing for tendency and prevention.”

If the genetic causes are known, developing more effective drugs to help address drinking problems might also become possible.

“One future direction is how these animal findings would translate to humans,” Zhou said. If verified, “Then treatment or prevention can be more focused.”

The National Institutes of Health supported this research. Additional study co-authors are Chiao-Ling Lo and Richard Bell, both of the IU School of Medicine.

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