An innovative study based on the behavior of a microscopic worm offers a new understanding of genetics at work when using drugs that can cause dependence.
A team at the Scripps Research Institute in Florida has discovered a biological system that controls how cells behave in the face of opioid drug exposure. Their results were published in the journal Science.
This unexpected discovery will allow the emergence of new ideas to improve the safety of these pain medications, considered the most effective but also the most addictive.
Microscopic and sequencing of the genome
For this study, the research team used a microscopic living organism in the soil, the nematode worm. These worms had been modified via the addition of a cell surface receptor, the opioid mu receptor (ROM) - reacting to the presence of pain-relieving drugs, such as morphine or fentanyl.
After exposure to these drugs, the researchers selected the worms that showed an abnormal response and subjected them to genome sequencing to find the genes responsible.
The study showed the role of the FRPR-13 receptor, present in all animals, and known as GPR139 in mammals. It is defined as a receptor coupled to the G protein but its physiological role is still poorly understood.
Additional tests in mice showed that GPR139 is expressed in the same neurons as ROM and against the effects of opioids in the neuronal firing.
"We are only at the beginning" of the response to the opioid crisis
When the researchers artificially activated the GPR139 receptor, the opioid-dependent mice stopped using them. Conversely, the genetic elimination of GPR139 increased the anti-pain effects of opioids. Mice lacking GPR139 also showed very little withdrawal symptoms following chronic opioid exposure.
"A study like this proves that even though we think we know all there is to know about the opioid crisis, we are only at the beginning," concludes Kirill Martemyanov, lead author of the study.
According to the National Institute on Drug Abuse, about 130 people a day die from an overdose of opioids in the United States. In addition, 5% of people taking opioids on prescription eventually switch to heroin use.
In France, since 2006, the number of deaths related to opioid use has increased by 146% between 2000 and 2015, with at least 4 deaths per week.