A team of researchers at the University of California, San Diego (USA) has developed a gene silencing approach that provides mice with a higher pain tolerance threshold while reducing their sensitivity to pain for prolonged periods of time. weather. In the future, this new medical approach could represent a serious, safe and non-addictive alternative to treating chronic pain, for which opioids are currently prescribed for humans.
Genetic approach to treating pain
Taking oxycodone can ease pain, but it causes a number of other unwanted consequences in the brain, such as fueling addictions and suppressing breathing. Now, this study is presented as an approach that could prevent or reverse pain signaling without side effects; a sensation that occurs when the nerves that branch through our body reach the spinal cord to transmit messages to the brain. And these messages can persist even after the initial injury has healed, causing what we know as chronic pain.
” What we have now does not work. There is a desperate need for treatment that is effective, long-lasting and non-addictive,” clarifies Ana Moreno, leader of the work published in the journal Science Translational Medicine .
How exactly does it work?
The idea for such a treatment came when Moreno was a student in the laboratory of UC San Diego bioengineering professor Prashant Mali. Mali had been investigating the possibility of applying CRISPR-based gene therapy approaches to rare and common human diseases. Moreno’s project focused on exploring possible therapeutic avenues. He found that a genetic mutation made humans feel pain-free. This mutation inactivates a protein in neurons that transmit pain in the spinal cord, called NaV1.7. “By targeting this gene, we could alter the pain phenotype,” the expert thought.
The new method has worked successfully in mice. The experiments showed that it was possible to interfere with a gene that controls the sensation of physical pain, significantly reducing discomfort in the mice that had received chemotherapy. Gene therapy is thus based on turning off part of the system that transmits signals to the brain. Thus, this approach does not alter the DNA sequence itself and is also theoretically reversible , says Rajes Khanna, a neuroscientist who studies pain mechanisms and possible treatments at the University of Arizona. “I think this study will be our benchmark.”
In general, the treated animals had a lower sensitivity to pain, with lasting effects seen up to 44 weeks later in animals that had been subjected to forms of inflammatory pain.
If the results can be translated into humans and the treatment is shown to be safe, it could provide an alternative to opioids for the millions of people who are routinely in pain every day or undergo treatments that cause significant pain for long periods of time.
Referencia: Ana M. Moreno, Fernando Alemán, Glaucilene F. Catroli, Matthew Hunt, Michael Hu, Amir Dailamy, Andrew Pla, Sarah A. Woller, Nathan Palmer, Udit Parekh, Daniella McDonald, Amanda J. Roberts, Vanessa Goodwill, Ian Dryden, Robert F. Hevner, Lauriane Delay, Gilson Gonçalves dos Santos, Tony L. Yaksh, Prashant Mali. Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice. Science Translational Medicine, 2021; 13 (584): eaay9056 DOI: 10.1126/scitranslmed.aay9056
