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New painkiller could tackle pain, without risk of addiction

Stanford researchers uncover painkiller and pain pathway of particular interest to millions of Asians with alcohol-metabolizing enzyme mutation.

painkillersThose suffering from chronic pain, take note: A new pain-reliever may soon be on the scene that lacks the “high” of opioids and the cardiac-risk of non-steroidal anti-inflammatory (NSAIDs) drugs such as aspirin. The compound reduced inflammatory pain in mice, according to research by a team of Stanford scientists led by Daria Mochly-Rosen, PhD, a professor of chemical and systems biology.

Mochly-Rosen discovered the compound, called Alda-1, more than five years ago while searching for the reason moderate alcohol use can decrease the severity of heart attacks. She found an enzyme, called aldehyde dehydrogenase 2, that breaks down a family of alcohol byproducts, called aldehydes. Aldehydes also cause pain in mice and Alda-1 relieves the pain, Mochly-Rosen said.

“I’m not a pain expert,” Mochly-Rosen says in our release on the Science Translational Medicine paper. “We hit this enzyme for a completely different reason. Hopefully this will help people who have pain.”

Alda-1 — coincidentally, Alda is also the name of Mochly-Rosen’s 87-year-old mother — works by knocking aldehyde dehydrogenase 2 into high gear. Say goodbye to the aldehydes, and goodbye to the pain.

Mochly-Rosen’s discovery of the link between pain and Alda-1 is a big deal for many reasons, including the suffering of thousands addicted to opioids such as Oxycontin. It’s also particularly meaningful for the millions in the Han Chinese ethnic group who suffer from alcohol flush.  They have a mutation in aldehyde hydrogenate 2, which makes it uncomfortable to drink alcohol and causes sufferers to turn red.

The inflammation is caused by the build-up of aldehydes, which are byproducts of alcohol. Alcohol-flush syndrome, as it’s sometimes called, has been recognized for decades.

The researchers created a mouse with a mutation akin to the enzyme mutation in humans. When they injected aldehydes into the mice, the mice with the mutation felt more pain than the other mice. And Alda-1 also relieved their pain.

Dribbles of evidence suggest some Asians are more sensitive to pain. Now, Mochly-Rosen and her team plan to investigate if the susceptibility stems from the enzyme mutation.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Another big step toward building a better aspirin tablet, Blocking addiction risks of morphine without reducing its pain-killing effects, Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers, and Stanford’s Sean Mackey discusses recent advances in pain research and treatment
Photo by Michelle Tribe/Wikimedia Commons

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