Although morphine and aspirin are effective at dulling pain, they come with consequences. For instance, morphine can be addictive. And aspirin can cause gastrointestinal bleeding. Searching for painkillers without these side effects, a research team led by Daria Mochly-Rosen of Stanford University School of Medicine has hit upon one compound, called Alda-1, that might fit the bill (Sci. Transl. Med. 2014, DOI: 10.1126/scitranslmed.3009539). Alda-1 enhances the activity of aldehyde dehydrogenase-2, an enzyme whose job it is to break down potentially harmful aldehydes in the body into innocuous acids. The researchers genetically engineered mice to produce a defective version of the enzyme and then injected the rodents’ paws with inflammatory chemicals. Not only did the paws accumulate aldehydes such as 4-hydroxynonenal, but the mice also exhibited a lower tolerance to pain. When the team gave Alda-1 to these mice and to normal mice, both sets displayed an increased pain threshold. All the animals benefited from Alda-1, Mochly-Rosen says, because the compound fixes the aldehyde dehydrogenase-2 defect in the engineered mice and boosts the enzyme’s activity in normal mice. The team will next study whether Alda-1 is effective against types of pain other than acute inflammation.