Reactive aldehydes: an initial path to develop precision medicine for pain control.

With the risks of opioid addiction, abuse, and overdose, there is a need to identify new molecular targets contributing to pain sensation in order to develop directed treatments for pain. One mechanism to treat pain is to target reactive aldehydes either by limiting production or by increasing metabolism. In response to a recent editorial in the Annals of Translational Medicine (ATM), we discuss how reactive aldehyde production can trigger pain and how the enzyme mitochondrial aldehyde dehydrogenase 2 (ALDH2) regulates inflammatory pain by reactive aldehyde metabolism. We also comment about the possible clinical impact caused by the inefficiency of reactive aldehyde metabolism for the ~540 million people with an ALDH2*2 variant. Further, we discuss how developing therapeutics specifically targeting ALDH2 may lead to the development of a pathway to potentially create precision medicine for pain control.