More than half a billion people carry a genetic mutation that incapacitates the enzyme responsible for clearing alcohol from the body. The deficiency is responsible for an alcohol flush reaction, colloquially known as the “Asian glow” because the vast majority of carriers are descendants of the Han Chinese. Now research published last September in Science Translational Medicine suggests that the mutation might also compromise carriers' pain tolerance. The finding points to a new target for pharmaceutical pain relief and implies that drinking alcohol might exacerbate inflammatory conditions such as arthritis.
When people consume alcohol, the body breaks it down into several by-products, including chemicals called aldehydes. These compounds are noxious if they remain in the system too long, causing flushing, nausea, dizziness and other symptoms of the alcohol flush reaction. In most people, aldehydes are immediately broken down by the enzyme aldehyde dehydrogenase (ALDH2), but in those with the genetic mutation, the enzyme is incapacitated.
Researchers led by Daria Mochly-Rosen of Stanford University genetically modified some mice to carry the mutation seen in humans that disables ALDH2. When they injected those mice and normal mice in the paw with an inflammatory compound that turned it red and swollen, mice carrying the mutation showed increased sensitivity to a poke compared with those with functioning ALDH2. When the researchers treated all the rodents with a novel drug called Alda-1 that boosts ALDH2 activity, the pain symptoms were reduced regardless of whether they carried the gene mutation.
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The investigators were surprised to find aldehydes at the site of inflammation because the mice had not been exposed to alcohol. The discovery suggests that natural aldehydes produced by the body contribute significantly to pain and that they are kept in check by ALDH2.
What the research will mean for people remains to be seen. Mochly-Rosen next hopes to determine whether people with the mutation experience pain differently than those without it. Anecdotally, some descendants of the Han Chinese seem to have a lower pain threshold, but so far that has been blamed on cultural factors. If ALDH2 does affect pain in humans and if Alda-1 activates the enzyme in humans as it does in rodents, then the agent could potentially boost aldehyde metabolism and lower pain in people with or without the mutation.
A new pharmaceutical target for pain relief would be incredible news to people who do not respond well to opioid drugs, which have been the only option for decades. Much more work is needed before new drugs might materialize, but the finding that aldehydes play a role in inflammatory pain might be useful now—especially for people with conditions such as arthritis because it suggests they might reduce symptoms by avoiding alcohol.
