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Reactive aldehydes: an initial path to develop precision medicine for pain control
Vanessa O Zambelli1, Che-Hong Chen1, Eric R Gross1
11 Laboratory of Pain and Signaling, Butantan Institute, São Paulo 05503-900, Brazil ; 2 Department of Chemical and Systems Biology, 3 Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
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.
Insights
Reactive aldehydes contribute to pain sensation. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) metabolism of these aldehydes offers a target for pain management, especially for individuals with the ALDH2*2 variant.
Area of Science:
- Biochemistry
- Pain research
- Pharmacology
Background:
- Opioid-related risks necessitate novel pain treatment targets.
- Reactive aldehydes are implicated in pain signaling pathways.
- Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a role in aldehyde metabolism.
Purpose of the Study:
- To explore the role of reactive aldehydes in pain.
- To investigate the function of ALDH2 in regulating inflammatory pain.
- To discuss the clinical implications of ALDH2 variants in pain management.
Main Methods:
- Literature review and discussion in response to an editorial.
- Analysis of reactive aldehyde production and metabolism in pain.
- Examination of ALDH2 enzyme activity and its impact on pain.
Main Results:
- Reactive aldehyde production can initiate pain signaling.
- ALDH2 efficiently metabolizes reactive aldehydes, mitigating inflammatory pain.
- Inefficient metabolism due to ALDH2*2 variant affects approximately 540 million people.
Conclusions:
- Targeting ALDH2 offers a potential therapeutic strategy for pain control.
- ALDH2-targeted therapeutics could lead to precision medicine for pain.
- Understanding ALDH2's role is crucial for developing non-addictive pain treatments.
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