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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Aldehyde dehydrogenase-2 regulates nociception in rodent models of acute inflammatory pain

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Author(s):
Zambelli, Vanessa O. [1, 2] ; Gross, Eric R. [1, 3] ; Chen, Che-Hong [1] ; Gutierrez, Vanessa P. [2] ; Cury, Yara [2] ; Mochly-Rosen, Daria [1]
Total Authors: 6
Affiliation:
[1] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 - USA
[2] Butantan Inst, Lab Pain & Signaling, BR-05503900 Sao Paulo - Brazil
[3] Stanford Univ, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Stanford, CA 94305 - USA
Total Affiliations: 3
Document type: Journal article
Source: Science Translational Medicine; v. 6, n. 251 AUG 27 2014.
Web of Science Citations: 32
Abstract

Exogenous aldehydes can cause pain in animal models, suggesting that aldehyde dehydrogenase-2 (ALDH2), which metabolizes many aldehydes, may regulate nociception. To test this hypothesis, we generated a knock-in mouse with an inactivating point mutation in ALDH2 (ALDH2{*}2), which is also present in human ALDH2 of similar to 540 million East Asians. The ALDH2{*}1/{*}2 heterozygotic mice exhibited a larger response to painful stimuli than their wild-type littermates, and this heightened nociception was inhibited by an ALDH2-selective activator (Alda-1). No effect on inflammation per se was observed. Using a rat model, we then showed that nociception tightly correlated with ALDH activity (R-2 = 0.90) and that reduced nociception was associated with less early growth response protein 1 (EGR1) in the spinal cord and less reactive aldehyde accumulation at the insult site (including acetaldehyde and 4-hydroxynonenal). Further, acetaldehyde-and formalin-induced nociceptive behavior was greater in the ALDH2{*}1/{*}2 mice than in the wild-type mice. Finally, Alda-1 treatment was even beneficial when given after the inflammatory agent was administered. Our data in rodent models suggest that the mitochondrial enzyme ALDH2 regulates nociception and could serve as a molecular target for pain control, with ALDH2 activators, such as Alda-1, as potential non-narcotic, cardiac-safe analgesics. Furthermore, our results suggest a possible genetic basis for East Asians' apparent lower pain tolerance. (AU)

FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/08873-8 - The role of aldehyde dehydrogenase 2 and 4- hydroxynonenal in pain
Grantee:Vanessa Olzon Zambelli
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 12/05035-4 - Role of aldehyde desidrogenase-2 and 4-hydroxynonenal on pain
Grantee:Yara Cury
Support Opportunities: Regular Research Grants