| Texto completo | |
| Autor(es): |
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]
Número total de Autores: 6
|
| Afiliação do(s) autor(es): | [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
Número total de Afiliações: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Science Translational Medicine; v. 6, n. 251 AUG 27 2014. |
| Citações Web of Science: | 32 |
| Resumo | |
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) | |
| Processo FAPESP: | 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular |
| Beneficiário: | Hugo Aguirre Armelin |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |
| Processo FAPESP: | 11/08873-8 - Papel da aldeído desidrogenase 2 e do 4-hidroxinonenal na dor |
| Beneficiário: | Vanessa Olzon Zambelli |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 12/05035-4 - Papel da aldeído desidrogenase 2 e do 4-hidroxinonenal na dor |
| Beneficiário: | Yara Cury |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |