n-(1-3-benzodioxol-5-ylmethyl)-2-6-dichlorobenzamide has been researched along with Acute-Pain* in 1 studies
1 other study(ies) available for n-(1-3-benzodioxol-5-ylmethyl)-2-6-dichlorobenzamide and Acute-Pain
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Aldehyde dehydrogenase-2 regulates nociception in rodent models of acute inflammatory pain.
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 ~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. Topics: Acetaldehyde; Acute Pain; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Animals; Behavior, Animal; Benzamides; Benzodioxoles; Disease Models, Animal; Enzyme Activation; Formaldehyde; Heterozygote; Hyperalgesia; Inflammation; Mice, Inbred C57BL; Mitochondrial Proteins; Nociception; Rats | 2014 |