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2013
Journal Article
Titel
Activation of the AMP-Activated Protein Kinase Reduces Inflammatory Nociception
Abstract
The activation of the adenosine monophosphate (AMP)-activated kinase (AMPK) has been associated with beneficial effects such as improvement of hyperglycemic states in diabetes as well as reduction of obesity and inflammatory processes. Recent studies provide evidence for a further role of AMPK in models of acute and neuropathic pain. In this study, we investigated the impact of AMPK on inflammatory nociception. Using 5-amino-1-v-d-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin as AMPK activators, we observed anti-inflammatory and antinociceptive effects in 2 models of inflammatory nociception. The effects were similar to those observed with the standard analgesic ibuprofen. The mechanism appears to be based on regulation of the AMPKa2 subunit of the kinase because AMPKa2 knockout mice showed increased nociceptive responses that could not be reversed by the AMPK activators. On the molecular level, antinociceptive effects are at least partially mediated by reduced activation of different MAP-kinases in the spinal cord and a subsequent decrease in pain-relevant induction of c-fos, which constitutes a reliable marker of elevated activity in spinal cord neurons following peripheral noxious stimulation. In summary, our results indicate that activation of AMPKa2 might represent a novel therapeutic option for the treatment of inflammation-associated pain, providing analgesia with fewer unwanted side effects.