The potent, indirect adenosine monophosphate- activated protein kinase activator R419 attenuates mitogen-activated protein kinase signaling, inhibits nociceptor excitability, and reduces pain hypersensitivity in mice.

ABSTRACT: There is a great need for new therapeutics for the treatment of pain. A possible avenue to development of such therapeutics is to interfere with signaling pathways engaged in peripheral nociceptors that cause these neurons to become hyperexcitable. There is strong evidence that mitogen activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K) / mechanistic target of rapamycin (mTOR) signaling pathways are key modulators of nociceptor excitability in vitro and in vivo. Activation of adenosine monophosphate activated protein kinase (AMPK) can inhibit signaling in both of these pathways and AMPK activators have been shown to inhibit nociceptor excitability and pain hypersensitivity in rodents. R419 is one of, if not the most potent AMPK activator described to date.

SUBMITTER: Mejia GL 

PROVIDER: S-EPMC5034875 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature