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Open Access 01-12-2011 | Research

Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain

Authors: Ohannes K Melemedjian, Marina N Asiedu, Dipti V Tillu, Raul Sanoja, Jin Yan, Arianna Lark, Arkady Khoutorsky, Jessica Johnson, Katherine A Peebles, Talya Lepow, Nahum Sonenberg, Gregory Dussor, Theodore J Price

Published in: Molecular Pain | Issue 1/2011

Abstract

Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. We hypothesized that dysregulated translation regulation pathways may underlie neuropathic pain. Peripheral nerve injury induced reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity, increased phosphorylation of mTOR and ERK downstream targets, augmented eIF4F complex formation and enhanced nascent protein synthesis. The AMP activated protein kinase (AMPK) activators, metformin and A769662, inhibited translation regulation signaling pathways, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia. Therefore, injury-induced dysregulation of translation control underlies pathology leading to neuropathic pain and reveals AMPK as a novel therapeutic target for the potential treatment of neuropathic pain.

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Title: Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain
Authors: Ohannes K Melemedjian
Marina N Asiedu
Dipti V Tillu
Raul Sanoja
Jin Yan
Arianna Lark
Arkady Khoutorsky
Jessica Johnson
Katherine A Peebles
Talya Lepow
Nahum Sonenberg
Gregory Dussor
Theodore J Price
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2011
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-7-70

2024 ASCO Annual Meeting

Springer Medicine

Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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