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

Persistent Link:
http://hdl.handle.net/10150/610214
Title:
Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain
Author:
Melemedjian, Ohannes; Asiedu, Marina; Tillu, Dipti; Sanoja, Raul; Yan, Jin; Lark, Arianna; Khoutorsky, Arkady; Johnson, Jessica; Peebles, Katherine; Lepow, Talya; Sonenberg, Nahum; Dussor, Gregory; Price, Theodore
Affiliation:
Department of Pharmacology, University of Arizona, N Campbell Ave, Tucson, 85724, USA; Department of Biochemistry, McGill University, Sir William Osler, Montreal, H3G 1Y6, Canada; Goodman Cancer Research Centre, McGill University, McGill University, Sir William Osler, Montreal, H3G 1Y6, Canada; Graduate Interdisciplinary Program in Neuroscience, University of Arizona, N Campbell Ave, Tucson, 85724, USA; Bio5 Institute, University of Arizona, N Campbell Ave, Tucson, 85724, USA
Issue Date:
2011
Publisher:
BioMed Central
Citation:
Melemedjian et al. Molecular Pain 2011, 7:70 http://www.molecularpain.com/content/7/1/70
Journal:
Molecular Pain
Rights:
© 2011 Melemedjian et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
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.
EISSN:
1744-8069
DOI:
10.1186/1744-8069-7-70
Version:
Final published version
Additional Links:
http://mpx.sagepub.com/content/7/1744-8069-7-70.full

Full metadata record

DC FieldValue Language
dc.contributor.authorMelemedjian, Ohannesen
dc.contributor.authorAsiedu, Marinaen
dc.contributor.authorTillu, Diptien
dc.contributor.authorSanoja, Raulen
dc.contributor.authorYan, Jinen
dc.contributor.authorLark, Ariannaen
dc.contributor.authorKhoutorsky, Arkadyen
dc.contributor.authorJohnson, Jessicaen
dc.contributor.authorPeebles, Katherineen
dc.contributor.authorLepow, Talyaen
dc.contributor.authorSonenberg, Nahumen
dc.contributor.authorDussor, Gregoryen
dc.contributor.authorPrice, Theodoreen
dc.date.accessioned2016-05-20T09:01:17Z-
dc.date.available2016-05-20T09:01:17Z-
dc.date.issued2011en
dc.identifier.citationMelemedjian et al. Molecular Pain 2011, 7:70 http://www.molecularpain.com/content/7/1/70en
dc.identifier.doi10.1186/1744-8069-7-70en
dc.identifier.urihttp://hdl.handle.net/10150/610214-
dc.description.abstractNeuropathic 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.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://mpx.sagepub.com/content/7/1744-8069-7-70.fullen
dc.rights© 2011 Melemedjian et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleTargeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic painen
dc.typeArticleen
dc.identifier.eissn1744-8069en
dc.contributor.departmentDepartment of Pharmacology, University of Arizona, N Campbell Ave, Tucson, 85724, USAen
dc.contributor.departmentDepartment of Biochemistry, McGill University, Sir William Osler, Montreal, H3G 1Y6, Canadaen
dc.contributor.departmentGoodman Cancer Research Centre, McGill University, McGill University, Sir William Osler, Montreal, H3G 1Y6, Canadaen
dc.contributor.departmentGraduate Interdisciplinary Program in Neuroscience, University of Arizona, N Campbell Ave, Tucson, 85724, USAen
dc.contributor.departmentBio5 Institute, University of Arizona, N Campbell Ave, Tucson, 85724, USAen
dc.identifier.journalMolecular Painen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.