AMPK: An emerging target for modification of injury-induced pain plasticity

NEUROSCIENCE LETTERS

卷:557

Review

Price, Theodore J.^1,2,3  Dussor, Gregory^1,3 

[1] Univ Arizona, Sch Med, Dept Pharmacol, Tucson, AZ 85721 USA

[2] Univ Arizona, Inst Bio5, Sch Med, Tucson, AZ 85721 USA

[3] Univ Arizona, Grad Interdisciplinary Program Neurosci, Sch Med, Tucson, AZ 85721 USA

关键词: Chronic pain;    mTOR;    AMPK;    ERK;    Sodium channels;    Plasticity;   

DOI  :  10.1016/j.neulet.2013.06.060

来源: Elsevier

【 摘 要 】

Chronic pain is a critical medical problem afflicting hundreds of millions of people worldwide with costly effects on society and health care systems. Novel therapeutic avenues for the treatment of pain are needed that are directly targeted to the molecular mechanisms that promote and maintain chronic pain states. Recent evidence suggests that peripheral pain plasticity is promoted and potentially maintained via changes in translation control that are mediated by mTORC1 and MAPK pathways. While these pathways can be targeted individually, stimulating the AMPK pathway with direct or indirect activators achieves inhibition of these pathways via engagement of a single kinase. Here we review the form, function and pharmacology of AMPK with special attention to its emerging role as a potential target for pain therapeutics. We present the existing evidence supporting a role of AMPK activation in alleviating symptoms of peripheral nerve injury- and incision-induced pain plasticity and the blockade of the development of chronic pain following surgery. We argue that these preclinical findings support a strong rationale for clinical trials of currently available AMPK activators and further development of novel pharmacological strategies for more potent and efficacious manipulation of AMPK in the clinical setting. Finally, we posit that AMPK represents a unique opportunity for drug development in the kinase area for pain because it is pharmacologically manipulated via activation rather than inhibition potentially offering a wider therapeutic window with interesting additional pharmacological opportunities. Altogether, the physiology, pharmacology and therapeutic opportunities surrounding AMPK make it an attractive target for novel intervention for chronic pain and its prevention. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free