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Targeting AMPK for the Alleviation of Pathological Pain

Chapter
First Online:
Part of the Experientia Supplementum book series (EXS, volume 107)

Abstract

Chronic pain is a major clinical problem that is poorly treated with available therapeutics. Adenosine monophosphate-activated protein kinase (AMPK) has recently emerged as a novel target for the treatment of pain with the exciting potential for disease modification. AMPK activators inhibit signaling pathways that are known to promote changes in the function and phenotype of peripheral nociceptive neurons and promote chronic pain. AMPK activators also reduce the excitability of these cells suggesting that AMPK activators may be efficacious for the treatment of chronic pain disorders, like neuropathic pain, where changes in the excitability of nociceptors is thought to be an underlying cause. In agreement with this, AMPK activators have now been shown to alleviate pain in a broad variety of preclinical pain models indicating that this mechanism might be engaged for the treatment of many types of pain in the clinic. A key feature of the effect of AMPK activators in these models is that they can lead to a long-lasting reversal of pain hypersensitivity even long after treatment cessation, indicative of disease modification. Here, we review the evidence supporting AMPK as a novel pain target pointing out opportunities for further discovery that are likely to have an impact on drug discovery efforts centered around potent and specific allosteric activators of AMPK for chronic pain treatment.

Keywords

Neuropathic pain Cancer pain; AMPK mTOR MAPK Postsurgical pain 
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Notes

Acknowledgements

This work was supported by NIH grants R01NS065926 (TJP), R01GM102575 (TJP and GD), and The University of Texas STARS program (TJP and GD).

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. 1.University of Texas at Dallas, School of Behavioral and Brain SciencesRichardsonUSA

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