Roles of AMPK and Its Downstream Signals in Pain Regulation

Pain is an unpleasant sensory and emotional state that decreases quality of life. A metabolic sensor, adenosine monophosphate-activated protein kinase (AMPK), which is ubiquitously expressed in mammalian cells, has recently attracted interest as a new target of pain research. Abnormal AMPK expression and function in the peripheral and central nervous systems are associated with various types of pain. AMPK and its downstream kinases participate in the regulation of neuron excitability, neuroinflammation and axonal and myelin regeneration. Numerous AMPK activators have reduced pain behavior in animal models. The current understanding of pain has been deepened by AMPK research, but certain issues, such as the interactions of AMPK at each step of pain regulation, await further investigation. This review examines the roles of AMPK and its downstream kinases in neurons and non-neuronal cells, as well as their contribution to pain regulation.