Differential role of adenosine signaling cascade in acute and chronic pain

Adenosine is a signaling molecule induced under stress such as energy insufficiency and ischemic/hypoxic conditions. Adenosine controls multiple physiological and pathological cellular and tissue function by activation of four G protein-coupled receptors (GPCR). Functional role of adenosine signaling in acute pain has been widely studied. However, the role of adenosine signaling in chronic pain is poorly understood. At acute levels, adenosine can be beneficial to anti-pain whereas a sustained elevation of adenosine can be detrimental to promote chronic pain. In recent years, extensive progress has been made to define the role of adenosine signaling in chronic pain and to dissect molecular new insight underlying the development of chronic pain. In this review, we summarize the differential role of adenosine signaling cascade in acute and chronic pain with a major focus on recent studies revealing adenosine ADORA2B receptor activation in the pathology of chronic pain. We further provide a therapeutic outlook of how multiple adenosine signaling components can be useful to treat chronic pain.