Abstract
Chronic pain is subserved by interactions between the immune and nervous systems. There has been an historical emphasis on the disordered pro-inflammatory mechanisms that maintain chronic pain. This narrative review will highlight the adaptive benefit of initial pro-inflammatory signaling for the long-term trajectory of pain, as well as pro-resolving mechanisms that can prevent pain from becoming chronic. Importantly, there is potential for these insights to be harnessed for safe, nonaddictive, disease-modifying treatment of pain.