A peripheral injury drives neuroimmune interactions at the level of the injury and throughout the neuraxis. Understanding these systems will be beneficial in the pursuit to target persistent pain that involves both neural and immune components. In this review, we discuss the impact of injury on the development of neuroimmune signaling, along with data that suggest a possible cellular immune memory. We also discuss the parallel effects of injury in the nervous system and immune related areas including bone marrow, lymph node and central nervous system-related cells. Finally, we relate these findings to patient populations and current research that evaluates human tissue.