Chronic pain can develop from an acute pain state. The mechanisms mediating the transition from acute to chronic pain remain to be elucidated. Here, Parisien et al. focused on the immune system using samples from patients and animal models. Transcriptomic analysis in immune cells from subjects with low back pain showed that neutrophil activation–dependent inflammatory genes were up-regulated in subjects with resolved pain, whereas no changes were observed in patients with persistent pain. In rodents, anti-inflammatory treatments prolonged pain duration and the effect was abolished by neutrophil administration. Last, clinical data showed that the use of anti-inflammatory drugs was associated with increased risk of persistent pain, suggesting that anti-inflammatory treatments might have negative effects on pain duration.