Abstract
Today's treatment for chronic pain is inadequate, and novel targets need to be identified. This requires a better understanding of the mechanisms involved in pain sensitization and chronification. In this review, we discuss how peripheral inflammation, as occurs during an infection, modulates the central pain system. In rodents, neonatal inflammation leads to increased pain sensitivity in adulthood by priming immune components both peripherally and centrally. The excitability of neurons in the spinal cord is also altered by neonatal inflammation and may add to pain sensitization later in life. In adult humans, inflammation modulates pain sensitivity as well, partly by affecting the activity in brain areas that process and regulate pain signals. Low-grade inflammation is common in clinical populations both peripherally and centrally, and priming of the immune system has also been suggested in some pain populations. The nociceptive and immune systems are primed by infections and inflammation. The early life programming of nociceptive responses following exposure to infections or inflammation will define individual differences in adult pain perception. Immune-to-brain mechanisms and neuroimmune pathway need further investigation as they may serve both as predictors and therapeutic targets in chronic pain.