This chapter reviews the evidence on plastic changes along the neuraxis and their relationship to pain in humans. It delineates treatment approaches that are designed less towards analgesia but more towards reversing maladaptive plasticity with the hypothesis that this would consequently also reduce chronic pain and extinguish pain memories. Implicit pain memories can be established and altered by learning processes such as habituation and sensitization, operant and classical conditioning or priming. The chapter suggests that the alteration of somatosensory pain memories might be an influential method to reduce both chronic musculoskeletal and neuropathic pain. Cortical plasticity related to chronic pain can be modified by behavioral interventions that provide feedback to the brain areas that were altered by somatosensory pain memories or by pharmacologic agents that prevent or reverse maladaptive memory formation. Future research needs to focus on emotional changes that contribute to and interact with the sensory and motor changes.