Structural plasticity and reorganisation in chronic pain

Key Points The transition from acute to chronic pain is associated with structural plasticity or circuit reorganisation at various points in somatosensory pain circuits. Peripheral sensory neurons and axons exhibit diverse types of structural changes that are specific to different types of chronic pain. Structural remodelling of synaptic contacts on spinal dorsal horn neurons is causally associated with nociceptive hypersensitivity. Neuropathic pain is associated with the reorganization of cortical sensory maps. Chronic pain is characterized by increased pain-related activation of emotional networks in the brain. Pain disrupts structural and functional brain connectivity, which can be restored with effective treatment. The mechanisms that underlie the transition of acute pain to a chronic intractable disorder are not well understood. In this Review, Kuner and Flor discuss how structural plasticity and reorganisation in somatosensory and emotional networks can contribute to chronic pain, integrating information available from animal models and human patients. Chronic pain is not simply a temporal continuum of acute pain. Studies on functional plasticity in neural circuits of pain have provided mechanistic insights and linked various modulatory factors to a change in perception and behaviour. However, plasticity also occurs in the context of structural remodelling and reorganisation of synapses, cells and circuits, potentially contributing to the long-term nature of chronic pain. This Review discusses maladaptive structural plasticity in neural circuits of pain, spanning multiple anatomical and spatial scales in animal models and human patients, and addresses key questions on structure–function relationships.