The neurobiology of central sensitization

Abstract

Central sensitization refers to the amplification of pain by central nervous system mechanisms. Classically described as a consequence of ongoing nociceptive input, it is increasingly recognized that central sensitization also occurs independent of peripheral injury or inflammation. Features of central sensitization have been identified in nearly all chronic pain conditions, and it is considered the primary underlying cause of pain in conditions such as fibromyalgia. Central sensitization is characterized in these conditions by widespread pain and multisite hyperalgesia/allodynia. Co-occurring symptoms include fatigue, mood and cognitive problems, sleep disturbances, and multisensory hypersensitivity. Individuals with central sensitization often report previous exposure to psychosocial or physical stressors, and a higher personal lifetime and family history of pain, with the latter findings supported by genetic studies. Neuroimaging studies of central sensitization show evidence of: changes in brain gray matter in pain processing regions; neurochemical imbalances; and altered resting brain-network connectivity between pronociceptive and antinociceptive brain areas. Immune system abnormalities have also been demonstrated in individuals with central sensitization. The recognition of central sensitization, and whether it is being driven by ongoing nociceptive input or it is occurring in the absence of a peripheral driver, is critical for effective pain management.