Neuro-genetics of persistent pain

Pain is a complex consciousness that emerges from the brain, and is commonly a result of nociception; the physiological process initiated by activation of specialised high-threshold peripheral sensory neurons. When pain is persistent, its affective aspects can dominate and cause considerable suffering. This chronic pain state is not an inevitable consequence of physical injury or disease. Instead, susceptibility to chronic pain results from complex interactions between multiple genes and the environment that influence nociception and regulate the consciousness of pain. The biological bases for chronic pain can now be defined and measured by brain neuroimaging at a systems level, where penetrance of genetic variation should be higher when compared to syndromal phenotypes. To date, very few neuroimaging studies have attempted to connect brain activity associated with pain to genes. We review these together with other pertinent studies here, and suggest how neuroimaging endophenotypes might prove useful for the development of treatments for chronic pain.

► Nociception is neither necessary nor sufficient for pain. ► Pain can persist long after physical injury. ► Complex genes-environment interactions determine vulnerability to chronic pain. ► Brain neuroimaging defines key biological systems that underlie chronic pain. ► Neuroimaging endophenotypes can link genetics to complex pain syndromes and behaviour.