The Effects of Extended Pain on Behavior: Recent Progress.

Chronic pain is frequently associated with anxiety, depression, and cognitive dysfunction. This review discusses recent work in rodents that contributes to the understanding of their neurobiological links. Brain regions that contain circuits that mediate persistent changes in behavior that are caused by nerve injury or joint inflammation include the rostral anterior cingulate and other parts of the medial prefrontal cortex, the basolateral and central nucleus of the amygdala, and the nucleus accumbens. Functional changes, including increases in the activity within specific neuronal pathways and in the levels of specific synaptic components, that are associated with the behavior changes, or are in some cases necessary for them, have recently been identified. Broadly projecting modulatory systems and widely expressed factors such as cytokines and growth factors also contribute to pain-associated behavior. Integrating these observations and determining their causal relationships is now critical for the identification of therapeutic targets and the design of appropriate interventions.