Summary of Changes in Neural Function following Nerve Injury. In the Normal State, such as the response to noxious heat (left panel), the pain system provides salient information on the nature of the stimulus, the context of the stimulus, and the emotional response to the stimulus. In the chronic pain state, for example after nerve injury (right panel), changes occur along the neural axis. In the peripheral nerve there may be loss of fibers (1), changes in function of neurons in the dorsal root ganglion (2), and alterations in the dorsal horn (3). In the central nervous system, there are changes in dorsal horn (non-afferent inputs) as well as changes in sensory processing (e.g., hyperalgesia (3 and 5)) and emotional processing (5). These changes also result in an alteration of descending modulatory influences (4) from a number of central nervous system structures (e.g., cingulate, frontal cortex, amygdala etc). The constellation of changes in peripheral and central nervous systems result in changes to the pain intensity during spontaneous and evoked pain, and emotional processing (e.g., altered reward or hedonic state) that may lead to changes in comorbid disease in chronic pain (e.g., depression or anxiety).