Affective and Sensory Disorders in Pain Processing: Higher Brain and Brainstem Circuits that Regulate Pain Inhibition and Facilitation

The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. I will describe time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion. In acute pain, the LC promotes feedback inhibition of nociception due to the activation of the descending pain pathway to the spinal cord. As time passes after injury, endogenous LC analgesia fails, and it promotes pain facilitation through the dorsal reticular nucleus (DRt). Anterior cingulate cortex (ACC) or basolateral amygdala (BLA) activity contributes to anxiety, increasing aversive learning and memory, and behavioral despair, sharing similarities with stress-related disorders. These data demonstrate the functional heterogeneity of the LC output in pain that will be of interest when designing therapeutic strategies. Thus, exogenous activation of the LC→spinal cord projection can relieve pain, while the activation of other structures (prefrontal cortex or BLA) may produce adverse effects.