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Pain is defined as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”. This complex perception arises from the coordinated activity of several brain areas processing either sensory–discriminative or affective–motivational components. Functional studies performed in healthy volunteers revealed that affective–emotional components of pain are processed bilaterally but present a clear lateralization towards the right hemisphere, regardless of the site of stimulation. Studies at the cellular level performed in experimental animal models of pain have shown that neuronal activity in the right amygdala is clearly pronociceptive, whilst activation of neurons in the left amygdala might even exert antinociceptive effects. A shift in lateralization becomes evident during the development of chronic pain; thus, in patients with neuropathic pain symptoms, there is increased activity in ipsilateral brain areas related with pain. These observations extend the asymmetrical left–right lateralization within the nervous system and provide a new hypothesis for the pathophysiology of chronic forms of pain. In this article, we will review experimental data from preclinical and human studies on functional lateralization in the brain during pain processing, which will help to explain the affective disorders associated with persistent, chronic pain.

Asymmetric Lateralization during Pain Processing