Pain, while salient, is highly subjective. A sensation perceived as painful by one person may be perceived as uncomfortable, not painful or even pleasant to others. Within the same person, pain may also be modulated according to its threat value and the context in which it is presented. Imaging techniques, such as functional magnetic resonance imaging and positron emission tomography, have identified a distributed network in the brain, the pain-relevant brain regions, that encode the sensory-discriminative aspect of pain, as well as its cognitive and affective/emotional factors. Current knowledge also implicates the prefrontal cortex as the modulatory area for pain, with its subdivisions forming the cortico-cortical pathway, an alternative pain modulatory pathway distinct from the descending modulatory pathway of pain. These findings from neuroimaging in human subjects have paved the way for the molecular mechanisms of pain modulation to be explored in animal studies.
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