Here we review the literature assessing the roles of the brain dopaminergic and serotonergic systems in the modulation of
pain as revealed by in vivo human studies using positron emission tomography. In healthy subjects,
dopamine D2/D3 receptor availability particularly in the striatum and
serotonin 5-HT1A and
5-HT2A receptor availabilities in the cortex predict the subject's response to tonic experimental
pain. High availability of
dopamine D2/D3 or
serotonin 5-HT2A receptors is associated with high
pain intensity, whereas high availability of 5-HT1A receptors associates with low
pain intensity. Chronic
neuropathic pain is associated with high striatal
dopamine D2/D3 receptor availability, for which low endogenous
dopamine tone is a plausible explanation, although a compensatory increase in striatal
dopamine D2/D3 receptor density may also contribute. In contrast, chronic
musculoskeletal pain is associated with low baseline availability of striatal
dopamine D2/D3 receptors. In healthy subjects, brain
serotonin 5-HT1A as well as
dopamine D2/D3 receptor availabilities associate with the subject's response criterion rather than the capacity to discriminate painful thermal stimuli suggesting that these
neurotransmitter systems act mainly on non-sensory rather than sensory factors of thermally induced
pain experience. Additionally,
5-HT1A receptor availability predicts the subject's discriminative ability but not response criterion for non-painful tactile test stimuli, while no such correlation is observed with
dopamine D2/D3 receptors. These findings suggest that
dopamine acting on striatal
dopamine D2/D3 receptors and
serotonin acting on cortical 5-HT1A and 5-HT2A receptors contribute to top-down
pain regulation in humans.