There is a large body of evidence that serotonin [5-hydroxytryptamine (5-HT)] 
plays an important role in the transmission and regulation of pain. Here we used 
positron emission tomography (PET) to study the relationship between baseline 
5-HT(2A) binding in the brain and responses to noxious heat stimulation in a 
group of young healthy volunteers. Twenty-one healthy subjects underwent PET 
scanning with the 5-HT(2A) antagonist, [(18)F]altanserin. In addition, 
participants underwent a battery of pain tests using noxious heat stimulation to 
assess pain threshold, pain tolerance and response to short-lasting phasic and 
long-lasting (7-minute) tonic painful stimulation. Significant positive 
correlations were found between tonic pain ratings and [(18)F]altanserin binding 
in orbitofrontal (r=0.66; p=0.005), medial inferior frontal (r=0.60; p=0.014), 
primary sensory-motor (r=0.61; p=0.012) and posterior cingulate (r=0.63; 
p=0.009) cortices. In contrast, measures of regional [(18)F]altanserin binding 
did not correlate with pain threshold, pain tolerance, or suprathreshold phasic 
pain responses. These data suggest that cortical 5-HT(2A) receptor availability 
co-varies with responses to tonic pain. The correlation between 
[(18)F]altanserin binding in prefrontal cortex and tonic pain suggests a 
possible role of this brain region in the modulation and/or cognitive-evaluative 
appreciation of pain.