title: A PET [18F]altanserin study of 5-HT2A receptor binding in the human brain and responses to painful heat stimulation.
abstract: 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.
authors.affiliation: Department for Surgical Pathophysiology, University of Copenhagen, Denmark. ron@pet.rh.dk
authors.forename: Ron
authors.initials: R
authors.lastname: Kupers
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.forename: Arne
authors.initials: A
authors.lastname: Naert
authors.forename: Rune
authors.initials: R
authors.lastname: Christensen
authors.forename: Esben
authors.initials: E
authors.lastname: Budtz-Joergensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Kehlet
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006358:Hot Temperature; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin