Striatal dopamine D2/D3 receptor availability correlates with individual response characteristics to pain.
We studied in healthy humans the contribution of cerebral dopamine D2/D3 receptors to individual differences in response characteristics to painful stimulation. Positron emission tomography was used to measure the dopamine D2/D3 binding potential (D2/D3 BP) with [(11)C]raclopride in the striatum (n = 8) and with [(11)C]FLB 457 in the extrastriatal regions (n = 11). Sensitivity to cutaneous heat pain was assessed by a traditional threshold method and by an analysis based on the signal detection theory which allows the separation of an individual subject's discriminative capacity from the response criterion, i.e. the area under the receiver operating characteristic curve provides a measure of the sensory discriminability (sensory factor) and the response criterion gives an estimate of the subject's response bias or attitude (nonsensory factor). The pain threshold and response criterion were inversely correlated with the D2/D3 BP in the right putamen, whereas the discriminative capacity was not significantly correlated with the D2/D3 BP in any brain region. The correlation of the D2/D3 BP in the putamen with the pain threshold and the subject's response criterion may rather be explained by a dopaminergic effect on nonsensory factors determining the subject's attitude towards pain than by a dopaminergic effect on the subject's discriminative capacity. Alternatively, striatal dopamine D2/D3 receptors could control a modulatory pathway producing a parallel shift in the stimulus-response function for sensory signals, mimicking a change in the subject's response criterion.
Pertovaara
Antti
A
Department of Physiology, Institute of Biomedicine, University of Turku, Jiinamyllynkatu 10, FIN-20520 Turku, Finland. Antti.Pertovaara@utu.fi
Martikainen
Ilkka K
IK
Hagelberg
Nora
N
Mansikka
Heikki
H
Någren
Kjell
K
Hietala
Jarmo
J
Scheinin
Harry
H
D000328:Adult; D019540:Area Under Curve; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D010146:Pain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology*; D049268:Positron-Emission Tomography / Q000379:methods; D011759:Pyrrolidines / Q000493:pharmacokinetics; D012372:ROC Curve; D020891:Raclopride / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C065065:FLB 457; D020891:Raclopride