title: Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation.
abstract: We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. In healthy subjects, 957C>T influenced both innocuous and noxious thermal detection thresholds that were lowest in 957TT homozygotes (P values from .0277 to .0462). rTMS to S1 cortex had analgesic effect only in 957TT homozygote genotype (P=.0086). In patients, prevalence of 957TT homozygote genotype was higher than in a healthy Finnish population (50% vs 27%; P=.0191). Patients with 957TT genotype reported more severe pain than patients with other genotypes (P=.0351). COMT Val158Met polymorphism was not independently associated with the studied variables. Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain.
authors.affiliation: Department of Clinical Neurophysiology, Turku University Hospital and University of Turku, Turku, Finland. Electronic address: satu.jaaskelainen@tyks.fi.
authors.forename: Satu K
authors.initials: SK
authors.lastname: Jääskeläinen
authors.affiliation: Department of Neurology, Hospital District of South-Western Finland, Salo, Finland.
authors.forename: Pauliina
authors.initials: P
authors.lastname: Lindholm
authors.affiliation: Department of Diagnostic Radiology, Turku University Hospital, Turku, Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Valmunen
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Ullamari
authors.initials: U
authors.lastname: Pesonen
authors.affiliation: Department of Psychiatry, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Taiminen
authors.affiliation: Department of Statistics, University of Turku, Turku, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Virtanen
authors.affiliation: Department of Neurology, Hospital District of South-Western Finland, Salo, Finland.
authors.forename: Salla
authors.initials: S
authors.lastname: Lamusuo
authors.affiliation: Department of Oral Diseases, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Forssell
authors.affiliation: Pain Clinic, Turku University Hospital, Turku, Finland.
authors.forename: Nora
authors.initials: N
authors.lastname: Hagelberg
authors.affiliation: Department of Psychiatry, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D000328:Adult; D000368:Aged; D000698:Analgesia / Q000379:methods; D002394:Catechol O-Methyltransferase / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000235:genetics* / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D017288:Pain Threshold; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050781:Transcranial Magnetic Stimulation
chemical_list: D017448:Receptors, Dopamine D2; D002394:Catechol O-Methyltransferase
keywords: Brain dopamine system; Dopamine D2 receptor; Neuropathic pain; Quantitative sensory testing; Single nucleotide polymorphism 957C>T; Transcranial magnetic stimulation