title: Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex in man.
abstract: Relatively little is known on pain-induced neurotransmitter release in the human cerebral cortex. We used proton magnetic resonance spectroscopy (1H-MRS) during tonic painful heat stimulation to test the hypothesis of increases in both glutamate and GABA, two neurotransmitters with a key role in pain processing. Using a 3T MR scanner, we acquired spectra from the rostral anterior cingulate cortex (rACC) in 13 healthy right-handed subjects at rest and during painful heat stimulation. The painful stimulus consisted of a suprathreshold painful tonic heat pulse, which was delivered to the right upper leg via a fMRI-compatible Peltier element. Compared to non-painful stimulation, painful tonic heat was associated with a significant increase in GABA concentrations in the rACC. No changes in glutamate concentrations were detected during noxious stimulation. This study provides the first evidence that GABA is released in the human cerebral cortex during painful stimulation. The results are in line with animal findings on the role of GABA in pain processing and with studies in humans showing analgesic efficacy of GABA-related drugs in clinical pain conditions.
authors.affiliation: Department of Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark. ron@pet.rh.dk
authors.forename: Ron
authors.initials: R
authors.lastname: Kupers
authors.forename: Else R
authors.initials: ER
authors.lastname: Danielsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Kehlet
authors.forename: Rune
authors.initials: R
authors.lastname: Christensen
authors.forename: Carsten
authors.initials: C
authors.lastname: Thomsen
mesh_terms: D000328:Adult; D001931:Brain Mapping; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D017397:Prefrontal Cortex / Q000098:blood supply / Q000378:metabolism*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D010100:Oxygen