title: Imaging pain modulation by subanesthetic S-(+)-ketamine.
abstract: Little is known about the effects of low-dose S-(+)-ketamine on the cerebral processing of pain. We investigated the effects of subanesthetic IV S-(+)-ketamine doses on the perception of experimental painful heat stimuli. Healthy volunteers were evaluated with functional magnetic resonance imaging (fMRI) while receiving the painful stimuli in conjunction with placebo and increasing doses (0.05, 0.1, 0.15 mg x kg(-1) x h(-1)) of ketamine infusion. Vital variables were monitored and all subjects rated pain intensity and unpleasantness on a numerical rating scale. Alterations in consciousness were measured using a psycho-behavioral questionnaire. Pain unpleasantness declined as ketamine dosage was increased (55.1% decrease, placebo versus 0.15 mg x kg(-1) x h(-1) ketamine). Pain intensity ratings also decreased with increasing ketamine dosage but to a lesser extent (23.1% decrease). During placebo administration, a typical pain activation network (thalamus, insula, cingulate, and prefrontal cortex) was found, whereas decreased pain perception with ketamine was associated with a dose-dependent reduction of pain-induced cerebral activations. Analysis of the dose-dependent ketamine effects on pain processing showed a decreasing activation of the secondary somatosensory cortex (S2), insula and anterior cingulate cortex. This part of the anterior cingulate cortex (midcingulate cortex) has been linked with the affective pain component that underlines the potency of ketamine in modulating affective pain processing.
authors.affiliation: Neurologische Klinik und Poliklinik, Technische Universität München, Germany. sprenger@lrz.tu-muenchen.de
authors.forename: Till
authors.initials: T
authors.lastname: Sprenger
authors.forename: Michael
authors.initials: M
authors.lastname: Valet
authors.forename: Ralph
authors.initials: R
authors.lastname: Woltmann
authors.forename: Claus
authors.initials: C
authors.lastname: Zimmer
authors.forename: Rainer
authors.initials: R
authors.lastname: Freynhagen
authors.forename: Eberhard F
authors.initials: EF
authors.lastname: Kochs
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Tölle
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000700:Analgesics / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation* / Q000379:methods*; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D010865:Pilot Projects; D010919:Placebos
chemical_list: D000700:Analgesics; D010919:Placebos; D007649:Ketamine