title: Equal pain-Unequal fear response: enhanced susceptibility of tooth pain to fear conditioning.
abstract: Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS) applied to the right maxillary canine (UCS-c) vs. the right tibia (UCS-t). For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+). Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were (1) skin conductance changes and (2) time-dependent brain activity (BOLD responses) in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex, and medial prefrontal cortex. A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses) in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point toward a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.
authors.affiliation: Center of Dental Medicine, Clinic for Removable Prosthodontics, Masticatory Disorders and Special Care Dentistry, University of Zurich Zurich, Switzerland ; Chiropractic Medicine, Balgrist University Hospital Zurich, Switzerland.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Meier
authors.affiliation: Center of Dental Medicine, Clinic for Removable Prosthodontics, Masticatory Disorders and Special Care Dentistry, University of Zurich Zurich, Switzerland.
authors.forename: Nuno M P
authors.initials: NM
authors.lastname: de Matos
authors.affiliation: Center of Dental Medicine, Clinic for Removable Prosthodontics, Masticatory Disorders and Special Care Dentistry, University of Zurich Zurich, Switzerland ; MRI Technology, Institute for Biomedical Engineering, Swiss Federal Institute of Technology and the University of Zurich Zurich, Switzerland.
authors.forename: Mike
authors.initials: M
authors.lastname: Brügger
authors.affiliation: Center of Dental Medicine, Clinic for Removable Prosthodontics, Masticatory Disorders and Special Care Dentistry, University of Zurich Zurich, Switzerland.
authors.forename: Dominik A
authors.initials: DA
authors.lastname: Ettlin
authors.affiliation: Center of Dental Medicine, Clinic for Removable Prosthodontics, Masticatory Disorders and Special Care Dentistry, University of Zurich Zurich, Switzerland.
authors.forename: Nenad
authors.initials: N
authors.lastname: Lukic
authors.affiliation: Institute of Psychology, Department of Neuropsychology, University of Zurich Zurich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Cheetham
authors.affiliation: Institute of Psychology, Department of Neuropsychology, University of Zurich Zurich, Switzerland.
authors.forename: Lutz
authors.initials: L
authors.lastname: Jäncke
authors.affiliation: Institute of Psychology, Department of Neuropsychology, University of Zurich Zurich, Switzerland ; Center for Neurology and Rehabilitation Cereneo Vitznau, Switzerland.
authors.forename: Kai
authors.initials: K
authors.lastname: Lutz
keywords: amygdala; dental phobia; fMRI; fear conditioning; medial prefrontal cortex (mPFC); pain; skin conductance response; tooth
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