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.
Highlights
IntroductionExperimental fear conditioning has proven to be a valuable tool for studying the neurobiological underpinnings of (pain-related) fear, anxiety, specific phobias, and placebo analgesia. (Cheng et al, 2003; Phelps et al, 2004; Delgado et al, 2006; Bradley et al, 2008; Schiller et al, 2008; Lui et al, 2010; De Peuter et al, 2011; Schweckendiek et al, 2011; Dunsmoor et al, 2013)
In a subsequent region-of-interest (ROI) analysis, we investigated the following bilateral brain structures: amygdala, insula, anterior cingulate cortex (ACC), orbital frontal cortex (OFC), thalamus, and the medial prefrontal cortex (mPFC)
Pre- and postexperiment pain matching revealed that slightly higher currents were needed for the canine tooth to reach the transition point compared with tibial stimulations (Figure 4)
Summary
Experimental fear conditioning has proven to be a valuable tool for studying the neurobiological underpinnings of (pain-related) fear, anxiety, specific phobias, and placebo analgesia. (Cheng et al, 2003; Phelps et al, 2004; Delgado et al, 2006; Bradley et al, 2008; Schiller et al, 2008; Lui et al, 2010; De Peuter et al, 2011; Schweckendiek et al, 2011; Dunsmoor et al, 2013). A constellation of other structures such as the orbital frontal cortex (OFC), the thalamus, anterior cingulate cortex (ACC), the insula and the medial prefrontal cortex (mPFC) are linked to aspects of fear conditioning (Davis and Whalen, 2001; Phelps et al, 2004; Sehlmeyer et al, 2009; Guhn et al, 2014). These structures modulate fear responses and extend them to the wider context of the conditioning (Fiddick, 2011)
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