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.

The Human Brain Response to Dental Pain Relief

“…The methodological novelty and particular strength of the present study is that many confounders were eliminated by applying a constant and purely noxious stimulus to the tooth and subsequently blocking the nociceptive signaling by an articaine injection. The stimulus type selection was based on previous findings demonstrating that electrical dental pulp stimuli evoke sensory perceptions that are highly stable across time (Brown et al, 1985;Brugger et al, 2012;Meier et al, 2014). No pain rating was therefore required that could have caused blurring effects on fMRI findings due to cognitive and motor aspects of the rating.…”

“…Mandibular splints were fabricated from impressions made of Blu-Mousse (Blu-Mousse is a fastsetting vinyl polysiloxane material produced by Parkell, Inc., 300 Executive Drive, Edgewood, NY 11717, USA) (Brugger et al, 2011;Brugger et al, 2012;Meier et al, 2014). Stainless steel electrodes were embedded in each splint at the labial and lingual centers of the left mandibular canine.…”

Tracking local anesthetic effects using a novel perceptual reference approach

“…The idea behind selecting a tooth as a target site for evoking a pure pain experience is not new (Chatrian et al, 1975) and relies on the observation that repetitive electric stimuli reliably evoke short and sharp painful sensations (A-␦-fiber-mediated pain) and no superimposed mechanosensations or thermosensations (Brügger et al, 2011(Brügger et al, , 2012Meier et al, 2014Meier et al, , 2015Närhi et al, 1992). A-␦-and C-nociceptors dominate intrinsic tooth innervation.…”

“…Mandibulary splints were fabricated from dental impressions made of Blu-Mousse [Blu-Mousse is a fast-setting vinyl polysiloxane material produced by Parkell (Edgewood, NY)] (Brügger et al, 2012;Meier et al, 2014Meier et al, , 2015. Stainless-steel electrodes were embedded into each splint at the labial and palatal centers of the left and right mandibular canine (Fig.…”

“…Its underlying psychophysical concept requires subjects to self-adjust the stimulus strength to a nonanesthetized tooth every 5 s, so that it matches the perceived intensity in an homologous tooth that received a LA injection, while perpetually stimulated with a given stimulus strength. Since electric tooth stimulation evokes reliable and stable pain perceptions (Brügger et al, 2012;Meier et al, 2014Meier et al, , 2015, we opted for this experimental model, but the current approach might be applied to other body sites.…”