Local anesthesia has made dental treatment more comfortable since 1884, but little is known about associated brain mechanisms. Functional magnetic resonance imaging is a modern neuroimaging tool widely used for investigating human brain activity related to sensory perceptions, including pain. Most brain regions that respond to experimental noxious stimuli have recently been found to react not only to nociception alone, but also to visual, auditory, and other stimuli. Thus, presumed functional attributions have come under scrutiny regarding selective pain processing in the brain. Evidently, innovative approaches are warranted to identify cerebral regions that are nociceptive specific. In this study, we aimed at circumventing known methodological confounders by applying a novel paradigm in 14 volunteers: rather than varying the intensity and thus the salience of painful stimuli, we applied repetitive noxious dental stimuli at constant intensity to the left mandibular canine. During the functional magnetic resonance imaging paradigm, we suppressed the nociceptive barrage by a mental nerve block. Brain activity before and after injection of 4% articaine was compared intraindividually on a group level. Dental pain extinction was observed to correspond to activity reduction in a discrete region of the left posterior insular cortex. These results confirm previous reports demonstrating that direct electrical stimulation of this brain region-but not of others-evokes bodily pain sensations. Hence, our investigation adds further evidence to the notion that the posterior insula plays a unique role in nociceptive processing. The human brain response to dental pain relief AbstractLocal anesthesia has made dental treatment more comfortable since 1884, but little is known about associated brain mechanisms. Functional magnetic resonance imaging (fMRI) is a modern neuroimaging tool widely used for investigating human brain activity related to sensory perceptions, including pain. Recently, most brain regions that respond to experimental noxious stimuli have been found to react not only to nociception alone, but also to visual, auditory and other stimuli. Thus, presumed functional attributions have come under scrutiny regarding selective pain processing in the brain. Evidently, innovative approaches are warranted to identify cerebral regions that are nociceptivespecific. In this study, we aimed at circumventing known methodological confounders by applying a novel paradigm in 14 volunteers: rather than varying the intensity and thus the salience of painful stimuli, we applied repetitive noxious dental stimuli at constant intensity to the left mandibular canine.During the fMRI paradigm we suppressed the nociceptive barrage by a mental nerve block. Brain activity before and after injection of 4% articaine was compared intra-individually on a group level.Dental pain extinction was observed to correspond to activity reduction in a discrete region of the left posterior insular cortex. These results confirm previous reports dem...

Ettlin DA, Lukic N, Abazi J, Widmayer S, Meier ML. Tracking local anesthetic effects using a novel perceptual reference approach. J Neurophysiol 115: 1730 -1734, 2016. First published January 20, 2016 doi:10.1152/jn.00917.2015.-Drug effects of loco-regional anesthetics are commonly measured by unidimensional pain rating scales. These scales require subjects to transform their perceptual correlates of stimulus intensities onto a visual, verbal, or numerical construct that uses a unitless cognitive reference frame. The conceptual understanding and execution of this magnitude estimation task may vary among individuals and populations. To circumvent inherent shortcomings of conventional experimental pain scales, this study used a novel perceptual reference approach to track subjective sensory perceptions during onset of an analgesic nerve block. In 34 male subjects, nociceptive electric stimuli of 1-ms duration were repetitively applied to left (target) and right (reference) mandibular canines every 5 s for 600 s, with a side latency of 1 ms. Stimulus strength to the target canine was programmed to evoke a tolerable pain intensity perception and remained constant at this level throughout the experiment. A dose of 0.6 ml of articaine 4% was submucosally injected at the left mental foramen. Subjects then reported drug effects by adjusting the stimulus strength (in milliamperes) to the reference tooth, so that the perceived intensity in the reference tooth was equi-intense to the target tooth. Pain and stimulus perception offsets were indicated by subjects. Thus, the current approach for matching the sensory experience in one anatomic location after regional anesthesia allows detailed tracking of evolving perceptual changes in another location. This novel perceptual reference approach facilitates direct and accurate quantification of analgesic effects with high temporal resolution. We propose using this method for future experimental investigations of analgesic/anesthetic drug efficacy.

Converging lines of evidence indicate that the pain experience emerges from distributed cortical nodes that share nociceptive information. While the theory of a single pain center is still not falsifiable by current neuroimaging technology, the validation of distinct brain mechanisms for acute pain and its relief is ongoing and strongly dependent on the employed experimental design. In the current study including a total of 28 subjects, a recently presented, innovative experimental approach was adopted that is able to clearly differentiate painful from non-pain perceptions without changing stimulus strength and while recording brain activity using functional magnetic resonance imaging (fMRI). Namely, we applied a repetitive and purely nociceptive stimulus to the tooth pulp with subsequent suppression of the nociceptive barrage via a regional nerve block. The study aims were 1) to replicate previous findings of acute pain demonstrating a fundamental role of the operculo-insular region and 2) to explore its functional connectivity during pain and subsequent relief. The brain activity reduction in the posterior insula (pINS) due to pain extinction was confirmed. In addition, the posterior S2 region (OP1) showed a similar activity pattern, thus confirming the relevance of the operculo-insular cortex in acute pain processing. Furthermore, the functional connectivity analysis yielded an enhanced positive coupling of the pINS with the cerebellar culmen during pain relief, whereas the OP1 demonstrated a positive coupling with the posterior midcingulate cortex during pain. The current results support the conceptual synthesis of localized specialization of pain processing with interactions across distributed neural targets.