Distinct Brain Mechanisms Related to Dental Pain Relief

Objectives: Local anesthesia has made life more comfortable for dental patients since 1884. However, little is known about brain mechanisms related to dental pain relief. The aim of this study was to investigate 1) task related brain activity and 2) functional connectivity patterns following onset of a regional anesthetic nerve block during continuous noxious dental stimulation.

Methods: For this placebo-controlled and age-matched fMRI study a total of 28 subjects were included (only males, mean age = 27.09, SD ±7.06). Repetitive electric stimuli evoking an intensity perception of 5 on an 11-point NRS were applied to the left mandibular canine. The experiment was divided into two phases: Phase 1 (30 stimuli; duration 5 min) was followed by a submucosal injection of the anaesthetic articaine 4% (group A) or 0.9% NaCl as placebo (group P) at the left mental foramen. Electric tooth stimulation continued for 16 min (phase 2) during which subjects indicated pain offset by pressing an alarm ball. Task-related activation and connectivity analysis was performed using SPM8 and context-dependent psychophysical interactions (PPI).

Results: In group A, pain relief was reported 4.5 min (SD = 5.1 min) after the injection whereas in group P, no subject reported pain relief. Between-group analysis of phase 2 demonstrated a significant activation cluster in the ipsilateral posterior insula (pIns) in group P (p<0.02, FWE-corrected). Using the pIns as a seed region the PPI analysis yielded a significant enhanced coupling to the midbrain (periaqueductal grey / ventral tegmental area) after analgesia onset in group A only (p < 0.005, FWE-corrected).
Conclusions: The novel paradigm applied in this study demonstrated that dental pain relief was accompanied by a significant activity reduction in the posterior insula and an enhanced connectivity to the midbrain. Our data suggest a distinct role of these brain regions in dental pain and its relief.