Dental Pain induced Neurochemical Changes in the Human Trigeminal Brainstem

Objectives: Magnetic resonance spectroscopy (MRS) based research revealed neurochemical alterations in response to pain in cortical areas such as the anterior/posterior insula, cingulate subdivisions and thalamus. Only vague ideas exist regarding pain related neurochemical changes in a crucial relay area: the brainstem. This pilot study aimed at analyzing neurochemical alterations within the human brainstem's trigeminal complex by means of an established experimental dental pain paradigm.
Methods: 18 healthy male volunteers (aged 19-42), unaffected by psychiatric, neurologic or pain related problems participated. All received detailed information about the nature of the study which was approved by the local ethics committee.
An individual dental splint with embedded electrodes was fabricated for electric stimulation of the maxillary right canine. Sensory detection and pain thresholds were carefully determined with a focus on evoking moderate pain equal to 5 on a numeric 11-point pain scale.
MR experiments were performed on a 3 Tesla Philips Achieva scanner (Philips Healthcare, Best, the Netherlands). High-resolution T2-weighted images in axial and sagittal orientations were acquired to ensure precise voxel planning and positioning, covering the right trigeminal brainstem complex.
In a first run, the neurochemical baseline was determined without stimulation. The second run was accompanied by painful stimulation of the canine tooth. The whole MR experiment lasted approximately one hour. SPSS 22 was used to perform statistical analysis, significance was set at p < 0.05.
Results: Comparing baseline vs. stimulation, following neurochemical compounds demonstrated a significant drop under pain stimulation (p<0.05): N-Acetylaspartate (tNAA), creatine (Cre), choline (tCho) and gamma-aminobutric acid (GABA). Glutamate (Glu) and the combination of Glu and glutamine (Glx) demonstrated a trend in the same direction with p=0.078 and p=0.12, respectively.
Conclusions: This pilot study revealed for the first time that several neurochemical compounds in the human brainstem's trigeminal complex are significantly altered during experimentally induced dental pain.