Neurometabolite Levels and Relevance to Central Sensitization in Chronic Orofacial Pain Patients: A Magnetic Resonance Spectroscopy Study

Makoto Terumitsu; Yuhei Takado; Ken-Ichi Fukuda; Eisuke Kato; Sei Tanaka

doi:10.2147/JPR.S362793

Neurometabolite Levels and Relevance to Central Sensitization in Chronic Orofacial Pain Patients: A Magnetic Resonance Spectroscopy Study

J Pain Res. 2022 May 16:15:1421-1432. doi: 10.2147/JPR.S362793. eCollection 2022.

Authors

Makoto Terumitsu^{1

2}, Yuhei Takado³, Ken-Ichi Fukuda², Eisuke Kato², Sei Tanaka⁴

Affiliations

¹ Division of Dental Anesthesiology, Department of Human Biology and Pathophysiology, Health Sciences University of Hokkaido, Hokkaido, Japan.
² Division of Special Needs Dentistry and Orofacial Pain, Department of Oral Health and Clinical Science, Tokyo Dental College, Tokyo, Japan.
³ Department of Functional Brain Imaging, Institute of Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, Japan.
⁴ Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo, Japan.

Abstract

Background: Refractory chronic pain in the orofacial region involves central sensitization (CS). However, not all chronic pain patients exhibit CS. An objective assessment of CS may be useful for pain management. Changes in the balance of excitatory and inhibitory neural activity or excessive activity of nerves and glial cells may cause CS and contribute to pain chronification.

Patients and methods: ¹H-magnetic resonance spectra were acquired from the anterior cingulate cortex (ACC) and thalamus in 20 patients with chronic orofacial pain and suspected CS, and 21 healthy volunteers, using a single-voxel point-resolved spectroscopy sequence. The patients were assessed using the Central Sensitization Inventory.

Results: Aspartate/total creatine (tCr) and glutathione in the ACC were significantly higher in the patient group. However, no significant difference was observed between groups in the neurometabolites measured in the thalamus. Patients also exhibited a tendency for increased gamma-aminobutyric acid (GABA)/tCr in the ACC. There were positive relationships between Central Sensitization Inventory scores and glutamate + glutamine (Glx) in the thalamus, a positive trend for Glx in the ACC and a negative relationship for GABA/tCr in the ACC.

Conclusion: The high levels of aspartate/tCr and glutathione in the patient group suggest excitatory neuronal activity and hyperactivity of neurons and glial cells. The correlation analysis results suggest that excitatory and inhibitory neurometabolites are involved in the chronification of orofacial pain, including CS.

Keywords: Central Sensitization Inventory; anterior cingulate cortex; central sensitization; magnetic resonance spectroscopy; orofacial pain; thalamus.