Proton magnetic resonance spectroscopy assessment of metabolite status of the anterior cingulate cortex in chronic pain patients and healthy controls

Takahiro Ito; Sachiko Tanaka-Mizuno; Narihito Iwashita; Ikuo Tooyama; Akihiko Shiino; Katsuyuki Miura; Sei Fukui

doi:10.2147/JPR.S123403

Proton magnetic resonance spectroscopy assessment of metabolite status of the anterior cingulate cortex in chronic pain patients and healthy controls

J Pain Res. 2017 Jan 31:10:287-293. doi: 10.2147/JPR.S123403. eCollection 2017.

Authors

Takahiro Ito¹, Sachiko Tanaka-Mizuno², Narihito Iwashita³, Ikuo Tooyama⁴, Akihiko Shiino⁵, Katsuyuki Miura⁶, Sei Fukui³

Affiliations

¹ Department of Public Health, Shiga University of Medical Science.
² Department of Medical Statistics, Shiga University of Medical Science, Otsu, Japan; The Center for Data Science Education and Research, Shiga University, Hikone, Japan.
³ Department of Anesthesiology, Interdisciplinary Pain Management Center, Shiga University of Medical Science Hospital.
⁴ Molecular Neuroscience Research Center, Shiga University of Medical Science.
⁵ Biomedical MR Science Center, Shiga University of Medical Science.
⁶ Department of Public Health, Shiga University of Medical Science; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan.

Abstract

Background: Chronic pain is a common cause of reduced quality of life. Recent studies suggest that chronic pain patients have a different brain neurometabolic status to healthy people. Proton magnetic resonance spectroscopy (¹H-MRS) can determine the concentrations of metabolites in a specific region of the brain without being invasive.

Patients and methods: We recruited 56 chronic pain patients and 60 healthy controls to compare brain metabolic characteristics. The concentrations of glutamic acid (Glu), myo-inositol (Ins), N-acetylaspartate (NAA), Glu + glutamine (Glx), and creatine + phosphocreatine (total creatine [tCr]) in the anterior cingulate cortex of participants were measured using ¹H-MRS. We used age- and gender-adjusted general linear models and receiver-operating characteristic analyses for this investigation. Patients were also assessed using the Hospital Anxiety and Depression Scale (HADS) to reveal the existence of any mental health issues.

Results: Our analysis indicates that pain patients have statistically significantly higher levels of Glu/tCr (p=0.039) and Glx/tCr (p<0.001) and lower levels of NAA/tCr than controls, although this did not reach statistical significance (p=0.052). Receiver-operating characteristic analysis performed on the combination of Glx/tCr, Ins/tCr, and NAA/tCr effectively discriminated chronic pain patients from healthy controls. Patients with higher HADS-Depression scores had increased Glx/rCr levels (p=0.015), and those with higher HADS-Anxiety scores had increased NAA/tCr levels (p=0.018).

Conclusion: Chronic pain patients have a different metabolite status in the anterior cingulate cortex to controls. Within the pain patient group, HADS scores had a positive relationship with NAA/tCr and Glx/tCr levels. ¹H-MRS successfully detected metabolic changes in patients' brains in a noninvasive manner, revealing its potential as a superior diagnostic tool for pain patients.

Keywords: N-acetylaspartate; chronic pain; creatine; glutamic acid; magnetic resonance spectroscopy; myo-inositol.