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

Takahiro Ito,1 Sachiko Tanaka-Mizuno,2,3 Narihito Iwashita,4 Ikuo Tooyama,5 Akihiko Shiino,6 Katsuyuki Miura,1,7 Sei Fukui4 1Department of Public Health, Shiga University of Medical Science, 2Department of Medical Statistics, Shiga University of Medical Science, Otsu, Japan; 3The Center for Data Science Education and Research, Shiga University, Hikone, Japan; 4Department of Anesthesiology, Interdisciplinary Pain Management Center, Shiga University of Medical Science Hospital, 5Molecular Neuroscience Research Center, Shiga University of Medical Science, 6Biomedical MR Science Center, Shiga University of Medical Science, 7Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan 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: chronic pain, magnetic resonance spectroscopy, glutamic acid, myo-inositol, N-acetylaspartate, creatine&nbsp