| Summary: | Background: Pain in osteoarthritis (OA) primarily results from tissue damage but its' intensity does not essentially parallel the extent of joint destruction or presence of active inflammation, thus suggesting the likely involvement of a central component. The mid-anterior cingulate cortex (mACC) has an important role in pain perception, intensity and progression. In OA, low mACC γ-aminobutyric acid (GABA) was associated with high pain suggesting a role of prefrontal disinhibition. Aim of the work: To investigate the role of mACC (GABA) levels in chronic knee OA (KOA) pain and determine if magnetic resonance spectroscopy (MRS) brain neurotransmitters can serve as potential biomarkers. Patients and methods: Forty-five patients with primary KOA (M/F:33/12; age:57 ± 6 years) along with 15 matched controls were recruited. Pain was assessed using Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS) and Western Ontario McMaster Osteoarthritis (WOMAC) questionnaire. mACC (GABA) was assessed and brain MRS neurotransmitters analysed including glutamate (Glx); N-acetylaspartate (NAA), total choline (tCho) and myo-inositol. Results: MRS analysis demonstrated no metabolite differences between controls and KOA patients in GABA, Glx, NAA and tCho. Myo-inositol:Glx ratio was significantly higher in patients (1.47 ± 0.37 vs 1.1 ± 0.29; p < 0.001). mACC (GABA) negatively correlated with VAS (r = −0.86, p < 0001), PCS (r = −0.94, p < 0001) and WOMAC (r = −0.96, p < 0001) in KOA patients. Myo-inositol:Glx significantly correlated with the age (r = 0.31, p < 0.038), disease duration (r = 0.61, p < 0.0001), VAS (r = 0.4, p < 0.02), PCS (r = 0.48, p < 0.001) and WOMAC (r = 0.53, p < 0.0001). Conclusions: This work confirms the importance of mACC in central sensitization of pain and highlights a promising role of the inflammatory neurotransmitter GABA and myo-inositol:Glx ratio as mechanistic biomarkers of chronic KOA pain. Keywords: Knee osteoarthritis, Pain, Magnetic resonance spectroscopy, Brain biomarkers
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