Brain gamma-aminobutyric acid, but not glutamine and glutamate levels are lower in older adults with chronic musculoskeletal pain: considerations by sex and brain location

Introduction and Objectives: GABAergic and glutamatergic neurotransmitter systems are central to the pathophysiology of chronic pain and are equally affected by aging processes. We measured levels of frontal gamma-aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) in vivo using proton magnetic resonance spectroscopy (H-1-MRS) to elucidate age-specific and pain-specific associations with clinical and experimental pain in older adults. Methods: Younger (18-24, n = 24) and older (60-94, n = 41) individuals part of a larger study (Neuromodulatory Examination of Pain and Mobility Across the Lifespan [NEPAL]) underwent questionnaires, quantitative sensory testing, and H-1-MRS Mescher-Garwood point-resolved spectroscopy to measure GABA and Glx levels in prefrontal and sensorimotor brain regions. Results: Older participants had significantly lower sensorimotor, but not prefrontal, GABA and Glx levels, compared with younger controls (P's < 0.05). Younger controls had significantly higher prefrontal and sensorimotor GABA, but not Glx, levels compared with older controls and older adults with chronic pain (P's < 0.05). Older males with chronic pain had significantly lower prefrontal GABA compared with older and younger male controls (P's < 0.05). Prefrontal GABA, but not Glx, was significantly associated with self-reported and experimental pain measures (P's < 0.05). Our results are the first to focus exclusively on age and pain differences in GABA and Glx including younger and older controls to elucidate aging and pain contributions to brain GABAergic and glutamatergic processes. Conclusion: Evaluation of both the neuroinhibitory and neuroexcitatory mechanisms provide promising potential for improving both our understanding of the mechanisms of chronic pain in aging and opportunities for effective, individualized treatments.