Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA; Diagnostic Neuroimaging Laboratory, Huntsman Mental Health Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA; Diagnostic Neuroimaging Laboratory, Huntsman Mental Health Institute, University of Utah School of Medicine, Salt Lake City, UT, USA; George E. Wahlen Department of Veterans Affairs Medical Center, VISN 19 Mental Illness Research, Education and Clinical Center, Salt Lake City, UT, USA.
Brain Behav Immun. 2024 Aug;120:1-9. doi: 10.1016/j.bbi.2024.05.020. Epub 2024 May 19.
Aberrant neuronal excitability in the anterior cingulate cortex (ACC) is implicated in cognitive and affective pain processing. Such excitability may be amplified by activated circulating immune cells, including T lymphocytes, that interact with the central nervous system. Here, we conducted a study of individuals with chronic pain using magnetic resonance spectroscopy (MRS) to investigate the clinical evidence for the interaction between peripheral immune activation and prefrontal excitatory-inhibitory imbalance. In thirty individuals with chronic musculoskeletal pain, we assessed markers of peripheral immune activation, including soluble interleukin-2 receptor alpha chain (sCD25) levels, as well as brain metabolites, including Glx (glutamate + glutamine) to GABA+ (γ-aminobutyric acid + macromolecules/homocarnosine) ratio in the ACC. We found that the circulating level of sCD25 was associated with prefrontal Glx/GABA+. Greater prefrontal Glx/GABA+ was associated with higher pain catastrophizing, evaluative pain ratings, and anxiodepressive symptoms. Further, the interaction effect of sCD25 and prefrontal Glx/GABA+ on pain catastrophizing was significant, indicating the joint association of these two markers with pain catastrophizing. Our results provide the first evidence suggesting that peripheral T cellular activation, as reflected by elevated circulating sCD25 levels, may be linked to prefrontal excitatory-inhibitory imbalance in individuals with chronic pain. The interaction between these two systems may play a role as a potential mechanism underlying pain catastrophizing. Further prospective and treatment studies are needed to elucidate the specific role of the immune and brain interaction in pain catastrophizing.
前扣带皮层（ACC）中的异常神经元兴奋性与认知和情感疼痛处理有关。这种兴奋性可能会被激活的循环免疫细胞放大，包括与中枢神经系统相互作用的 T 淋巴细胞。在这里，我们使用磁共振波谱（MRS）对慢性疼痛患者进行了一项研究，以调查外周免疫激活与前额叶兴奋-抑制失衡之间相互作用的临床证据。在 30 名患有慢性肌肉骨骼疼痛的患者中，我们评估了外周免疫激活的标志物，包括可溶性白细胞介素 2 受体α链（sCD25）水平，以及大脑代谢物，包括 ACC 中的 Glx（谷氨酸+谷氨酰胺）到 GABA+（γ-氨基丁酸+大分子/同型瓜氨酸）的比值。我们发现，循环 sCD25 水平与前额叶 Glx/GABA+有关。前额叶 Glx/GABA+越高，与更高的疼痛灾难化、评估性疼痛评分和焦虑抑郁症状有关。此外，sCD25 和前额叶 Glx/GABA+对疼痛灾难化的交互作用是显著的，表明这两个标志物与疼痛灾难化的联合关联。我们的研究结果首次提供了证据，表明外周 T 细胞激活，如升高的循环 sCD25 水平所反映的那样，可能与慢性疼痛患者的前额叶兴奋-抑制失衡有关。这两个系统之间的相互作用可能作为疼痛灾难化的潜在机制发挥作用。需要进一步的前瞻性和治疗研究来阐明免疫和大脑相互作用在疼痛灾难化中的具体作用。
