Valdes-Hernandez Pedro A, Montesino-Goicolea Soamy, Laffitte Nodarse Chavier, Johnson Alisa J, Fillingim Roger B, Cruz-Almeida Yenisel
Department of Community Dentistry and Behavioral Science, University of Florida, USA; Pain Research and Intervention Center of Excellence, University of Florida, USA; Center for Cognitive Aging and Memory, McKnight Brain Institute, University of Florida, USA.
Department of Community Dentistry and Behavioral Science, University of Florida, USA; Pain Research and Intervention Center of Excellence, University of Florida, USA.
J Pain. 2025 May;30:105356. doi: 10.1016/j.jpain.2025.105356. Epub 2025 Mar 1.
The brain is key in the pain-sleep relationship, and sleep is needed for glymphatic clearance. However, no studies have examined how pain relates to the glymphatic system (GS). Characterizing the GS alongside sleep quality in well-characterized pain samples is essential for advancing this understanding. Non-invasive MRI techniques, such as Diffusion Tensor Imaging-Analysis aLong the Perivascular Space (DTI-ALPS), are particularly valuable as they are approved for humans. Although the relationship between the DTI-ALPS index and the GS is primarily deductive, the index may be a proxy for waste clearance capacity in deep white matter. Its sensitivity to interstitial space changes-known to be modulated by norepinephrine-offers a unique opportunity to investigate how sleep impairment and chronic pain regulation affect specific components of brain waste clearance. We thus fitted two longitudinal models linking pain, sleep quality and the DTI-ALPS index. We hypothesized that variations in pain characteristics would predict DTI-ALPS index changes, either directly or mediated by sleep quality changes. Alternatively, we hypothesized that variations in sleep quality would predict changes in pain characteristics via DTI-ALPS index modifications. Knee pain participants (n=87) completed an MRI and self-reported measures of pain and sleep impairment at baseline and two years later. We only found evidence supporting that more widespread and longer pain at baseline significantly influenced decreases in the DTI-ALPS index in the left hemisphere through increased sleep impairment two years later (p=0.039, corrected). PERSPECTIVE: Findings highlight the need for research on the relationship between pain and sleep quality and its implications for brain health.
大脑在疼痛与睡眠的关系中起着关键作用，而类淋巴系统清除需要睡眠。然而，尚无研究探讨疼痛与类淋巴系统（GS）之间的关系。在特征明确的疼痛样本中，将类淋巴系统与睡眠质量一同进行表征，对于深化这一认识至关重要。非侵入性MRI技术，如沿血管周围间隙的扩散张量成像分析（DTI-ALPS），因其已获人体应用批准而具有特殊价值。尽管DTI-ALPS指数与类淋巴系统之间的关系主要是推断性的，但该指数可能是深部白质中废物清除能力的一个替代指标。其对已知受去甲肾上腺素调节的间质空间变化的敏感性，为研究睡眠障碍和慢性疼痛调节如何影响脑废物清除的特定成分提供了独特机会。因此，我们拟合了两个纵向模型，将疼痛、睡眠质量和DTI-ALPS指数联系起来。我们假设疼痛特征的变化将直接或通过睡眠质量变化介导来预测DTI-ALPS指数的变化。或者，我们假设睡眠质量的变化将通过DTI-ALPS指数的改变来预测疼痛特征的变化。膝关节疼痛参与者（n=87）在基线和两年后完成了MRI以及疼痛和睡眠障碍的自我报告测量。我们仅发现有证据支持，基线时更广泛、持续时间更长的疼痛通过两年后睡眠障碍的增加，显著影响左半球DTI-ALPS指数的降低（p=0.039，校正后）。观点：研究结果凸显了对疼痛与睡眠质量之间关系及其对脑健康影响进行研究的必要性。
