We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct ‘neuroinflammatory signatures’. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. ‘radicular’ versus ‘axial’ back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of ‘fibromyalgianess’ (i.e. the degree of pain centralization, or ‘nociplastic pain’). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex–thalamus connectivity across groups. Our findings support the existence of ‘neuroinflammatory signatures’ that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

中文翻译：

---

慢性腰痛亚型的神经免疫特征

我们最近发现，患有不同慢性疼痛状况（如慢性腰痛、纤维肌痛、偏头痛和海湾战争疾病）的患者大脑和/或脊髓的胶质标志物 18-kDa 易位蛋白 (TSPO) 水平升高，这表明神经炎症可能是一种普遍现象，可在多种病因学异质性疼痛疾病中观察到。有趣的是，这种神经炎症信号的空间分布似乎表现出一定程度的疾病特异性（例如，关于初级体感皮层的参与），这表明不同的疼痛状况可能表现出不同的“神经炎症特征”。为了进一步探索这个假设，我们测试了神经炎症信号是否可以根据临床表现表征慢性腰痛患者的假定病因亚型。具体来说，我们探讨了慢性腰痛患者的神经炎症是否放射到腿部或未放射到腿部（即“根性”与“轴向”背痛）。54 名慢性腰痛患者，26 名轴向腰痛 [43.7 ± 16.6 岁（平均值 ± SD）] 和 28 名患有根性背痛（48.3 ± 13.2 岁）的患者接受了 11C-PBR28 的 PET/MRI，用于 TSPO 的第二代放射性配体。11C-PBR28 信号使用标准化摄取值比率进行量化（根据分布体积比验证；n = 23）。功能性 MRI 数据与 11C-PBR28 数据同时收集 (i) 以功能定位初级体感皮层背部和腿部亚区；(ii) 进行功能连接分析（以研究神经炎症信号可能的神经生理学相关性）。PET 和功能性 MRI 测量在各组之间进行了比较，相互关联，并与“纤维肌痛”的严重程度（即疼痛集中程度或“痛性疼痛”）相互关联。此外，统计中介模型被用来探索这三个变量之间可能的因果关系。对于背部/腿部的初级躯体感觉皮层表示，11C-PBR28 PET 信号和丘脑的功能连接是：（i）与轴向背痛患者相比，神经根更高；(ii) 彼此正相关；(iii) 与各组的纤维肌痛评分呈正相关；最后（iv）纤维肌痛介导了 11C-PBR28 PET 信号与各组初级体感皮层-丘脑连接之间的关联。我们的研究结果支持存在伴随神经生理学变化并与慢性疼痛患者的临床表现（特别是疼痛程度）相关的“神经炎症特征”。这些特征可能有助于对不同的疼痛综合征进行亚型分类，并提供有关诊断组内神经免疫脑信号的个体间变异性的信息，这些信息最终可能成为基于机制的精准医学方法的目标。我们的研究结果支持存在伴随神经生理学变化并与慢性疼痛患者的临床表现（特别是疼痛程度）相关的“神经炎症特征”。这些特征可能有助于对不同的疼痛综合征进行亚型分类，并提供有关诊断组内神经免疫脑信号的个体间变异性的信息，这些信息最终可能成为基于机制的精准医学方法的目标。我们的研究结果支持存在伴随神经生理学变化并与慢性疼痛患者的临床表现（特别是疼痛程度）相关的“神经炎症特征”。这些特征可能有助于对不同的疼痛综合征进行亚型分类，并提供有关诊断组内神经免疫脑信号的个体间变异性的信息，这些信息最终可能成为基于机制的精准医学方法的目标。