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山东省立医院疼痛科英语晨读已经坚持10余年的时间了，每天交班前15分钟都会精选一篇英文文献进行阅读和翻译。一是可以保持工作后的英语阅读习惯，二是可以学习前沿的疼痛相关知识。我们会将晨读内容与大家分享，助力疼痛学习。
本次文献选自Francesca Guidaa，Monica Iannottaa，Gabriella Misso, et al. Pain. 2022.本次学习由李芸主治医师主讲。
The huge upregulation of CD38 (15.4-fold), also found in the 12-month sham mice compared with the 1-month sham animals, suggests a possible aging-related accumulation of M1 polarized macrophage and NAD decrease. We found an increased expression of CCR2, the specific CCL2 (MCP-1) chemokine receptor, previously shown to crucially participate in the chronic pain development and to colocalize with either dopaminergic or cholinergic neurons in different brain regions where it modulates extravasation and migration of monocytes to the inflammatory sites. The substantial upregulation of macrophage colony-stimulating factor-1 suggests an increased susceptibility of mononuclear phagocytes to ECM proteins' stimulation and their consequent activation, which is associated with postinjury regeneration rather than with a mere proinflammatory function. Worthy of note was also the relevant increase of transferrin-bound iron uptake, as demonstrated by the huge induction of transferrin receptor TFRC, as a metabolic reorganization after injury. Such substantial modifications were not detectable in the 12-month SNI mice. These findings may be in agreement with the partial restoration of the behavioral (and electrophysiological) phenotype. However, the flattening in the neuroinflammatory mediators in the 12-month SNI mice could also be masked by the increased basal levels of those molecules in the matched-aged sham mice. Concerning the PFC, we found that only Tbx21 in the 1-month SNI mice, and Ctla4 and Vcam in the 12-month SNI mice reached the significance, among the nearly 50 deregulated genes. Worth mentioning, a detailed analysis of differential DNA methylation in the PFC of SNI mice, performed by Topham et al., revealed an interesting time specific CpG methylation dynamics. Although not including any of the 3 deregulated PFC genes identified in our study, the observed methylation profile could fairly imply a functional outcome similar to the one postulated on the bases of our findings, as denoted by gene ontology analysis. Indeed, throughout the time course, authors observed a specific enrichment in genes implicated in inflammatory and T-cell adaptive immune responses, including Toll receptor signaling pathway, as well as an involvement of a series of adhesion molecules. Overall, these findings suggest a functional connection with the genes discussed in this study.
12个月对照组小鼠，与1个月的对照组小鼠相比，CD38的表达明显上调，表明M1型极化巨噬细胞（促炎作用）和辅酶NAD的减少可能与衰老有关。我们发现CCR2（特异性CCL2 （MCP-1）趋化因子受体）的表达增加，之前的研究表明CCR2在慢性疼痛的发展中至关重要，并与不同大脑区域的多巴胺能或胆碱能神经元共定位，它调节单核细胞向炎症部位的迁移。巨噬细胞集落刺激因子-1的大量上调表明单核吞噬细胞对ECM蛋白的刺激和随后的激活的敏感性增加，这不仅是简单的促炎功能，可能与神经损伤后再生有关。值得注意的是，转铁蛋白受体TFRC诱导的转铁蛋白结合铁摄入量的相关增加，是一种损伤后的代谢重组。但在SNI后12个月小鼠中没有检测到这种改变。这些结果可能与行为学（和电生理学）表型的部分恢复相一致。然而，相应年龄的对照组小鼠神经炎症介质基础水平的增加可能会掩盖SNI后12个月小鼠这些因子的变化。关于PFC，研究发现在近50个失调基因中，SNI 1个月小鼠中只有Tbx21表达有显著差异，在SNI12个月小鼠Ctla4和Vcam表达有显著差异。值得一提的是，Topham等人对SNI小鼠PFC中差异DNA甲基化进行了详细分析，发现时间特异性CpG甲基化动力学。尽管甲基化的基因不包括该研究中发现的3个失调PFC基因中的任何一个，但观察到的甲基化提示我们可能是基于我们研究发现的功能改变。在整个研究过程中，作者证实了神经病理性疼痛过程有与炎症和T细胞适应性免疫反应有关的基因的特定富集，包括Toll受体信号通路，以及一系列粘附分子的参与。总的来说，这些发现表明了与本研究中讨论的基因的功能联系。
5. Limits
First, our analysis does not include the 1-year response to SNI by female sex. This remains an important issue, given also the role of immune cells in the sex differences in pain processing. Second, gene expression analyses have been performed on tissue samples derived from whole PFC and hippocampus homogenates instead of specific subregions. Thus, we cannot exclude that some signal differences may be diluted. Third, we suggest the involvement of molecular pathways (Fig. S2, available at http://links.lww.com/PAIN/B547) in the SNI phenotype, but no molecular mechanism has been investigated. We recognize these limitations, and we propose our findings as a first step towards understanding functional changes associated with long term neuropathic pain.
5.局限性
首先，我们的分析不包括性别对SNI后12个月小鼠的影响。考虑到免疫细胞在疼痛处理过程中有性别差异，这可能是一个比较重要的问题。第二，基因表达分析组织来源是整个PFC和海马，而不是特定的亚区。因此，我们不能排除一些有意义的基因表达差异可能被稀释。第三，我们认为SNI表型涉及分子途径但尚未对分子机制进行研究。在后续关于长期神经性疼痛相关的功能改变的研究中，要解决这些问题。
6. Conclusions
Our data indicate that the 1-year SNI condition is not associated with cognitive impairments, suggesting that distinct brain circuits may drive the psychiatric components of neuropathic pain. Moreover, this study suggests that hippocampal neuroinflammation may influence the development of affective feature of neuropathic pain. This study paves the way for better in vestigation of the long-term consequences of peripheral nerve injury in which most of the available drugs are to date unsatisfactory.
6.结论
我们的数据表明，SNI后12 个月小鼠存在疼痛和抑郁样行为，而认知障碍基本恢复，这表明负责神经病理性疼痛的疼痛成分和精神成分可能是不同的脑区。此外，本研究提示海马神经炎症可能影响神经病理性疼痛情绪成分的发展。这项发现为以后研究周围神经损伤的远期损害奠定了基础。
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