英語晨讀 ·
山東省立醫(yī)院疼痛科英語晨讀已經(jīng)堅持10余年的時間了，每天交班前15分鐘都會精選一篇英文文獻(xiàn)進(jìn)行閱讀和翻譯。一是可以保持工作后的英語閱讀習(xí)慣，二是可以學(xué)習(xí)前沿的疼痛相關(guān)知識。我們會將晨讀內(nèi)容與大家分享，助力疼痛學(xué)習(xí)。
本次文獻(xiàn)選自Francesca Guidaa，Monica Iannottaa，Gabriella Misso, et al. Pain. 2022.本次學(xué)習(xí)由李蕓主治醫(yī)師主講。
We showed that spatial and discriminative memory was not impaired in the 12-month SNI mice, along with the physiological establishment of the hippocampal LTP. In the same animals, extracellular glutamate levels were unchanged, whereas gamma aminobutyric acid (GABA) levels resulted increased. These neurobiochemical data suggest that in the 12-month SNI mice, the oversensitization due to the glutamate spillover may be counterbalanced by an increased activity of the GABAergic terminals.
研究發(fā)現(xiàn)，12個月SNI組小鼠的空間記憶和辨別記憶基本恢復(fù)正常，海馬LTP也基本恢復(fù)。細(xì)胞外谷氨酸水平?jīng)]有變化，而GABA水平升高。神經(jīng)生化數(shù)據(jù)表明，在12個月SNI小鼠中，由于谷氨酸溢出導(dǎo)致的高敏狀態(tài)可能被GABA活性的增加所抵消。
Specifically, we tested the effects of SNI on the pattern separation during the NOR test using similar or substantially dissimilar objects. Thirty-day injured mice exhibited recognition deficits, as shown by the disruption of NOR memory. This effect was not dependent on the relative similarity of the tested objects (pattern separation or NOR), indicating that SNI mice were not able to remember the shape of the objects they have seen the day before. On the contrary, the 12-month SNI mice showed a regular NOR and an unaltered spatial memory. These findings strengthen the concept that the disruption of LEC-DG circuitry may contribute, at least partly, to the cognitive impact of neuropathic pain. Of interest, the 12-month SNI mice showed an impaired pattern separation. It should be taken into account that pattern separation performances may gradually decline with the aging. Through multiple mechanisms mainly in the DG and CA3 regions, separation performances have been correlated with adult DG neurogenesis. It is known that the production of new DG neurons markedly decreases with age. Thus, we cannot rule out that 1 year of SNI may worse the age-associated deficits or, alternatively, may negatively affect other structures regulating pattern separation ability in aged animals, ie, perirhinal cortex.
NOR測試中采用完全不同或相似的物體檢測SNI對小鼠識別能力的影響。神經(jīng)損傷后1個月小鼠出現(xiàn)識別障礙，表現(xiàn)為NOR記憶的紊亂。但SNI后12個月小鼠表現(xiàn)出正常的NOR和空間記憶能力。這些發(fā)現(xiàn)說明，LEC-DG的破壞可能至少部分地影響了神經(jīng)病理性疼痛的認(rèn)知能力。同時還應(yīng)考慮到辨別能力的下降有一部分原因是衰老。區(qū)分性能與成人DG神經(jīng)功能相關(guān)，而新生DG神經(jīng)元的產(chǎn)生隨著年齡的增長而顯著減少。因此，我們不能排除SNI后12個月可能是衰老加重了相關(guān)的缺陷，或者可能是衰老影響到了負(fù)責(zé)辨別能力的其他結(jié)構(gòu)（比如皮層）。
It is known that reward circuitry components participate in depression and chronic pain mechanisms. Indeed, stimulation of NAc has been correlated with the reduction of depressive symptoms of chronic pain. In this study, we observed that both the 1-month and 12-month SNI mice showed impaired LTP in PFC-Nacore pathway. These data are compatible with recent findings showing that the deactivation of PFC-Nacore projection in rats induces an exacerbation of both sensory and aversive phenotypes of SNI. Thus, we can speculate that the reduced synaptic plasticity in the PL projection to the NAcore may play a role in the affective consequences of SNI.
眾所周知，獎賞機(jī)制可能參與抑郁和慢性疼痛的發(fā)生。刺激NAc可以緩解慢性疼痛相關(guān)的抑郁癥狀。本研究發(fā)現(xiàn)SNI后 1個月和12個月小鼠在PFC-Nacore信號通路中均出現(xiàn)LTP受損。這些數(shù)據(jù)與最近的研究結(jié)果一致，即小鼠PFC-Nacore信號通路失活可導(dǎo)致SNI感覺和厭惡表型的加重。因此，我們推測，PFC投射到Nacore信號通路的突觸可塑性降低可能在SNI的負(fù)面情緒中發(fā)揮作用。
The immune system is deeply involved in neuropathic pain pathophysiology. Previous studies suggested that the immune-neuronal communication initiated by proinflammatory mediators may participate to the sensorial components, as well as the affective components of neuropathic pain. Specifically, neuroinflammation, driven by changes in resident microglia and astrocytes, triggers neural reorganization believed to be responsible for cognitive deficit and depression after peripheral nerve injury. In addition, depending on the nature of injury, T cells may contribute to the onset or the resolution of pain. Regarding the SNI model, while Costigan et al. have suggested the role of peripheral T cells in the spinal pain processing, another study indicated that there is not a relevant T-cell infiltration. Our data indicate that 1 or 12 months of SNI does not affect the percentage of circulating regulatory T cells. However, further analysis is needed to evaluate the possible T-cell infiltration into the brain parenchyma to exclude their recruitment in an earlier stage and the consequent possible interaction with the resident immune cells. Despite the absence of a significant blood Tregs participation, we found changes in immune-related gene expression in the hippocampus in response to SNI. Of interest, in the 1-month neuropathic mice, but not in the 12-month neuropathic mice, we detected an enhancement of several genes, most of them involved in inflammation and apoptosis signaling pathways. We found an increased expression of IL-1b together with an upregulation of other substrates, such as Nf-Kb, C3, CD38, CD68, and Socs2, widely recognized as markers of neuroinflammation, brain damage, and aging. Therefore, we described the dysregulation of a number of immunomodulatory molecules, suggesting a hippocampal neuroinflammatory response, which may contribute to the SNI phenotype. Besides the immunoregulatory activity, IL-1β can negatively regulate hippocampal synaptic plasticity. Thus, we cannot exclude that increase of IL-1β may be, at least partly, responsible for impaired LTP in the 1-month SNI mice by compromising memory and learning processes.
免疫系統(tǒng)與神經(jīng)病理性疼痛的病理生理學(xué)密切相關(guān)。以往的研究證實，促炎介質(zhì)啟動的免疫-神經(jīng)元溝通可能參與神經(jīng)病理性疼痛的感覺成分和情緒成分。由固有小膠質(zhì)細(xì)胞和星形膠質(zhì)細(xì)胞的變化驅(qū)動的神經(jīng)炎癥，觸發(fā)神經(jīng)元重組，該過程被認(rèn)為誘發(fā)周圍神經(jīng)損傷后認(rèn)知缺陷和抑郁的發(fā)生。此外，根據(jù)損傷的性質(zhì)，T細(xì)胞可能有助于疼痛的發(fā)生或緩解。我們的數(shù)據(jù)顯示，SNI 1個月或12個月不會影響調(diào)節(jié)性T細(xì)胞的百分比，但是海馬中免疫相關(guān)基因表達(dá)發(fā)生變化，即在SNI后1個月的小鼠中，檢測到參與炎癥和凋亡信號通路基因的表達(dá)增強(qiáng)，而SNI后12個月沒有該變化。此外IL-1β表達(dá)增加，同時伴有與神經(jīng)炎癥、腦損傷和衰老高度相關(guān)的其他底物（如NF-кb、C3、CD38、CD68和Socs2）的表達(dá)上調(diào)。因此，我們不能排除IL-1β的增加，可能至少部分地，通過損害記憶和學(xué)習(xí)過程，影響了 SNI后1個月小鼠LTP。
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