Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats.
Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats.
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DOI：
10.1007/s12035-021-02447-1
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发表时间：
2021-10
影响因子：
5.1
通讯作者：
Rauhala PV
中科院分区：
文献类型：
--
作者：
Ahlström FHG;Mätlik K;Viisanen H;Blomqvist KJ;Liu X;Lilius TO;Sidorova Y;Kalso EA;Rauhala PV
神经性疼痛在女性中更为普遍。然而，女性在动物实验中的代表性不足，性别差异的机制仍然没有得到充分的理解。我们在大鼠中使用备用神经损伤（SNI）模型来表征疼痛行为的性别差异，无偏见的RNA-Seq和蛋白质组学来研究机制。对雄性和雌性大鼠进行SNI和假手术。机械和冷异常性疼痛进行了评估。在第7天收集同侧腰背根神经节（DRG）和脊髓（SC）节段用于用DESeq 2进行RNA-seq分析。在第21天采集用于蛋白质组学分析的脑脊液（CSF）样品以及分别用于IB-4和CGRP以及IBA 1和GFAP分析的DRG和SC。雌性出现更强的机械性异常性疼痛。在DRG中的CGRP和IB-4或SC中的神经胶质细胞标记物中，性别之间没有差异。DRG和SC的基因表达有丰富的变化。在与T细胞（cd 28、ctla 4、cd 274、cd 4、prf 1）、其他免疫反应（dpp 4、c5 a、cxcr 2和il 1b）、神经传递（hrh 3、thbs 4、chrna 4和pdyn）、可塑性（atf 3、c1 qc和reg 3b）以及其他（bhlhe 22、mcpt 1 l、trpv 6）相关的基因中发现了性二态反应。我们观察到雌性大鼠的机械性异常性疼痛明显更强，并且大鼠SNI后基因表达出现许多性二态变化。一些基因先前已被链接到NP，而一些是新的。我们的研究结果表明，在开发新的，可能是性别特异性的，治疗NP的进一步研究的基因靶点。在线版本包含补充材料，可通过10.1007/s12035-021-02447-1获取。
Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP. The online version contains supplementary material available at 10.1007/s12035-021-02447-1.
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影响因子：
5.3
作者：
Cao, De-Li;Zhang, Zhi-Jun;Xie, Rou-Gang;Jiang, Bao-Chun;Ji, Ru-Rong;Gao, Yong-Jing
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Gao, Yong-Jing
影响因子：
3.6
作者：
Chaumette, T.;Chapuy, E.;Sors, A.
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影响因子：
4.3
作者：
GORRELL, MD;WICKSON, J;MCCAUGHAN, GW
通讯作者：
MCCAUGHAN, GW
DOI：
10.1523/jneurosci.4569-09.2009
发表时间：
2009-11-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Costigan M;Moss A;Latremoliere A;Johnston C;Verma-Gandhu M;Herbert TA;Barrett L;Brenner GJ;Vardeh D;Woolf CJ;Fitzgerald M
通讯作者：
Fitzgerald M
影响因子：
7
作者：
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通讯作者：
Romero, Roberto