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T细胞死亡相关基因8介导的不同信号通路调节神经性疼痛的早期和晚期阶段。

T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain.

作者信息

Dai Shih-Ping, Yang Chun-Chieh, Chin Yin, Sun Wei-Hsin

机构信息

Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.

出版信息

iScience. 2024 Sep 13;27(10):110955. doi: 10.1016/j.isci.2024.110955. eCollection 2024 Oct 18.

DOI:10.1016/j.isci.2024.110955
PMID:39381739
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11460492/
Abstract

Peripheral nerve injury alters the transduction of nociceptive signaling. The coordination of neurons, glia, and immune cells results in persistent pain and inflammation. T cell death-associated gene 8 (TDAG8), located at nociceptors and immune cells, is involved in inflammatory pain and arthritis-induced pain. Here, we employed TDAG8-deficient mice, pharmacological approaches, and calcium/sodium imaging to elucidate how TDAG8-mediated signaling modulates neuron activities in a mouse model of chronic constriction injury-induced neuropathic pain. We demonstrated that TDAG8 participated alone in mechanical allodynia induced by constriction injury. (1) TDAG8-Na1.8 signaling in small-diameter isolectin B4-positive [IB4(+)] neurons initiates mechanical allodynia; it also modulated substance P release from IB4(-) neurons to facilitate the development of early mechanical allodynia. (2) TDAG8-mediated signaling increased medium-to large-diameter IB4(-) neuron activity to maintain late mechanical allodynia; it also modulated substance P release in soma to reduce satellite glial number and Na1.7 expression, thus attenuating chronic mechanical allodynia.

摘要

外周神经损伤会改变伤害性信号的转导。神经元、神经胶质细胞和免疫细胞之间的协同作用会导致持续性疼痛和炎症。位于伤害感受器和免疫细胞上的T细胞死亡相关基因8（TDAG8）参与炎症性疼痛和关节炎诱导的疼痛。在此，我们利用TDAG8基因敲除小鼠、药理学方法以及钙/钠成像技术，以阐明在慢性压迫损伤诱导的神经性疼痛小鼠模型中，TDAG8介导的信号传导如何调节神经元活动。我们证明TDAG8单独参与了压迫损伤诱导的机械性异常性疼痛。（1）小直径异凝集素B4阳性[IB4(+)]神经元中的TDAG8-Na1.8信号传导引发机械性异常性疼痛；它还调节了IB4(-)神经元中P物质的释放，以促进早期机械性异常性疼痛的发展。（2）TDAG8介导的信号传导增加了中到大直径IB4(-)神经元的活性，以维持晚期机械性异常性疼痛；它还调节了胞体中P物质的释放，以减少卫星神经胶质细胞数量和Na1.7表达，从而减轻慢性机械性异常性疼痛。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/83aa4a3c4b4a/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/1053a48d27fb/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/2dfd81a1f811/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/481e6f5eddfc/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/c4ca7c6b5ed5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/79524859990d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/f5646b03d00b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/8c543c2121a4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/4a5723ce9824/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/eee4221602b7/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/322eef8a33ee/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/83aa4a3c4b4a/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/1053a48d27fb/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/2dfd81a1f811/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/481e6f5eddfc/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/c4ca7c6b5ed5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/79524859990d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/f5646b03d00b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/8c543c2121a4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/4a5723ce9824/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/eee4221602b7/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/322eef8a33ee/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a91/11460492/83aa4a3c4b4a/gr10.jpg

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