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TGF-β 超家族成员在腰椎背根神经节中的转录谱及激活素 A 和 C 对大鼠炎性疼痛的影响。

Transcriptional profiles of TGF-β superfamily members in the lumbar DRGs and the effects of activins A and C on inflammatory pain in rats.

机构信息

School of Pharmacy, Nantong University, Jiangsu Province, 226001, Nantong, China.

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.

出版信息

J Physiol Biochem. 2023 May;79(2):313-325. doi: 10.1007/s13105-022-00943-z. Epub 2023 Jan 25.


DOI:10.1007/s13105-022-00943-z
PMID:36696051
Abstract

Signaling by the transforming growth factor (TGF)-β superfamily is necessary for proper neural development and is involved in pain processing under both physiological and pathological conditions. Sensory neurons that reside in the dorsal root ganglia (DRGs) initially begin to perceive noxious signaling from their innervating peripheral target tissues and further convey pain signaling to the central nervous system. However, the transcriptional profile of the TGF-β superfamily members in DRGs during chronic inflammatory pain remains elusive. We developed a custom microarray to screen for transcriptional changes in members of the TGF-β superfamily in lumbar DRGs of rats with chronic inflammatory pain and found that the transcription of the TGF-β superfamily members tends to be downregulated. Among them, signaling of the activin/inhibin and bone morphogenetic protein/growth and differentiation factor (BMP/GDF) families dramatically decreased. In addition, peripherally pre-local administration of activins A and C worsened formalin-induced acute inflammatory pain, whereas activin C, but not activin A, improved formalin-induced persistent inflammatory pain by inhibiting the activation of astrocytes. This is the first report of the TGF-β superfamily transcriptional profiles in lumbar DRGs under chronic inflammatory pain conditions, in which transcriptional changes in cytokines or pathway components were found to contribute to, or be involved in, inflammatory pain processing. Our data will provide more targets for pain research.

摘要

转化生长因子 (TGF)-β 超家族的信号转导对于正常的神经发育是必要的,并且在生理和病理条件下都参与疼痛处理。位于背根神经节 (DRG) 的感觉神经元最初开始感知其支配的周围靶组织的有害信号,并进一步将疼痛信号传递到中枢神经系统。然而,在慢性炎症性疼痛期间,DRG 中 TGF-β 超家族成员的转录谱仍然难以捉摸。我们开发了一种定制的微阵列来筛选慢性炎症性疼痛大鼠腰椎 DRG 中 TGF-β 超家族成员的转录变化,发现 TGF-β 超家族成员的转录往往下调。其中,激活素/抑制素和骨形态发生蛋白/生长和分化因子 (BMP/GDF) 家族的信号显著降低。此外,激活素 A 和 C 的外周预先局部给药加重了福尔马林诱导的急性炎症性疼痛,而激活素 C 而非激活素 A 通过抑制星形胶质细胞的激活改善了福尔马林诱导的持续性炎症性疼痛。这是慢性炎症性疼痛条件下腰椎 DRG 中 TGF-β 超家族转录谱的首次报道,其中细胞因子或途径成分的转录变化被发现有助于或参与炎症性疼痛处理。我们的数据将为疼痛研究提供更多的目标。

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Transcriptional profiles of TGF-β superfamily members in the lumbar DRGs and the effects of activins A and C on inflammatory pain in rats.

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[2]
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[7]
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引用本文的文献

[1]
Optogenetic Activation of Peripheral Somatosensory Neurons in Transgenic Mice as a Neuropathic Pain Model for Assessing the Therapeutic Efficacy of Analgesics.

ACS Pharmacol Transl Sci. 2023-12-13

[2]
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Mol Med Rep. 2024-1

本文引用的文献

[1]
The orphan ligand, activin C, signals through activin receptor-like kinase 7.

Elife. 2022-6-23

[2]
Growth Differentiation Factor-15 Produces Analgesia by Inhibiting Tetrodotoxin-Resistant Nav1.8 Sodium Channel Activity in Rat Primary Sensory Neurons.

Neurosci Bull. 2021-9

[3]
Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel.

Br J Pharmacol. 2020-12

[4]
Activin and inhibin signaling: From regulation of physiology to involvement in the pathology of the female reproductive system.

Cytokine. 2020-9

[5]
Intra-articular injection of 2-pyridylethylamine produces spinal NPY-mediated antinociception in the formalin-induced rat knee-joint pain model.

Brain Res. 2020-5-15

[6]
Failure of Placebo Analgesia Model in Rats with Inflammatory Pain.

Neurosci Bull. 2019-8-21

[7]
Inhibition of Muscular Nociceptive Afferents via the Activation of Cutaneous Nociceptors in a Rat Model of Inflammatory Muscle Pain.

Neurosci Bull. 2019-6-22

[8]
Upregulation of bone morphogenetic protein 2 ( Bmp2) in dorsal root ganglion in a rat model of bone cancer pain.

Mol Pain. 2019

[9]
Growth and differentiation factor 15 is a biomarker for low back pain-associated disability.

Cytokine. 2019-2-15

[10]
TGFβ and BMPRII signalling pathways in the pathogenesis of pulmonary arterial hypertension.

Drug Discov Today. 2018-12-7

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