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超小磁性氧化铁纳米颗粒的表面胺基团在脊髓中产生镇痛作用并降低长时程增强效应。

The Surface Amine Group of Ultrasmall Magnetic Iron Oxide Nanoparticles Produce Analgesia in the Spinal Cord and Decrease Long-Term Potentiation.

作者信息

Lu Guan-Ling, Lin Ya-Chi, Wu Ping-Ching, Liu Yen-Chin

机构信息

Department of Anesthesiology, School of Post-Baccalaureate, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

出版信息

Pharmaceutics. 2022 Feb 6;14(2):366. doi: 10.3390/pharmaceutics14020366.

DOI:10.3390/pharmaceutics14020366
PMID:35214098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8879719/
Abstract

Our previous studies have revealed the ultrasmall superparamagnetic iron oxide in the amine group USPIO-101 has an analgesic effect on inflammatory pain. Here, we further investigated its effect on the spinal cord and brain via electrophysiological and molecular methods. We used a mouse inflammatory pain model, induced by complete Freund's adjuvant (CFA), and measured pain thresholds via von Frey methods. We also investigated the effects of USPIO-101 via an extracellular electrophysiological recording at the spinal dorsal horn synapses and hippocampal Schaffer collateral-CA1 synapses, respectively. The mRNA expression of pro-inflammatory cytokines was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Our results showed intrathecal USPIO-101 produces similar analgesic behavior in mice with chronic inflammatory pain via intrathecal or intraplantar administration. The potentiated low-frequency stimulation-induced spinal cord long-term potentiation (LTP) at the spinal cord superficial dorsal horn synapses could decrease via USPIO-101 in mice with chronic inflammatory pain. However, the mRNA expression of cyclooxygenase-2 was enhanced with lipopolysaccharide (LPS) stimulation in microglial cells, and we also found USPIO-101 at 30 µg/mL could decrease the magnitude of hippocampal LTP. These findings revealed that intrathecal USPIO-101 presented an analgesia effect at the spinal cord level, but had neurotoxicity risk at higher doses.

摘要

我们之前的研究表明，胺基超小超顺磁性氧化铁USPIO-101对炎性疼痛具有镇痛作用。在此，我们通过电生理和分子方法进一步研究了其对脊髓和大脑的影响。我们使用完全弗氏佐剂（CFA）诱导的小鼠炎性疼痛模型，并通过von Frey方法测量疼痛阈值。我们还分别通过在脊髓背角突触和海马体Schaffer侧支-CA1突触处进行细胞外电生理记录来研究USPIO-101的作用。通过定量实时聚合酶链反应（RT-qPCR）检测促炎细胞因子的mRNA表达。我们的结果表明，鞘内注射USPIO-101通过鞘内或足底内给药在患有慢性炎性疼痛的小鼠中产生类似的镇痛行为。在患有慢性炎性疼痛的小鼠中，USPIO-101可降低脊髓浅表背角突触处增强的低频刺激诱导的脊髓长时程增强（LTP）。然而，在小胶质细胞中，脂多糖（LPS）刺激可增强环氧合酶-2的mRNA表达，并且我们还发现30 µg/mL的USPIO-101可降低海马体LTP的幅度。这些发现表明，鞘内注射USPIO-101在脊髓水平呈现镇痛作用，但在高剂量时存在神经毒性风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/525e851e9ec0/pharmaceutics-14-00366-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/b2916c4af9cc/pharmaceutics-14-00366-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/425c6f5ac7a4/pharmaceutics-14-00366-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/280242ccc2d8/pharmaceutics-14-00366-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/a347f71f819b/pharmaceutics-14-00366-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/5c409ea5713c/pharmaceutics-14-00366-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/1b5643840b65/pharmaceutics-14-00366-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/525e851e9ec0/pharmaceutics-14-00366-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/b2916c4af9cc/pharmaceutics-14-00366-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/425c6f5ac7a4/pharmaceutics-14-00366-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/280242ccc2d8/pharmaceutics-14-00366-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/a347f71f819b/pharmaceutics-14-00366-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/5c409ea5713c/pharmaceutics-14-00366-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/1b5643840b65/pharmaceutics-14-00366-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a902/8879719/525e851e9ec0/pharmaceutics-14-00366-g007.jpg

相似文献

[1]
The Surface Amine Group of Ultrasmall Magnetic Iron Oxide Nanoparticles Produce Analgesia in the Spinal Cord and Decrease Long-Term Potentiation.

Pharmaceutics. 2022-2-6

[2]
Magnetic field distribution modulation of intrathecal delivered ketorolac iron-oxide nanoparticle conjugates produce excellent analgesia for chronic inflammatory pain.

J Nanobiotechnology. 2018-5-16

[3]
The induction of long-term potentiation in spinal dorsal horn after peripheral nociceptive stimulation and contribution of spinal TRPV1 in rats.

Neuroscience. 2014-6-6

[4]
The analgesia efficiency of ultrasmall magnetic iron oxide nanoparticles in mice chronic inflammatory pain model.

Nanomedicine. 2017-5-21

[5]
Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain.

J Neuroinflammation. 2017-6-23

[6]
Chemokine CXCL1 enhances inflammatory pain and increases NMDA receptor activity and COX-2 expression in spinal cord neurons via activation of CXCR2.

Exp Neurol. 2014-11

[7]
[The effect of berberine on ameliorating chronic inflammatory pain and depression].

Zhonghua Yi Xue Za Zhi. 2018-4-10

[8]
Role of interleukin-1beta and tumor necrosis factor-alpha-dependent expression of cyclooxygenase-2 mRNA in thermal hyperalgesia induced by chronic inflammation in mice.

Neuroscience. 2008-3-18

[9]
Electroacupuncture attenuates mechanical allodynia by suppressing the spinal JNK1/2 pathway in a rat model of inflammatory pain.

Brain Res Bull. 2014-9

[10]
The Effects of Electroacupuncture on the Apelin/APJ System in the Spinal Cord of Rats With Inflammatory Pain.

Anesth Analg. 2016-12

引用本文的文献

[1]
On the Road to Precision Medicine: Magnetic Systems for Tissue Regeneration, Drug Delivery, Imaging, and Theranostics.

Pharmaceutics. 2023-6-24

本文引用的文献

[1]
Nanotechnology in Chronic Pain Relief.

Front Bioeng Biotechnol. 2020-6-19

[2]
Differences of Microglia in the Brain and the Spinal Cord.

Front Cell Neurosci. 2019-11-14

[3]
Cyclooxygenase-2 modulates ER-mitochondria crosstalk to mediate superparamagnetic iron oxide nanoparticles induced hepatotoxicity: an and study.

Nanotoxicology. 2019-11-8

[4]
Iron oxide nanoparticles for therapeutic applications.

Drug Discov Today. 2020-1

[5]
The neurotoxicity induced by engineered nanomaterials.

Int J Nanomedicine. 2019-6-6

[6]
Preparation of Acute Spinal Cord Slices for Whole-cell Patch-clamp Recording in Substantia Gelatinosa Neurons.

J Vis Exp. 2019-1-18

[7]
Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications.

Adv Drug Deliv Rev. 2019-1-11

[8]
Endoplasmic reticulum stress mediates inflammatory response triggered by ultra-small superparamagnetic iron oxide nanoparticles in hepatocytes.

Nanotoxicology. 2018-11-13

[9]
The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

Nat Commun. 2018-5-25

[10]
Magnetic field distribution modulation of intrathecal delivered ketorolac iron-oxide nanoparticle conjugates produce excellent analgesia for chronic inflammatory pain.

J Nanobiotechnology. 2018-5-16

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