CX3CR1-Targeted PLGA Nanoparticles Reduce Microglia Activation and Pain Behavior in Rats with Spinal Nerve Ligation

被引：21

作者：

Noh, Chan ^{[1
]}

Shin, Hyo Jung ^{[2
]}

Lee, Seounghun ^{[1
]}

Kim, Song I. ^{[2
]}

Kim, Yoon-Hee ^{[1
]}

Lee, Won Hyung ^{[1
]}

Kim, Dong Woon ^{[2
]}

Lee, Sun Yeul ^{[1
]}

Ko, Young Kwon ^{[1
]}

机构：

[1] Chungnam Natl Univ Hosp, Dept Anesthesiol & Pain Med, 282 Munhwa Ro, Daejeon 35015, South Korea

[2] Chungnam Natl Univ, Brain Res Inst 4, Sch Med, Dept Med Sci,Dept Anat & Cell Biol 3, Daejeon 35015, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

microglia; CX3CR1; Poly(D; L-lactic-co-glycolic acid) (PLGA) nanoparticles; siRNA; neuropathic pain; spinal nerve ligation; NEUROPATHIC PAIN; EXPRESSION; MODEL; CORD; FRACTALKINE; CHEMOKINE; PATHWAY; CX3CR1; MICE;

D O I：

10.3390/ijms21103469

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats. CX3CR1 siRNA-treated rats exhibited significant reductions in the activation of microglia in the spinal dorsal horn and a downregulation of proinflammatory mediators, as well as a significant attenuation of mechanical allodynia. These data indicate that the PLGA-encapsulated CX3CR1 siRNA nanoparticles effectively reduce neuropathic pain in SNL-induced rats by reducing microglial activity and the expression of proinflammatory mediators. Therefore, we believe that PLGA-encapsulated CX3CR1 siRNA nanoparticles represent a valuable new treatment option for neuropathic pain.

引用

页数：12

共 34 条

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