CX3CR1-Targeted PLGA Nanoparticles Reduce Microglia Activation and Pain Behavior in Rats with Spinal Nerve Ligation.
Animals
Behavior, Animal
/ drug effects
CX3C Chemokine Receptor 1
/ antagonists & inhibitors
Humans
Ligation
Lipopolysaccharides
/ pharmacology
Macrophage Activation
/ drug effects
Microglia
/ drug effects
Nanoparticles
/ chemistry
Neuralgia
/ drug therapy
Pain Management
Pain Measurement
/ methods
Polylactic Acid-Polyglycolic Acid Copolymer
/ chemistry
RNA, Small Interfering
/ genetics
Rats
Spinal Cord
/ drug effects
Spinal Cord Dorsal Horn
/ drug effects
Spinal Nerves
/ drug effects
CX3CR1
Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles
microglia
neuropathic pain
siRNA
spinal nerve ligation
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
14 May 2020
14 May 2020
Historique:
received:
23
04
2020
revised:
08
05
2020
accepted:
12
05
2020
entrez:
20
5
2020
pubmed:
20
5
2020
medline:
12
2
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32423102
pii: ijms21103469
doi: 10.3390/ijms21103469
pmc: PMC7279022
pii:
doi:
Substances chimiques
CX3C Chemokine Receptor 1
0
CX3CR1 protein, rat
0
Lipopolysaccharides
0
RNA, Small Interfering
0
Polylactic Acid-Polyglycolic Acid Copolymer
1SIA8062RS
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research Foundation of Korea
ID : NRF- 2019R1A2C2004884, NRF- 2020R1A2C1007575 and NRF-2020R1C1C1005423
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