CX3CR1-Targeted PLGA Nanoparticles Reduce Microglia Activation and Pain Behavior in Rats with Spinal Nerve Ligation.
Chan NohHyo-Jung ShinSeounghun LeeSong I KimYoon-Hee KimWon Hyung LeeDong Woon KimSun Yeul LeeYoung Kwon KoPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- neuropathic pain
- spinal cord
- cancer therapy
- spinal cord injury
- drug delivery
- drug release
- inflammatory response
- lps induced
- walled carbon nanotubes
- bone regeneration
- endothelial cells
- induced apoptosis
- electronic health record
- toll like receptor
- binding protein
- atomic force microscopy
- deep learning
- endoplasmic reticulum stress
- newly diagnosed
- data analysis
- structural basis