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Volume 22
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10.3390/ijms22115657
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Article

IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation

by
Seounghun Lee
1,2,†,
Hyo-Jung Shin
3,4,†,
Chan Noh
2,5,†,
Song-I Kim
3,6,
Young-Kwon Ko
2,5,
Sun-Yeul Lee
2,5,
Chaeseong Lim
2,5,
Boohwi Hong
2,5,
Sin-Young Yang
7,
Dong-Woon Kim
3,4,6,
Won-Hyung Lee
2,5,* and
Yoon-Hee Kim
2,5,*
1
Department of Anesthesiology and Pain Medicine, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong 30099, Korea
2
Department of Anesthesiology and Pain Medicine, College of Medicine, Chungnam National University, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
3
Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon 35015, Korea
4
Brain Research Institute, School of Medicine, Chungnam National University College of Medicine, Daejeon 35015, Korea
5
Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
6
Department of Medical Science, Chungnam National University College of Medicine, Daejeon 35015, Korea
7
Department of Anesthesiology and Pain Medicine, Daejeon Veterans Hospital, 147 Daechoong-ro 82, Daedeok-gu, Daejeon 34314, Korea
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(11), 5657; https://doi.org/10.3390/ijms22115657
Submission received: 13 May 2021 / Revised: 19 May 2021 / Accepted: 21 May 2021 / Published: 26 May 2021
(This article belongs to the Special Issue Nanoparticles and Their Interactions with Target Cells, Host Receptors and Soluble Factors)
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Abstract

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.
Keywords: neuropathic pain; microglia; IKBKB; siRNA; poly (lactic-co-glycolic acid) nanoparticle neuropathic pain; microglia; IKBKB; siRNA; poly (lactic-co-glycolic acid) nanoparticle

Share and Cite

MDPI and ACS Style

Lee, S.; Shin, H.-J.; Noh, C.; Kim, S.-I.; Ko, Y.-K.; Lee, S.-Y.; Lim, C.; Hong, B.; Yang, S.-Y.; Kim, D.-W.; et al. IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation. Int. J. Mol. Sci. 2021, 22, 5657. https://doi.org/10.3390/ijms22115657

AMA Style

Lee S, Shin H-J, Noh C, Kim S-I, Ko Y-K, Lee S-Y, Lim C, Hong B, Yang S-Y, Kim D-W, et al. IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation. International Journal of Molecular Sciences. 2021; 22(11):5657. https://doi.org/10.3390/ijms22115657

Chicago/Turabian Style

Lee, Seounghun, Hyo-Jung Shin, Chan Noh, Song-I Kim, Young-Kwon Ko, Sun-Yeul Lee, Chaeseong Lim, Boohwi Hong, Sin-Young Yang, Dong-Woon Kim, and et al. 2021. "IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation" International Journal of Molecular Sciences 22, no. 11: 5657. https://doi.org/10.3390/ijms22115657

APA Style

Lee, S., Shin, H.-J., Noh, C., Kim, S.-I., Ko, Y.-K., Lee, S.-Y., Lim, C., Hong, B., Yang, S.-Y., Kim, D.-W., Lee, W.-H., & Kim, Y.-H. (2021). IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation. International Journal of Molecular Sciences, 22(11), 5657. https://doi.org/10.3390/ijms22115657

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