Targeting spinal microglia with fexofenadine-loaded nanoparticles prolongs pain relief in a rat model of neuropathic pain

Autor: Quangdon, Tran, Thuy Linh, Pham, Hyo Jung, Shin, Juhee, Shin, Nara, Shin, Hyeok Hee, Kwon, Hyewon, Park, Song I, Kim, Seoung Gyu, Choi, Junhua, Wu, Van T H, Ngo, Jin Bong, Park, Dong Woon, Kim
Rok vydání: 2022
Předmět:
Zdroj: Nanomedicine: Nanotechnology, Biology and Medicine. 44:102576
ISSN: 1549-9634
DOI: 10.1016/j.nano.2022.102576
Popis: Targeting microglial activation is emerging as a clinically promising drug target for neuropathic pain treatment. Fexofenadine, a histamine receptor 1 antagonist, is a clinical drug for the management of allergic reactions as well as pain and inflammation. However, the effect of fexofenadine on microglial activation and pain behaviors remains elucidated. Here, we investigated nanomedicinal approach that targets more preferentially microglia and long-term analgesics. Fexofenadine significantly abolished histamine-induced microglial activation. The fexofenadine-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Fexo NPs) injection reduced the pain sensitivity of spinal nerve ligation rats in a dose-dependent manner. This alleviation was sustained for 4 days, whereas the effective period by direct fexofenadine injection was 3 h. Moreover, Fexo NPs inhibited microglial activation, inflammatory signaling, cytokine release, and a macrophage phenotype shift towards the alternative activated state in the spinal cord. These results show that Fexo NPs exhibit drug repositioning promise as a long-term treatment modality for neuropathic pain.
Databáze: OpenAIRE