Lentiviral‑mediated inducible silencing of TLR4 attenuates neuropathic pain in a rat model of chronic constriction injury

Liu,Yantao; Zhang,Yan; Pan,Ruirui; Chen,Mo; Wang,Xiaoqiang; Kong,Erliang; Yu,Weifeng; Sun,Yuming; Wu,Feixiang

doi:10.3892/mmr.2018.9560

Lentiviral‑mediated inducible silencing of TLR4 attenuates neuropathic pain in a rat model of chronic constriction injury

Authors:
- Yantao Liu
- Yan Zhang
- Ruirui Pan
- Mo Chen
- Xiaoqiang Wang
- Erliang Kong
- Weifeng Yu
- Yuming Sun
- Feixiang Wu
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Affiliations: Department of Anesthesiology and Intensive Care, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China, Department of Anesthesiology, Zhejiang Zhoushan Hospital, Zhoushan, Zhejiang 316021, P.R. China
Published online on: October 16, 2018 https://doi.org/10.3892/mmr.2018.9560
Pages: 5545-5551
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

An increasing body of evidence has indicated that spinal microglial Toll‑like receptor 4 (TLR4) may serve a significant role in the development and maintenance of neuropathic pain (NP). In the present study, experiments were conducted to evaluate the contribution of a tetracycline inducible lentiviral‑mediated delivery system for the expression of TLR4 small interfering (si)RNA to NP in rats with chronic constriction injury (CCI). Behavioral tests, including paw withdrawal latency and paw withdrawal threshold, and biochemical analysis of the spinal cord, including western blotting, reverse transcription‑quantitative polymerase chain reaction and ELISA, were conducted following CCI to the sciatic nerve. Intrathecal administration of LvOn‑si‑TLR4 with doxycycline (Dox) attenuated allodynia and hyperalgesia. Biochemical analysis revealed that the mRNA and proteins levels of TLR4 were unregulated following CCI to the sciatic nerve, which was then blocked by intrathecal administration of LvOn‑siTLR4 with Dox. The LvOn‑siTLR4 was also demonstrated to have no effect on TLR4 or the pain response without Dox, which indicated that the expression of siRNA was Dox‑inducible in the lentivirus delivery system. In conclusion, TLR4 may serve a significant role in neuropathy and the results of the present study provide an inducible lentivirus‑mediated siRNA against TLR4 that may serve as a potential novel strategy to be applied in gene therapy for NP in the future.

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