Puerarin attenuates remifentanil‑induced postoperative hyperalgesia via targeting PAX6 to regulate the transcription of TRPV1

Yuan,Libang; Liu,Yinghai; Sun,Yangyang; Ren,Ling; Gu,Xiaoping; Chen,Liang; Zhou,Gongrui; Sun,Xiaoqin; Huang,Qingqing; Chen,Xufei; Gong,Gu

doi:10.3892/mmr.2024.13204

Puerarin attenuates remifentanil‑induced postoperative hyperalgesia via targeting PAX6 to regulate the transcription of TRPV1

Authors:
- Libang Yuan
- Yinghai Liu
- Yangyang Sun
- Ling Ren
- Xiaoping Gu
- Liang Chen
- Gongrui Zhou
- Xiaoqin Sun
- Qingqing Huang
- Xufei Chen
- Gu Gong
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Affiliations: Department of Anesthesiology, The General Hospital of Western Theater Command PLA, Chengdu, Sichuan 610083, P.R. China, Department of Anesthesiology, The General Hospital of Western Theater Command PLA, Chengdu, Sichuan 610083, P.R. China
Published online on: March 19, 2024 https://doi.org/10.3892/mmr.2024.13204
Article Number: 81
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Remifentanil‑induced hyperalgesia (RIH) is characterized by the emergence of stimulation‑induced pain, including phenomena such as allodynia and thermal hyperalgesia following remifentanil infusion. As a sequence‑specific DNA binding transcription factor, PAX6 positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system. It was hypothesized that puerarin could relieve RIH via targeting PAX6 to regulate transcription of transient receptor potential cation channel subfamily V Member 1 (TRPV1). A total of 32 rats were randomly divided into five groups, namely control group, RI group, RI + 10 mg/kg puerarin group (RI + puerarin10), RI + 20 mg/kg puerarin group (RI + puerarin20), and RI + 40 mg/kg puerarin group (RI + puerarin40). Mechanical and thermal hyperalgesia were tested at ‑24, 2, 6, 24 and 48 h after remifentanil infusion. Following the sacrifice of rats after the last behavioral test, western blot was used to detect the expression levels of TRPV1 in the tissues; Immunofluorescence staining and western blotting were used to detect the expression of PAX6 in the spinal cord. PharmMapper and JASPAR were used to predict the binding sites of puerarin/PAX6/TRPV1. Chromatin immunoprecipitation‑PCR and dual luciferase reporter assay were used to verify the targeting relationship between PAX6 and TRPV1. Immunofluorescence was used to detect the expression levels of TRPV1 and p‑NR2B. The results revealed that puerarin (10, 20, 40 mg/kg) dose‑dependently reduced thermal and mechanical hyperalgesia from 2 to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of phosphorylated (p‑)NR2B. Nevertheless, the increased amount of p‑NR2B by RIH was dose‑dependently suppressed by puerarin in rats. In conclusion, puerarin was revealed to attenuate postoperative RIH via targeting PAX6 to regulate the transcription of TRPV1.

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