1. Academic Validation
  2. Notch signaling activation contributes to paclitaxel-induced neuropathic pain via activation of A1 astrocytes

Notch signaling activation contributes to paclitaxel-induced neuropathic pain via activation of A1 astrocytes

  • Eur J Pharmacol. 2022 Aug 5;928:175130. doi: 10.1016/j.ejphar.2022.175130.
Dan-Yang Li 1 Shao-Jie Gao 1 Jia Sun 1 Long-Qing Zhang 1 Jia-Yi Wu 1 Fan-He Song 1 Dai-Qiang Liu 1 Ya-Qun Zhou 2 Wei Mei 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: yqzhou2019@hust.edu.cn.
  • 3 Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: wmei@hust.edu.cn.
Abstract

Paclitaxel-induced neuropathic pain (PINP) is a progressive and refractory side effect of chemotherapy with few effective treatments at present. It is well-established that astrocytes activation contributes to the development of PINP. Recent reports showed astrocytes can be divided into A1 and A2 phenotypes. However, whether the transformation of astrocytes participates in PINP and the underlying mechanisms remain unknown. As Notch signaling pathway have shown to be involved in neuropathic pain, we aimed to investigate the relationship between Notch signaling pathway and A1 astrocytes in PINP. Herein we found that both A1 astrocytes and Notch signaling were markedly activated in the spinal cord of PINP rats and the downstream molecules of Notch signaling were colocalized with A1 astrocytes. DAPT (an inhibitor of Notch signaling) not only suppressed the mechanical allodynia of PINP rats, but also inhibited the activation of Notch signaling pathway and A1 astrocytes. Furthermore, Jagged1 (a ligand of Notch1 receptors) dose-dependently induced mechanical hyperalgesia in naïve rats and simultaneously led to Notch signaling activation and A1 astrocytes transformation, all of which were inhibited by DAPT. Taken together, these results demonstrate Notch signaling activation contributes to PINP via A1 astrocytes activation, which provides a promising therapeutic target for PINP.

Keywords

A1 astrocytes; DAPT; Hes1; Jagged1; Notch signaling pathway; Paclitaxel-induced neuropathic pain.

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