Activation of notch signaling mediates the induction and maintenance of mechanical allodynia in a rat model of neuropathic pain

Xie,Keliang; Jia,Yingping; Hu,Ying; Sun,Yanyan; Hou,Lichao; Wang,Guolin

doi:10.3892/mmr.2015.3379

Activation of notch signaling mediates the induction and maintenance of mechanical allodynia in a rat model of neuropathic pain

Authors:
- Keliang Xie
- Yingping Jia
- Ying Hu
- Yanyan Sun
- Lichao Hou
- Guolin Wang
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Affiliations: Department of Anesthesiology, Tianjin Institute of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China, Department of Anesthesiology, Children's Hospital of Zhengzhou, Zhengzhou, Henan 450053, P.R. China, Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: February 20, 2015 https://doi.org/10.3892/mmr.2015.3379
Pages: 639-644

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Abstract

Neuropathic pain is a major health problem caused by dysfunction or damage of the nerve fibers in the peripheral or central nervous system. Notch signaling is a highly conserved evolutionary pathway, which regulates the fate of cells in the developing nervous system and is important in synaptic plasticity and inflammation in the adult central nervous system. The aim of the present study was to investigate the potential roles of the notch signaling pathway in the induction and maintenance of mechanical allodynia in neuropathic pain. Neuropathic pain was induced through spared nerve injury (SNI) in rats. DAPT, a γ‑secretase inhibitor of the notch signaling pathway, was intrathecally administered at different concentrations (5, 15, 50 and 150 µM), and time-points. In addition, Jagged‑1 (JAG‑1) peptide, a ligand of the notch signaling pathway, was administered intrathecally to normal rats. The mechanical allodynia was assessed using a von Frey test. The results demonstrated that administering DAPT prior to the appearance of pain sensitivity significantly prevented the decrease of mechanical paw withdrawal threshold (PWT) for >4 weeks (P<0.05 vs. SNI group). Administering DAPT following the appearance of pain sensitivity significantly reversed the decrease of mechanical PWT (P<0.05 vs. SNI group). Furthermore, early and late administration of DAPT resulted in dose‑dependent antinociceptive effects. In addition, administration of JAG‑1 induced a dose‑dependent increase in the mechanical PWT of the normal rats. In conclusion, the results of the present study demonstrated that activation of notch signaling contributed to the induction and maintenance of mechanical allodynia in neuropathic pain, suggesting a potential novel therapeutic target for the treatment of neuropathic pain.

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