title: Activation of notch signaling mediates the induction and maintenance of mechanical allodynia in a rat model of neuropathic pain.
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.
authors.affiliation: Department of Anesthesiology, Tianjin Institute of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Keliang
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, Children's Hospital of Zhengzhou, Zhengzhou, Henan 450053, P.R. China.
authors.forename: Yingping
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Children's Hospital of Zhengzhou, Zhengzhou, Henan 450053, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Anesthesiology, Tianjin Institute of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000235:genetics; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000008:administration & dosage / Q000235:genetics; D009437:Neuralgia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins