title: Notch signaling activation is critical to the development of neuropathic pain.
abstract: BACKGROUND
  Nerve injury-induced neuropathic pain is a major health problem worldwide. Notch signaling is a highly conserved pathway in evolution, which has an important role in synaptic plasticity and inflammation in central nervous system. The present study was designed to investigate the potential role of notch signaling in the development of neuropathic pain.
  
  
  METHODS
  The neuropathic pain was induced by spared nerve injury (SNI) in rats. The activation of notch signaling in the lumbar spinal dorsal horn was measured. DAPT, an inhibitor of notch signaling, was intrathecally (i.t.) administered before SNI or after appearance of pain sensitivity. Moreover, Jagged-1 (JAG-1) peptide, a ligand of notch signaling, was i.t. administered to normal rats. The mechanical allodynia was assessed by von Frey test.
  
  
  RESULTS
  Here, we found that DAPT administered 0.5 h before SNI operation could significantly prevent the decrease of mechanical paw withdrawal threshold (PWT) for more than 4 weeks (P < 0.05 vs. SNI group). DAPT administered after appearance of pain sensitivity could also significantly reverse the decrease of mechanical PWT in a dose-dependent manner (P < 0.05). In addition, administration of Jagged-1 (JAG-1) peptide significantly decreased the mechanical PWT of normal rats in a dose-dependent manner (P < 0.05).
  
  
  CONCLUSIONS
  Therefore, notch signaling activation might contribute to the development of neuropathic pain. This study might provide a new therapeutic target for neuropathic pain.
authors.affiliation: Department of Anesthesiology, Tianjin Institute of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, 300052 China.
authors.forename: Keliang
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Orthopedics of Integrated Traditional Chinese and Western Medicine, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, 710054 China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiao
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Tianjin Institute of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, 300052 China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Hou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D009437:Neuralgia / Q000209:etiology* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins
keywords: Mechanical allodynia; Neuropathic pain; Notch signaling pathway
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