title: Hint1 gene deficiency enhances the supraspinal nociceptive sensitivity in mice.
abstract: Previous studies have indicated a possible role of histidine triad nucleotide-binding protein 1 (HINT1) on sustaining the regulatory crosstalk of N-methyl-D-aspartate acid glutamate receptors (NMDARs) and G-protein-coupled receptors (GPCRs) such as the μ-opioid receptor (MOR). Both receptors are present in the midbrain periaqueductal gray neurons, an area that plays a central role in the supraspinal antinociceptive process.
  
  
  
  In the present study, a battery of pain-related behavioral experiments was applied to Hint1 knockout, heterozygous and wild-type mice. Both the male and female mice were investigated to assess the differences between genders.
  
  
  
  Hint1-/- mice presented significant shorter latency at 50°C in both male and female in hot plate test while no significant difference was found in tail filck test. In Von Frey hairs test Hint1-/- mice were more sensitive than Hint1+/+ mice, presenting a lower withdrawal threshold and enhanced relative frequency of paw withdrawal. The average flinches and licking time of Hint1-/- mice were more than that of Hint1+/+ mice in formalin test.
  
  
  
  The absence of Hint1 gene-enhanced supraspinal nociceptive sensitivity in mice, including thermal, mechanical and inflammatory hyperalgesia. Meanwhile, there was no certain evidence indicating the haploinsufficiency and gender differences of Hint1 gene in pain-related behaviors.
authors.affiliation: College of Medicine & Forensics Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China; Affiliated Stomatology Hospital of Xi'an Jiaotong University Health Science Center Xi'an 710004 Shaanxi China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Affiliated Stomatology Hospital of Xi'an Jiaotong University Health Science Center Xi'an 710004 Shaanxi China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: College of Medicine & Forensics Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: College of Medicine & Forensics Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chu
authors.affiliation: College of Medicine & Forensics Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lei
authors.affiliation: College of Medicine & Forensics Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China; Key Laboratory of the Health Ministry for Forensic Medicine Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China; Key Laboratory of Forensic Medicine of Shaanxi Province Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China.
authors.forename: Xiao-di
authors.initials: XD
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutical Sciences University of Maryland School of Pharmacy Baltimore Maryland 21201.
authors.forename: Jia-Bei
authors.initials: JB
authors.lastname: Wang
authors.affiliation: College of Medicine & Forensics Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China; Key Laboratory of the Health Ministry for Forensic Medicine Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China; Key Laboratory of Forensic Medicine of Shaanxi Province Xi'an Jiaotong University Health Science Center Xi'an 710061 Shaanxi China.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Dang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005260:Female; D057895:Haploinsufficiency; D008297:Male; D008636:Mesencephalon; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D059225:Nociception / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology*; D012737:Sex Factors
chemical_list: C489275:Hint1 protein, mouse; D009419:Nerve Tissue Proteins
keywords: Gender differences; Hint1; haploinsufficiency; mice; supraspinal nociceptive sensitivity