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Hint1 gene deficiency enhances the supraspinal nociceptive sensitivity in mice
1College 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.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
