Hint1 gene deficiency enhances the supraspinal nociceptive sensitivity in mice.

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.