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.