Abstract
IntroductionPrevious 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.MethodsIn 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.ConclusionThe 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.
Highlights
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-proteincoupled receptors (GPCRs) such as the l-opioid receptor (MOR)
A battery of pain-related behavioral experiments were applied to Hint1À/À, Hint1+/À, and Hint1+/+ mice to evaluate whether the deficiency of Hint1 gene would modify the peripheral pain sensitivity
The major findings of this study were that the absence of Hint 1 gene enhanced the supraspinal nociceptive sensitivity in mice, including thermal, mechanical, and inflammatory hyperalgesia
Summary
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-proteincoupled receptors (GPCRs) such as the l-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 Hint knockout, heterozygous and wild-type mice. Both the male and female mice were investigated to assess the differences between genders.
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