Affiliation:
1. Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment Binzhou Medical University Yantai China
2. The Affiliated Yantai Yuhuangding Hospital of Qingdao University Yantai China
3. University of Tennessee Health Science Center Memphis Tennessee USA
4. Department of Anesthesiology YanTai Affiliated Hospital of BinZhou Medical University Yantai China
Abstract
AbstractBackgroundThere is growing evidence of a strong correlation between pain sensitivity and cognitive function under both physiological and pathological conditions. However, the detailed mechanisms remain largely unknown. In the current study, we sought to explore candidate genes and common molecular mechanisms underlying pain sensitivity and cognitive function with a transcriptome‐wide association study using recombinant inbred mice from the BXD family.MethodsThe pain sensitivity determined by Hargreaves' paw withdrawal test and cognition‐related phenotypes were systematically analyzed in 60 strains of BXD mice and correlated with hippocampus transcriptomes, followed by quantitative trait locus (QTL) mapping and systems genetics analysis.ResultsThe pain sensitivity showed significant variability across the BXD strains and co‐varies with cognitive traits. Pain sensitivity correlated hippocampual genes showed a significant involvement in cognition‐related pathways, including glutamatergic synapse, and PI3K‐Akt signaling pathway. Moreover, QTL mapping identified a genomic region on chromosome 4, potentially regulating the variation of pain sensitivity. Integrative analysis of expression QTL mapping, correlation analysis, and Bayesian network modeling identified Ring finger protein 20 (Rnf20) as the best candidate. Further pathway analysis indicated that Rnf20 may regulate the expression of pain sensitivity and cognitive function through the PI3K‐Akt signaling pathway, particularly through interactions with genes Ppp2r2b, Ppp2r5c, Col9a3, Met, Rps6, Tnc, and Kras.ConclusionsOur study demonstrated that pain sensitivity is associated with genetic background and Rnf20‐mediated PI3K‐Akt signaling may involve in the regulation of pain sensitivity and cognitive functions.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Shandong Province
Cited by
1 articles.
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