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Papers of the Week

Papers: 27 May 2023 - 2 Jun 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology

Non-Human Pain

2023 Jun 15

Biol Open




The insulin receptor regulates the persistence of mechanical nociceptive sensitization in flies and mice.


Wang Y, Lopez-Bellido R, Huo X, Kavelaars A, Galko MJ


Early phase diabetes is often accompanied by pain sensitization. In Drosophila, the insulin receptor (InR) regulates the persistence of injury-induced thermal nociceptive sensitization. Whether Drosophila InR also regulates the persistence of mechanical nociceptive sensitization remains unclear. Mice with a sensory neuron deletion of the insulin receptor (Insr) show normal nociceptive baselines; however, it is uncertain whether deletion of Insr in nociceptive sensory neurons leads to persistent nociceptive hypersensitivity. In this study, we used fly and mouse nociceptive sensitization models to address these questions. In flies, InR mutants and larvae with sensory neuron-specific expression of RNAi transgenes targeting InR exhibited persistent mechanical hypersensitivity. Mice with a specific deletion of the Insr gene in Nav1.8+ nociceptive sensory neurons showed nociceptive thermal and mechanical baselines similar to controls. In an inflammatory paradigm, however, these mutant mice showed persistent mechanical (but not thermal) hypersensitivity, particularly in female mice. Mice with the Nav1.8+ sensory neuron-specific deletion of Insr did not show metabolic abnormalities typical of a defect in systemic insulin signaling. Our results show that some aspects of the regulation of nociceptive hypersensitivity by the insulin receptor are shared between flies and mice and that this regulation is likely independent of metabolic effects.