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Local and Global Methods of Assessing Thermal Nociception in Drosophila Larvae
Published on: May 18, 2012
The insulin receptor regulates the persistence of mechanical nociceptive sensitization in flies and mice
Yan Wang1, Roger Lopez-Bellido1, Xiaojiao Huo2
1Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
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.
Insights
The insulin receptor (InR) in Drosophila and mice regulates persistent mechanical pain hypersensitivity. This effect in mice was observed in sensory neurons and was independent of metabolic changes, particularly in females.
Area of Science:
- Neuroscience
- Genetics
- Pain Research
Background:
- Early diabetes can cause pain sensitization.
- The insulin receptor (InR) in Drosophila influences thermal pain sensitization after injury.
- The role of InR in mechanical pain sensitization is not well understood.
Purpose of the Study:
- To investigate the role of the insulin receptor in mechanical pain sensitization in Drosophila and mice.
- To determine if insulin receptor deletion in sensory neurons affects nociceptive baselines and hypersensitivity.
- To explore the independence of this regulation from metabolic effects.
Main Methods:
- Used Drosophila models with InR mutations and RNAi targeting InR in sensory neurons.
- Generated mice with sensory neuron-specific deletion of the insulin receptor (Insr) gene.
- Assessed nociceptive thermal and mechanical baselines and hypersensitivity in response to inflammatory stimuli.
Main Results:
- Drosophila InR mutants and larvae with sensory neuron-specific InR knockdown showed persistent mechanical hypersensitivity.
- Mice with sensory neuron-specific Insr deletion had normal nociceptive baselines but exhibited persistent mechanical hypersensitivity after inflammation, especially females.
- These mutant mice did not display metabolic abnormalities associated with systemic insulin signaling defects.
Conclusions:
- The insulin receptor plays a conserved role in regulating persistent mechanical pain hypersensitivity across species.
- Insulin receptor regulation of nociception in sensory neurons is likely independent of systemic metabolic effects.
- Sex-specific differences in mechanical hypersensitivity regulation by the insulin receptor warrant further investigation.
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