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Conditional deletion of Pip5k1c in sensory ganglia and effects on nociception and inflammatory sensitization
Phosphatidylinositol 4-phosphate 5-kinase type 1 gamma (Pip5k1c) generates phosphatidylinositol 4,5-bisphosphate, also known as PI(4,5)P(2) or PIP(2). Many pronociceptive signaling pathways and receptor tyrosine kinases signal via PIP(2) hydrolysis. Previously, we found that pain signaling and pain...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656109/ https://www.ncbi.nlm.nih.gov/pubmed/29020859 http://dx.doi.org/10.1177/1744806917737907 |
Sumario: | Phosphatidylinositol 4-phosphate 5-kinase type 1 gamma (Pip5k1c) generates phosphatidylinositol 4,5-bisphosphate, also known as PI(4,5)P(2) or PIP(2). Many pronociceptive signaling pathways and receptor tyrosine kinases signal via PIP(2) hydrolysis. Previously, we found that pain signaling and pain sensitization were reduced in Pip5k1c(+/−) global heterozygous knockout mice. Here, we sought to evaluate the extent to which dorsal root ganglia selective deletion of Pip5k1c affected nociception in mice. Initially, we crossed sensory neuron-selective Advillin-Cre mice with a conditional Pip5k1c knockout (cKO) allele (Pip5k1c(fl/)(fl)). However, these mice displayed an early onset proprioceptive deficit. To bypass this early onset phenotype, we used two different tamoxifen-inducible Cre lines (Brn3a-Cre-ER(T2) and Advillin-Cre-ER(T2)) to conditionally delete Pip5k1c in adults. Tamoxifen induced high efficiency deletion of PIP5K1C in dorsal root ganglia and slightly reduced PIP5K1C in spinal cord and brain in Brn3a-Cre-ER(T2) × Pip5k1c(fl/)(fl) (Brn3a cKO) mice while PIP5K1C was selectively deleted in dorsal root ganglia with no changes in spinal cord or brain in Advillin-Cre-ER(T2) × Pip5k1c(fl/)(fl) (Advil cKO) mice. Acute thermosensation and mechanosensation were not altered in either line relative to wild-type mice. However, thermal hypersensitivity and mechanical allodynia recovered more rapidly in Brn3a cKO mice, but not Advil cKO mice, following hind paw inflammation. These data collectively suggest that PIP5K1C regulates nociceptive sensitization in more regions of the nervous system than dorsal root ganglia alone. |
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