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Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions


Reference:

Pezet, S., Marchand, F., D'Mello, R., Grist, J., Clark, A. K., Malcangio, M., Dickenson, A. H., Williams, R. J. and McMahon, S. B., 2008. Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 28 (16), pp. 4261-4270.

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http://dx.doi.org/10.1523/JNEUROSCI.5392-07.2008

Abstract

Here, we show that phosphatidylinositol 3-kinase (PI3K) is a key player in the establishment of central sensitization, the spinal cord phenomenon associated with persistent afferent inputs and contributing to chronic pain states. We demonstrated electrophysiologically that PI3K is required for the full expression of spinal neuronal wind-up. In an inflammatory pain model, intrathecal administration of LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], a potent PI3K inhibitor, dose-dependently inhibited pain-related behavior. This effect was correlated with a reduction of the phosphorylation of ERK (extracellular signal-regulated kinase) and CaMKII (calcium/calmodulin-dependent protein kinase II). In addition, we observed a significant decrease in the phosphorylation of the NMDA receptor subunit NR2B, decreased translocation to the plasma membrane of the GluR1 (glutamate receptor 1) AMPA receptor subunit in the spinal cord, and a reduction of evoked neuronal activity as measured using c-Fos immunohistochemistry. Our study suggests that PI3K is a major factor in the expression of central sensitization after noxious inflammatory stimuli.

Details

Item Type Articles
CreatorsPezet, S., Marchand, F., D'Mello, R., Grist, J., Clark, A. K., Malcangio, M., Dickenson, A. H., Williams, R. J. and McMahon, S. B.
DOI10.1523/JNEUROSCI.5392-07.2008
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code18421

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