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The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol‐3‐kinase recruitment |
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| Authors: | Marcelo Coba Emer M Garry Roberta Rosie Andrew J Allchorne Lynsey H Forsyth Matthew Bence Holly J Carlisle Thomas J O'Dell Rory Mitchell Seth G N Grant |
| Institution: | 1. The Wellcome Trust Sanger Institute, Genome Campus, Genes to Cognition Programme, Hinxton, Cambridgeshire, CB10 1SA UK;2. Centre for Neuroregeneration, The University of Edinburgh, Institute of Immunology and Infection, Ashworth Buildings, Kings Buildings, Edinburgh, EH9 3JT UK;3. Department of Physiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, California, 90024 USA |
| Abstract: | Sensitization to inflammatory pain is a pathological form of neuronal plasticity that is poorly understood and treated. Here we examine the role of the SH3 domain of postsynaptic density 95 (PSD95) by using mice that carry a single amino‐acid substitution in the polyproline‐binding site. Testing multiple forms of plasticity we found sensitization to inflammation was specifically attenuated. The inflammatory response required recruitment of phosphatidylinositol‐3‐kinase‐C2α to the SH3‐binding site of PSD95. In wild‐type mice, wortmannin or peptide competition attenuated the sensitization. These results show that different types of behavioural plasticity are mediated by specific domains of PSD95 and suggest novel therapeutic avenues for reducing inflammatory pain. |
| Keywords: | nociception inflammation PSD95 SH3 domain |