Arbuckle MI, Komiyama NH, Delaney A, Coba M, Garry EM, Rosie R, Allchorne AJ, Forsyth LH, Bence M, Carlisle HJ, O'Dell TJ, Mitchell R, Fleetwood-Walker SM, Grant SG (2010) “The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment.” EMBO Rep 11(6):473-8
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-C2alpha 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.
|Online links:||Available online from Nature Publishing Group|
|Publication type:||Journal Article|
|Publication status:||In print, Electronically published|
|Publication date:||2010 Jun|
|Electronic publication date:||2010 May 14|
|Record status:||PubMed - indexed for MEDLINE|