| First Author | Coste O | Year | 2012 |
| Journal | Behav Brain Res | Volume | 234 |
| Issue | 1 | Pages | 121-8 |
| PubMed ID | 22732262 | Mgi Jnum | J:190762 |
| Mgi Id | MGI:5449664 | Doi | 10.1016/j.bbr.2012.06.017 |
| Citation | Coste O, et al. (2012) The p21-activated kinase PAK 5 is involved in formalin-induced nociception through regulation of MAP-kinase signaling and formalin-specific receptors. Behav Brain Res 234(1):121-8 |
| abstractText | p21-activated kinases (PAKs) are involved in signal cascades relevant for nociceptive processing and neuropathic pain. Particularly, the recently described group B PAKs 4, 5 and 6 regulate MAP-kinases and the rearrangement of the actin cytoskeleton, both of which have been linked to pain processing. However, a specific role of these PAKs in nociception has not yet been demonstrated. We found PAK 4, 5 and 6 expression in pain-relevant tissues in peripheral and CNS. Since viable knock-out mice only exist for the PAK isoform 5, we further assessed the impact of this PAK on acute and chronic pain using different behavioral models in mice. PAK 5 knock-out mice showed normal acute nociception and did not differ from wild type mice in their neuropathic pain behavior. However, the nociceptive response in formalin-induced paw inflammation was significantly reduced in knock-out mice associated with inhibition of MAP-kinase activation and a decreased number of formalin-induced c-Fos positive neurons in the spinal cord. Furthermore, in isolated neurons, we found a significantly reduced calcium response after stimulation of TRPA1-channels in PAK 5(-/-)- compared to PAK 5(+/+)-cells. Our results indicate that PAK 5 is involved in formalin-induced inflammatory nociception through regulation of MAPK-induced c-Fos-activation and formalin-specific TRP-channels. |
