Activation of PI3Kγ/Akt pathway mediates bone cancer pain in rats.
J Neurochem. 2015 Apr 28;
Authors: Guan X, Fu Q, Xiong B, Song Z, Shu B, Bu H, Xu B, Manyande A, Cao F, Tian Y
Bone cancer pain (BCP) is one of the most common and severe complications in patients suffering from primary bone cancer or metastatic cancer such as breast, prostate or lung, which profoundly compromises their quality of life. Emerging lines of evidence indicate that central sensitization is required for the development and maintenance of BCP. However, the underlying mechanisms are largely unknown. In this study, we investigated the role of PI3Kγ/Akt in the central sensitization in rats with tumor cell implantation in the rat tibia, a widely used model of bone cancer pain. Our results showed that PI3Kγ and its downstream target pAkt were up-regulated in a time-dependent manner and distributed predominately in the superficial layers of the spinal dorsal horn neurons, astrocytes and a minority of microglia, and were co-localized with non-peptidergic, CGRP-peptidergic, and A-type neurons in dorsal root ganglion (DRG) ipsilateral to tumor cell inoculation in rats. Inhibition of spinal PI3Kγ suppressed bone cancer pain-associated behaviors and the up-regulation of pAkt in the spinal cord and DRG. The present study suggests that PI3Kγ/Akt signal pathway mediates BCP in rats. This article is protected by copyright. All rights reserved.
PMID: 25919859 [PubMed – as supplied by publisher]