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Activation of PI 3Kγ/Akt pathway mediates bone cancer pain in rats
Author(s) -
Guan Xuehai,
Fu Qiaochu,
Xiong Bingrui,
Song Zhenpeng,
Shu Bin,
Bu Huilian,
Xu Bing,
Manyande Anne,
Cao Fei,
Tian Yuke
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13139
Subject(s) - pi3k/akt/mtor pathway , dorsal root ganglion , bone cancer , sensitization , protein kinase b , spinal cord , microglia , medicine , cancer research , cancer , endocrinology , neuroscience , biology , signal transduction , microbiology and biotechnology , immunology , inflammation
Bone cancer pain ( BCP ) is one of the most common and severe complications in patients suffering from primary bone cancer or metastatic bone 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 PI 3Kγ/Akt in the central sensitization in rats with tumor cell implantation in the tibia, a widely used model of BCP. Our results showed that PI 3Kγ and its downstream target pA kt 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 colocalized with non‐peptidergic, calcitonin gene‐related peptide‐peptidergic, and A‐type neurons in dorsal root ganglion ipsilateral to tumor cell inoculation in rats. Inhibition of spinal PI 3Kγ suppressed BCP‐associated behaviors and the up‐regulation of pA kt in the spinal cord and dorsal root ganglion. This study suggests that PI 3Kγ/Akt signal pathway mediates BCP in rats.Central sensitization is required for the development and maintenance of bone cancer pain (BCP). In this study, we reported that PI3Kγ/Akt mediated the function of ephrinBs/EphBs in the central sensitization under BCP condition, and inhibition of spinal PI3Kγ suppressed BCP‐associated behaviors. Our results suggest that inhibition of PI3Kγ/Akt may be a new target for the treatment of BCP.