Activation of PI3Kγ/Akt pathway mediates bone cancer pain in rats.
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 PI3Kγ/Akt in the central sensitization in rats with tumor cell implantation in the tibia, a widely used model of BCP. 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 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 PI3Kγ suppressed BCP-associated behaviors and the up-regulation of pAkt in the spinal cord and dorsal root ganglion. This study suggests that PI3Kγ/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.
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Department of Anesthesiology, Liuzhou Worker's Hospital, the Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China.
Xuehai
X
Guan
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qiaochu
Q
Fu
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bingrui
B
Xiong
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhenpeng
Z
Song
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bin
B
Shu
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huilian
H
Bu
Department of Neurology, Liuzhou Traditional Chinese Medical Hospital, the Third Affiliated Hospital of Guangxi University of Chinese Medicine, Liuzhou, China.
Bing
B
Xu
School of Psychology, Social Work and Human Sciences, University of West London, London, UK.
Anne
A
Manyande
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Fei
F
Cao
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yuke
Y
Tian
D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000150:complications / Q000378:metabolism*; D059333:Central Nervous System Sensitization / Q000502:physiology*; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D007150:Immunohistochemistry; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism
D058544:Class Ib Phosphatidylinositol 3-Kinase; C546765:Pik3cg protein, rat; D051057:Proto-Oncogene Proteins c-akt
Akt; PI3K; bone cancer; pain