Role of spinal PI3K/Akt signaling pathway in maintenance of bone cancer pain in rats: the relationship with microglial activation

Objective To evaluate the role of spinal phosphatidyl-inositol 3-kinase/Akt (PI3k/Akt) signaling pathway in the maintenance of bone cancer pain (BCP) in rats and its relationship with microglial activation.Methods Forty healthy female Sprague-Dawley rats,weighing 180-200 g,were randomly divided into 5 groups (n =8 each):sham operation group (group S) ; PI3K inhibitor LY294002 group (group L) ; group BCP; BCP + dimethyl sulfoxide (DMSO) group (group BCP + D) ; BCP + LY294002 group (group BCP + L).BCP was induced by inoculating Walker 256 mammary gland carcinoma cells into the medullary cavity of the left tibia.At 7-9 days after inoculation,LY294002 2.5 μg/10 μl was injected intrathecally in L and BCP + L groups,normal saline 10 μl was injected intrathecally in S and BCP groups,and 5％ DMSO 10 μl was injected intrathecally in BCP+ D group once a day.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before inoculation and 1,3,5,7,8 and 9 days after inoculation.The rats were sacrificed after MWT was measured on day 9 after inoculation and the L4-6 segments of the spinal cord were removed to determinate the activation of spinal microglia using immunofluorescence.Results Compared with group S,MWT was significantly decreased,and the activation of spinal microglia was increased in BCP,BCP + D and BCP+ L groups.Compared with BCP and BCP + D groups,MWT was significantly increased,and the activation of spinal microglia was decreased in BCP + D group.Conclusion Spinal PI3K/Akt signaling pathway is involved in the maintenance of BCP possibly through activating microglia in spinal dorsal horns of rats. Key words: Bone neoplasms ;  Pain;  1-Phosphatidylinositol 3-kinase;  Protein-serine-threonine kinases ;  Nicroglia;  Spinal cord