Intrathecal injection of LY294002 attenuates bone cancer pain / 中国药理学通报

ABSTRACT

Aim To investigate the effect of intrathecal injection of PI3 K inhibitor LY294002 on pain behav-iour and expression of p-Akt in spinal dorsal horns in bone cancer pain( BCP) rats. Methods Forty female SD rats weighing 180~200 g were randomly divided in-to five groups ( n =8 each ):(Ⅰ) sham group;(Ⅱ) sham+LY294002 group;(Ⅲ) BCP group;(Ⅳ) BCP+DMSO group;( V) BCP+LY294002 group. BCP rat model was induced by inoculating Walker 256 mamma-ry gland carcinoma cells into the medullary cavity of the left tibia. Rats received i. t. injections of either PI3 K inhibitor LY294002 10μL ( 2. 5 g · L-1 ) or 5%DMSO 10 μL at the time of d 7~9 after the operation. Mechanical withdrawal threshold( MWT) test was per-formed before and after i. t. injections on d7(till 8h). The rats were sacrificed after inoculation and the L4~6 segments of the spinal cords were removed for immu-nohistochemistry to determinate the expression changes of spinal p-Akt. Results Compared with I group, the rats inⅢ,Ⅳ,Ⅴgroup showed obvious mechanical hy-peralgesia. The MWT of V group increased apparently from 2nd hour to 4th hour(P<0. 05),and reached the peak in 3rd hour(P<0. 01). Compared with I group, the expression of p-Akt in the spinal cord in Ⅲ,Ⅳgroup increased obviously ( P <0. 01 ) . Compared withⅢ,Ⅳ group,i. t. injections of LY294002 obviously cut down the expression of p-Akt in the spinal cord ( P <0. 05). Conclusion PI3K/Akt singaling pathway may take part in the development of bone cancer pain.