Role of spinal IKK2/NF-κB signaling pathway in maintenance of bone cancer pain in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of spinal IKK2/NF-κB pathway in the maintenance of bone cancer pain (BCP) in rats.Methods Twenty-eight unmated adult female Sprague-Dawley rats,weighing 160-200 g,were randomly divided into 4 groups (n =7 each) using a random number tablesham operation group (group S),BCP group (group BP),BCP + normal saline group (group BN),and BCP + BMS345541 group (group BB).BCP was induced by injecting Walker 256 mammary gland cancer cell suspension 5 μl (4 × 105 cells/ml) into the bone marrow of the right tibia of rats anesthetized with chloral hydrate in BP,BN and BB groups,while the equal volume of normal saline was injected in group S.On 10-12 days after operation,selective IKK2 inhibitor BMS345541 (50 μg/10 μl) was intrathecally injected once a day in group BB,and the equal volume of normal saline (10μl) was given once a day in group BN.The mechanical paw withdrawal threshold (MWT) was measured before intra-tibia injection (T0),on 7 days after intra-tibia injection (T1),at 1 h before drug administration and 1,2,4,12 and 24 h after drug administration on day 10 after operation,and at 4 h after drug administration on day 12 after operation (T2-8).The rats were sacrificed after MWT was measured at Ts and L4-6 segments of the spinal cord were removed for determination of phosphorylated NF-κB (p-NF-κB) expression (using Western blot analysis).Results Compared with group S,MWT was significantly decreased at T1-2,and the expression of p-NF-κB was up-regulated in BP,BN,and BB groups.Compared with group BP,MWT was significantly increased at T4-6,and the expression of p-NF-κB in the spinal cord was down-regulated in group BB.Conclusion Spinal IKK2/NF-κB signaling pathway is involved in the maintenance of bone cancer pain in rats.