Role of spinal Rac1 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 Rac1 signaling pathway in the maintenance of bone cancer pain (BCP) in rats.Methods:Sixty-four clean-grade adult female Sprague-Dawley rats, aged 8-10 weeks, weighing 180-200 g, were divided into 4 groups using a random number table method: sham operation group (group S, n=8), BCP group ( n=40), BCP plus normal saline group (group BCP+ Veh, n=8), and BCP plus NSC23766 group (group BCP+ NSC, n=8). BCP was induced by injecting Walker 256 mammary gland cancer cell suspension 5 μl (1×10 5 cells/μl) into the bone marrow of the right tibia of rats in BCP, BCP+ Veh and BCP+ NSC groups, while the equal volume of inactivated tumor cells were injected in group S. On 9-11 days after BCP, specific Rac1 inhibitor NSC23766 (5 μg/5 μl) was intrathecally injected once a day in group BCP+ NSC, and the equal volume of normal saline (5 μl) was given once a day in group BCP+ Veh.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before BCP (T 0) and 3, 5, 7, 14 and 21 days after BCP (T 1-5). Eight rats in each group were sacrificed after measurement of MWT at each time point in BCP group or after the last measurement of MWT in S, BCP+ Veh and BCP+ NSC groups, and the lumbar segment (L 4-6) of the spinal cord was removed for determination of the expression of Rac1 signaling pathway-related proteins Rac1, GTP-Rac1, PAK1 and p-PAK1 using Western blot. Results:Compared with group S, MWT was significantly decreased at T 3-5 in BCP, BCP+ Veh and BCP+ NSC groups, and the expression of GTP-Rac1 and p-PAK1 was up-regulated at T 3-5 in group BCP ( P<0.05). Compared with group BCP+ Veh, MWT was significantly increased at T 4, 5, and the expression of GTP-Rac1 and p-PAK1 was down-regulated in group BCP+ NSC ( P<0.05). Conclusion:Spinal Rac1 signaling pathway is involved in the maintenance of BCP in rats.