Effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in rats with bone cancer pain / 中国药房

ABSTRACT

OBJECTIVE To study the effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in rats with bone cancer pain. METHODS After treatment via intrathecal tube ，the rats were randomly divided into sham operation group ，model group ，resveratrol low-dose ，medium-dose and high-dose groups （0.25，1，2 mg/kg），with 8 rats in each group. Except for sham operation group ，other groups were given Walker 256 breast cancer cell suspension on the right hind limb tibia to induce bone cancer pain model. After 12 days of modeling ，intrathecal administration was performed in resveratrol groups. The model group and sham operation group received the same volume of dimethyl sulfoxide ，10 μL，once a day ，for 5 days. The paw withdrawal mechanical threshold （PWMT）and paw withdrawal thermal latency （PWTL）were measured at 3 d，5 d after administration. The serum levels of tumor necrosis factor α（TNF-α），interleukin 6（IL-6），IL-1β and chemokine ligand 2 （CCL2）were determined after last medication ，and the protein expressions of RANK ，RANK-L and OPG in tibia were also determined. RESULTS Compared with sham operation group ，PWMT and PWTL were significantly decreased in the model group 12 days after operation （P＜0.05）. Compared with model group ，PWMT and PWTL were significantly increased in resveratrol medium-dose and high-dose groups at 3 d and 5 d after administration （P＜0.05）. Compared with model group ，the levels of TNF-α，IL-6，IL-1β and CCL2 in serum were significantly decreased in resveratrol middle-dose and high-dose groups at 5 d after administration（P＜0.05）；the expression of IL- 6 in serum was significantly decreased in resveratrol low-dose group （P＜0.05）； the protein expressions of RANK-L and RANK in tibia were significantly decreased ，while the protein expression of OPG was increased significantly in resveratrol middle-dose group （P＜0.05）. CONCLUSIONS Resveratrol by intrathecal injection can relieve the inflammation caused by bone cancer pain of rats ， the mechanism of which may be associated with inhibiting the activity of OPG/RANK/RANK-L signal pathway.