Analgesia effects of quinpirole via intrathecal injection and its influence on spinal microglia activation in rats with bone cancer pain

MENGGEN Qiqige; ZHANG Chunyu; LUO Jianjun; ZHANG Yi

Abstract：Objective To explore the analgesia effects of quinpirole ( QNP ) via intrathecal injection and its influence on spi-nal microglia activation in rats with bone cancer pain. Methods Sixty adult male SD rats were used to establish bone cancer pain mod-el by intra-tibia inoculation of Walker256 mammary gland carcinoma cells. The rats with bone cancer pain were randomly divided into 3 groups:high-dose QNP ( QNP-H) group, low-dose QNP ( QNP-L) group and normal saline ( NS) group, with 20 rats in each group. QNP-H group and QNP-L group received intrathecal injection of 10μl QNP at the dose of 10 and 5μg/kg, respectively. Another 20 male SD rats were chosen as control ( C) group and received the same volume of saline as NS group. Pain behaviors were assessed be-fore treatment and 1, 3, 5 and 7d during treatment to analyze the paw mechanical withdrawal threshold ( MWT) and paw withdrawal thermal latency ( WTL) . The immunohistochemistry was employed to evaluate the spinal microglia number ionized calcium binding ada-ptor molecule 1 and activation by the integral optical density ( IOD) of C3 complement receptor ( OX-42) and cannabinoid receptor 2 ( CB2) . The spinal levels of TNF-αand IL-1βwere measured by enzyme linked immunosorbent assay. Moreover, the protein levels of spinal Toll like receptor-4 ( TLR-4) and its receptor-2 ( TLR-2) were detected by Western blotting. Results Compared with C group, there were lower MWT and WTL, but higher spinal microglia number, IOD of OX-42 and CB2, TNF-α, IL-1β, TLR-2 and TLR-4 in NS, QNP-L and QNP-H groups with significant difference ( P<0. 05) . Intrathecal injection of QNP improved the above abnormalities of rats with bone cancer pain compared with NS group ( P<0. 05) . The effect of QNP-H group was stronger than that of QNP-L group ( P<0. 05) . Conclusion Intrathecal injection of QNP exhibits a good analgesic effect on bone cancer pain and inhibits spinal microglia ac-tivation and inflammatory reaction.