Intrathecal administration of Maresin 1 attenuates bone cancer pain by inhibiting the glial cells acti-vation and neuroinflammation in the spinal cord / 临床麻醉学杂志

ABSTRACT

Objective To investigate the effects of intrathecal administration of Maresin 1 on pain behavior and glial cells activation in spinal dorsal horn of mice with bone cancer pain(BCP).Methods Experiment Ⅰ,twenty-eight clean male C57BL/6 mice,aged 4-6 weeks,weighing 18-22 g,were ran-domly divided into two groups:sham 1 group(group S1)and BCP 1 group(group B1),14 mice in each group.BCP model was established in group B1 by injecting PBS 20 μl containing 2 × 105 lewis lung carcino-ma cells into the intramedullary space.Group S,received PBS 20 μl without tumor cells.Six mice in each group were randomly selected to determine the mechanical withdrawal threshold(MWT)and thermal with-drawal latency(TWL)1 day before implantation,3,7,14,21 days after implantation.Four mice were randomly sacrificed on days 7,14 and 21 in group S,and group B1.The expressions of spinal glial fibrillary acidic protein(GFAP)and ionized calcium-binding adapter molecule 1(Iba1)were detected by Western blot.Experiment Ⅱ,thirty-six clean male C57BL/6 mice were randomly divided into three groups:sham 2 group(group S2),BCP 2 group(group B2),and Maresin 1 group(group M),12 mice in each group.BCP models were established in groups B2 and M while group S2 received PBS 20 μl without tumor cells.Maresin 1 50 ng/5 μl were intrathecally injected from days 14 to 16 after tumor cells implantation.Six mice in each group were randomly selected to determine the MWT and TWL on days 14 to 18 after implantation.Mice were sacrificed on day 18 after pain behavior tests.The expressions of spinal GFAP and Iba1 were de-tected by Western blot and immunofluorescence staining.The levels of spinal IL-1 β,IL-6,and TNF-α were detected by ELISA.Results Experiment Ⅰ:compared with group S1,the MWT and TWL were significantly lower on days 7,10,14,and 21 after implantation in group B,(P＜0.05),the expressions of spinal GFAP and Iba1 were upregulated on days 7,14,and 21 after implantation in group B1(P＜0.05).Experiment Ⅱ:compared with group S2,the levels of spinal GFAP,Iba1,IL-1β,IL-6,and TNF-α were increased on day 18 after implantation in group B2(P＜0.05).Compared with group B2,the MWT and TWL were significantly higher on days 15-18 after implantation while levels of spinal GFAP,Iba1,IL-1β,IL-6,and TNF-α on day 18 were decreased in group M(P＜0.05).Conclusion Intrathecal administra-tion of Maresin 1 attenuates BCP maybe by inhibiting the glial cells activation and neuroinflammation in the spinal cord.