Effect of minocycline on spinal CX3 C chemokine receptor 1 mRNA expression in morphine-tolerant rats with bone cancer pain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of minocycline on spinal CX3 C chemokine receptor 1(CX3 CR1)mRNA expression in morphine-tolerant rats with bone cancer pain.Methods Sixty female SD rats weighing 180-200 g in which intrathecal(IT)catheter was successfully placed at L3,4 interspace without complications were randomly divided into 4 groupscontrol group(group C,n=10);minocycline group(group M,n=10);bone cancer pain + morphine tolerance group(group BM,n=20)and bone cancer pain+morphine tolerance+ minocycline group(group BM+M,n=20).Bone cancer pain was induced by injection of breast cancer cells(Walker256)10μl(400/μl)into upper segment of bone marrow of right tibia.Morphine tolerance was induced by IT injection of morphine 20 μg/kg twice a day for 7 consecutive days starting from the 10th day after intratibia injection in BM and BM + M groups. Minocycline 0.25 mg/kg was injected IT once a day for 3 consecutive days in group M and after the model of bone cancer pain and morphine tolerance was established in group BM + M. Mechanical withdrawal threshold (MWT) and mechanical withdrawal duration (MWD) were determined before (T0, baseline) and at3, 6 and 9 days after operation (T1-3) and at 4, 7, 10 and 12 days after IT morphine injection was started (T4-7).The animals were sacrificed at T6 and T7 respectively in BM and BM + M groups and at T7 in C and M groups.The lumbar segment of the spinal cord (L4-6) was removed for determination of CX3 CR1 mRNA (by RT-PCR) and OX-42 expression (by immuno-histochemistry) .Results There was no significant difference in MWT and MWD at all time points between group C and group M. MWT was significantly decreased while MWD prolonged in morphine tolerant rats with cancer pain in group BM as compared with C and M groups. The hyperalgesia was significantly attenuated by IT minocycline in group BM + M. Spinal CX3 CR1 mRNA and OX-42 expression was significantly increased in group BM than in C and M groups. IT minocycline attenuated the increase in spinal CX3 CR, mRNA and OX-42 expression induced by bone cancer. Conclusion IT minocycline can inhibit spinal CX3CR1 mRNA expression, thereby antagonizing morphine tolerance in morphine-tolerant rats with bone cancer pain.