Minocycline Relieves Depressive-Like Behaviors in Rats With Bone Cancer Pain by Inhibiting Microglia Activation in Hippocampus

BACKGROUND: Pain and depression are highly prevalent symptoms in cancer patients. They tend to occur simultaneously and affect each other and share biological pathways and neurotransmitters. In this study, we investigated the roles of microglia in the hippocampus in the comorbidity of bone cancer pain and depressive-like behaviors in an animal model of bone cancer pain. METHODS: Bone cancer pain was induced by injection of Walker 256 mammary gland carcinoma cells into the tibia of rats. The effects of intracerebroventricular administration of microglia inhibitor minocycline were examined. RESULTS: Carcinoma intratibia injection caused comorbidity of mechanical allodynia and depressive-like behaviors in rats and activation of microglia in the hippocampus. Both mechanical allodynia and depressive-like behaviors were attenuated by minocycline. Enzyme-linked immunosorbent assay analysis showed that the enhanced expressions of M1 microglia marker (CD 86) and the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the hippocampus of cancer-bearing rats were decreased by minocycline. On the other hand, minocycline also increased the expressions of M2 microglia marker (MRC1) and anti-inflammatory cytokine interleukin-10. CONCLUSIONS: The results suggest that the activation of microglia in the hippocampus plays an important role in the development of pain and depressive-like behaviors in bone cancer condition. Accepted for publication January 3, 2019. The authors declare no conflicts of interest. Funding: Nature Science Foundation of Hunan Province (2018JJ3836 to S.Z.), National Nature Science Foundation of China (81300958 to S.Z.), and Nature Science Foundation of Hunan Province (S2016J504F2145 to Z.J.). Reprints will not be available from the authors. Address correspondence to Zongbin Song, MD, PhD, Department of Anesthesiology, Xiangya Hospital, Central S. University, Hunan, China. Address e-mail to songzb2001@163.com. © 2019 International Anesthesia Research Society

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