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Minocycline‐induced reduction of brain‐derived neurotrophic factor expression in relation to cancer‐induced bone pain in rats
Author(s) -
Wang Lina,
Yang Jianping,
Zhan Ying,
Ji Fuhai,
Wang Xiuyun,
Zuo Jianling,
Xu Qinian
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22788
Subject(s) - minocycline , brain derived neurotrophic factor , medicine , microglia , neurotrophic factors , spinal cord , pharmacology , bone pain , anesthesia , inflammation , chemistry , receptor , biochemistry , psychiatry , antibiotics
Previous studies have suggested that the release of brain‐derived neurotrophic factor (BDNF) from microglia in spinal cord is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about its role in cancer‐induced bone pain (CIBP), which is in some ways unique. This study demonstrates a critical role of minocycline (a potent inhibitor of microglial activation)‐modulated BDNF in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP. We assessed mechanical threshold and spontaneous pain of CIBP rats. Moreover, minocycline was administered intrathecally from day 4 to day 6 (early stage) or from day 10 to day 12 (later stage), after carcinoma cell inoculation. Real‐time PCR, Western blots, and double immunofluorescence were used to detect the expression of OX‐42 (marker of activated microglia), phosphorylated p38‐MAPK (p‐p38), and BDNF. We found that intrathecal minocycline could prevent CIBP at an early stage of tumor growth (from day 4 to day 6). However, at the late stage (from day 10 to day 12), intrathecal minocycline had no effect. Moreover, the expression of OX‐42 and BDNF under CIBP, peaking on day 6, were all reduced after minocycline injection from day 4 to day 6. The ability of minocycline‐induced reduction of BDNF in the induction of behavioral hypersensitivity could provide an opportunity for alleviating CIBP. © 2011 Wiley Periodicals, Inc.