Effects of intrathecal methotrexate on activation of microglia in spinal cord in a rat model of tibial cancer pain
10.3760/cma.j.issn.0254-1416.2012.11.006
- VernacularTitle:鞘内注射甲氨蝶呤对胫骨癌痛大鼠脊髓小胶质细胞活化的影响
- Author:
Wen SHEN
;
Dongmei YUE
;
Jiao LIU
;
Liping CHEN
;
Youmiao XU
;
Yan CHEN
;
Xueming HU
- Publication Type:Journal Article
- Keywords:
Methotrexate;
Microglia;
Pain;
Bone neoplasms
- From:
Chinese Journal of Anesthesiology
2012;(11):1311-1313
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effects of intrathecal methotrexate on the activation of microglia in spinal cord in a rat model of tibial cancer pain (TCP).Methods Thirty female Sprague-Dawley rats,aged 5-7 weeks,weighing 150-180 g,were randomly divided into 3 groups (n =10 each):sham operation + artificial cerebrospinal fluid (group SA),TCP + artificial cerebrospinal fluid (group CA),and TCP + methotrexate (group CM).TCP was induced by injecting Walker-256 cancer cells into the medullary cavity of tibia.Artificial cerebrospinal fluid or methotrexate 100μg (15μl) was injected intrathecally over 10 min on 7th day after TCP.Mechanical pain threshold (MPT) was measured before TCP,at 1,3,5 and 7 days after TCP and 2,4,8 and 24 h after administration (T0-8).The rats were sacrificed after measurement of the pain threshold at T8 and the spinal cord was isolated for detection of the activation of microglia (by immunofluorescence) and content of tumor necrosis factor-α (TNF-α) and IL-1β (by ELISA).Results Compared with group SA,MPT was significantly decreased,and the number of activated microglia cells in the spinal cord was increased,and the contents of TNF-α and IL-1β were increased in groups CA and CM (P ＜ 0.05).Compared with group CA,MPT was significantly increased,and the number of activated microglia cells in the spinal cord was decreased,and the contents of TNF-α and IL-1β were decreased in group CM (P ＜ 0.05).Conclusion The mechanism by which intrathecal methotrexate reduces TCP in rats is related to inhibition of the activation of microglia and reduction of the secretion of proinflammatory cytokines TNF-α and IL-1β in the spinal cord.
