Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain

作者：Bian Juhua; Zhu Shanshan^*; Ma Wenwen; Li Chunwei; Ashraf, Muhammad Aqeel

来源：Saudi Pharmaceutical Journal, 2016, 24(3): 354-362.

DOI：10.1016/j.jsps.2016.04.017

• ERK1/2
• p90RSK
• Fos protein
• Bone cancer pain
• Intrathecal injection
• Spinal cord

This study is to establish a model of rat tibial osteocarcinoma pain, intrathecally inject specific ERK1/2 inhibitors SCH772984, observe the analgesic effect, and discuss the influence of ERK-P90RSK-Fos signal path in bone cancer pain. Forty female SD rats were randomly divided into 5 groups. Establish a bone cancer pain model after putting the intrathecal tube 5d and determine the rats' mechanical withdrawal threshold (MWT) after tube 5d; 40 SD rats with intrathecal tube back 5d were randomly divided into 5 groups. Sham Group receives no medication, the other four respectively receive 5% DMSO 10 mu l, SCH 0.1, 1.0, 10 mu g (SCH dissolved in 10 mu l 5% DMSO) intrathecally. Determine the rats' mechanical withdrawal threshold (MWT) before and after giving medication 1, 3, 6, 9, 12, 15, 18, 24 h, and 2 min spontaneous paw withdrawal. Western blot and immuno-fluorescence determine the expression condition of spinal cord dorsal horn of p-ERK, p-p90RSK and Fos protein. Intrathecal injection of SCH772984 has analgesic effects on rats with bone cancer pain, and the effects enhance with increasing dose; intrathecal injection of SCH772984 10 mu g could greatly reduce the expression of spinal dorsal horn Fos protein. Injecting walker 256 tumor cells into rats' tibia could cause behavior changes, such as idiopathic pain sensitivity and pain; the intrathecal tube almost has no effect on motor function of rats; ERK1/2 is involved in bone cancer pain, and intrathecal injection of ERK1/2 specific inhibitors SCH772984 10 mu g may effectively relieve bone cancer pain.

• 出版日期2016-5
• 单位徐州医科大学