Dexmedetomidine prevents morphine tolerance and its the influence on gliocyte and ERK in spinal cord

Aim To investigate the influence of dexmedetomidine on analgesic effect of morphine in normal rats and the possible underlying molecular mechanism. Methods Forty-eight male SpragueDawley rats were randomly divided into six groups( n =8) : saline control group( groupⅠ),morphine tolerance group( groupⅡ),50 μg·kg- 1dexmedetomidine control group( group Ⅲ),12. 5 μg · kg- 1dexmedetomidine treatment group( group Ⅳ),25 μg·kg- 1dexmedetomidine treatment group( group Ⅴ),and 50 μg·kg- 1dexmedetomidine treatment group( group Ⅵ). On the first day,the basic paw withdrawal thermal latency( PWTL) was evaluated,then the percentage of maximal possible effect( % MPE) was calculated 30 min after morphine( 10 mg·kg- 1) was administered subcutaneously. On day 2,rats were treated with subcutaneous injections of either saline( group Ⅰ) or 10 mg·kg- 1morphine( group Ⅱ) twice daily at 8: 00 and17: 00 for 5 days; groupⅢ were injected 50 μg·kg- 1dexmedetomidine once daily every morning and equal saline every afternoon. Rats were injected 10 mg ·kg- 1morphine and respective dexmedetomidine( groupⅣ,Ⅴ,Ⅵ) 30 min before the injections of morphine twice daily for 5 consecutive days. On day 7,Lumbar5 spinal cord was obtained immediately after the behavioral tests to determine the expression of ERK and pERK by Western bolt and GFAP by immunohistochemistry. Results On day 1,the basic PWL and % MPE of six groups had no significant difference. On day 7,the basic PWL had no marked difference among the six groups,while compared with group Ⅰ,the % MPE of groupⅡ,Ⅳ,Ⅴ and Ⅵ decreased( P 0. 05); compared with groupⅡ,the % MPE of groupⅢ,Ⅴ and Ⅵincreased( P 0. 05). On day 7,there was no significant difference in the expression of ERK in L5 spinal cord among six groups. However,compared with groupⅠ,the expression of p-ERK in groupⅡ,Ⅳ and Ⅵwas obviously increased( P 0. 05). Compared with groupⅡ,the expression of p-ERK in group Ⅲ,Ⅳ,Ⅴand Ⅵ was markedly decreased( P 0. 05). Compared with groupⅠ,the expression of GFAP in groupⅡ andⅣ was obviously increased( P 0. 05); compared with groupⅡ,the expression of GFAP in groupⅢ,ⅤandⅥwas markedly decreased( P 0. 05). Conclusion Dexmedetomidine can partially prevent the development of morphine tolerance in normal rats possibly by the inhibition of phosphorylation of ERK and the activation of astrocytes in the spinal cord.