The role of extracellular signal-regulated kinase signal pathway in the development of chronic morphine tolerance in rats
10.3760/cma.j.issn.0254-1416.2010.12.013
- VernacularTitle:胞外信号调节激酶信号通路在大鼠慢性吗啡耐受形成中的作用
- Author:
Meili ZHAI
;
Yi CHEN
;
Yonghao YU
- Publication Type:Journal Article
- Keywords:
Morphine;
Drug tolerance;
Extracellular signal-regulated kinase
- From:
Chinese Journal of Anesthesiology
2010;30(12):1449-1452
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of extracellular signal-regulated kinase(ERK)signal pathway in the spinal cord in the development of chronic morphine tolerance.Methods Thirty healthy male SD rats weighing 300-350 g in which intrathecal(IT)catheters were successfully implanted without complication were randomly divided into 3 groups(n = 10 each): group Ⅰ control(group C);group Ⅱ morphine tolerance(group M)and group Ⅲ morphine tolerance + PD98059(ERK upstream kinase MEK inhibitor)(group P).Morphine tolerance was induced with IT morphine 10 μg twice a day for 7 consecutive days.In group P PD98059 10 μg was injected IT at 30 min before each morphine administration.Tail flick latency(TFL)(the time between the onset of heat stimulus and voluntary tail withdrawal)was measured once a day at 30 min after first IT morphine administration and at 1 day after last IT morphine.Maximum analgesic effect(MPE)was calculated.MPE =(TFL after IT morphine - baseline TFL)/(12 - baseline TFL)× 100%.The animals were sacrificed after last TFL measurement.The L3-5 segment of the spinal cord was isolated for determination of the expression of μ-receptor and phosphorylated ERK 1/2(p-ERK1/2)by Western blot analysis and fluoroimmunoassay.Results Morphine tolerance was induced in group M and M + P.MPE was higher in group P than in group M.The expression of μ-receptor in spinal dorsal horn was significantly lower while the p-ERK1/2 expression was higher in group M than in group C.IT PD98059 significantly up-regulated μ-receptor expression and down-regulated p-ERK expression in group P as compared with group M.Conclusion ERK signal pathway is involved in the development of chronic morphine tolerance in rats.
