Change in the expressionof phosphorylated synapsin I in spinal dorsal hornfollowing chronic morphine tolerance in rats

Abstract

：Objective To investigatethe change in the expression of phosphorylated synapsin Ⅰ in the spinal dorsal horn following chronic morphine tolerance in rats.MethodsForty-five 1-2 month old male SD rats weighing 150-180 g were randomly divided into 5groups(n = 9 each): group Ⅰ sham operation(group S);groupⅡ normal saline(group NS);group Ⅲ morphine(group M);group Ⅳ Ketamine(group K)and groupⅤ M+K.An intrathecal(IT)catheter was placed in thesubarachnoid space at L3,4 interspace in group Ⅱ-Ⅴ.Animals showing motor orsensory dysfunction after surgery were excluded.Three days after surgery NS 40 μl,morphine20μg,ketamine 30 μg and morphine 20 μg+ketamine 30 μgwere injected IT twice a day for 7 consecutive days in group Ⅱ,Ⅲ,Ⅳ and Ⅴ respectively.50% paw withdrawal threshold(PWT)to mechanicalstimulus and paw withdrawal latency(PWL)to noxious thermal stimulus were measuredbefore(T_0,baseline),on the 1st,3rd,5th and 7th day of IT drug administration(T_(1-4))andat 1 day after IT drug administration(T_5).The animals were sacrificed after last painthreshold measurement.The lumbar segment(L_(3-6))was removed for determination of theexpression of phosphorylated synapsin Ⅰprotein.ResultsIn group M,PWT to mechanical stimulus was increased at T_(1,2),returned to the baselinelevel at T,and decreased at T_(4,5),and PWL to noxious thermal stimulus was prolonged atT_(1-3),returned to the baseline level at T_4 and shortened at T_5 as compared to thebaseline value at T_0indicating successful establishment of morphine tolerance.In groupM+K,PWT to mechanical stimulus was increased and PWL to noxious thermal stimulus wasprolonged at T_(1-5) as compared to the baseline value,indicating inhibition of morphinetolerance by ketamine.The expression of phospberylatod synapsin(Ser 603)was significantlyhigher in group M and M+K than in group S,and was significantly lower in group M+K than ingroup M.Conclusion The phosphorylated synapsin Ⅰ in the spinal dorsal horn may be involved in thedevelopment of chronic morphine tolerance which is partly mediated by NMDA receptor. Key words: Morphine; Drug tolerance; Spinal cord; Synaptophysin