Objective To observe the accumulative analgesic effect of electroacupuncture(EA)and the simultaneous changes of protein kinase A(PKA) expression in hypothalamus and hippocampus in rats with chronic constrictive injury(CCI) or/and learning-memory impairment.Methods Sixty-eight female Wistar rats were randomized into normal control

CCI

CCI+EA 2 d

CCI+EA 2 w

OVX+CCI

OVX+CCI+EA 2 d and OVX+CCI+EA 2 w groups

with 10 cases in each except OVX+CCI group(n=8).CCI pain model was established by ligature of the right sciatic nerve with surgical suture.EA(2/15 Hz

1-2 mA

30 min) was daily applied to bilateral "Zusanli"(ST 36) and "Yanglingquan"(GB 34) for 2 days(2 d) and 2 weeks(2 w) respectively.Neuro-memory impairment was induced by OVX plus subcutaneous injection of D-galactose.Hyperalgesic scores(HS) were detected with radiation-heat irradiation and PKA activity was detected by immunohistochemical method.Results After CCI

HS of all groups increased significantly in comparison with normal control group(P<0.05).In simple CCI rats

compared with CCI group

HS of both CCI+EA 2 d and CCI+EA 2 w groups decreased markedly(P<0.05)

and that of CCI+EA 2 w group was evidently lower than that of CCI+EA 2 d group on the 18th day after CCI(P<0.05).In memory impairment rats

HS of both OVX+CCI+EA 2 d and OVX+CCI+EA 2 w groups was significantly lower than that of OVX+CCI group(P<0.05);and no significant difference was found between OVX+CCI+EA 2 w and OVX+CCI+EA 2 d groups in HS(P>0.05).Results of immunohistochemistry showed that the integral grey values(IGV) of PKA of paraventricular nucleus(PVN)

arcuate nucleus(ARC) and supraoptic nucleus(SON) of hypothalamus in CCI+EA 2 w group were significantly lower than those in normal control and CCI+EA 2 d groups(P<0.05).IGV of PVN and SON in OVX+CCI+EA 2 w group were also markedly lower than those in OVX+CCI group(P<0.05)

displaying upregulation and cumulative increase of PKA expression by EA 2 w.IGV of PKA

ARC and SON in OVX+CCI+EA 2 w group were markedly higher than those in CCI+EA 2 w group(P<0.05)

suggesting an apparent attenuation of the cumulative upregulation effect of PKA expression after learning-memory injury.The changing tendency of PKA expression in hippocampal CA1 region was similar to that of SON after repeated EA of ST36 and GB34.Conclusion Repeated EA has a cumulative analgesic effect in CCI rats

which is probably related to its resultant upregulation of PKA expression in neurons of hypothalamus and hippocampus and the animals' neuro-memory.