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.