Abstract: Objective · Giving the ovariectomized (OVX) mice exogenous estrogen replace therapy (ERT) so as to explore the inflammatory mechanism of estrogen in the pain modulation of OVX mice.  Methods · Twenty-four 12-week-old female C57BL/6J mice were randomized into three groups: sham group (S), ovariectomy+placebo group (P), ovariectomy+estrogen group (E). The ERT began from one week after OVX and last for four weeks. Paw withdraw threshold (PWT) and paw withdraw latency (PWL) were measured at one day before OVX, and three days, one week, two weeks, three weeks, four weeks and five weeks after OVX. Concentrations of inflammatory cytokines in serum were measured at three days and five weeks postoperatively. Five weeks after operation, the lumbar intumescentia of spinal cord was taken and the expression of p38 was analyzed by Western blotting.  Results · All the OVX mice’s PWTs or PWLs were decreased after operation compared with non-operation mice; PWTs and PWLs were significantly different from group S separately from one week and three days after OVX (P<0.01). The inflammatory cytokines of OVX mice were significantly higher than group S (both P<0.01) at three days after OVX. Western blotting results showed that the p38 of group P was significantly higher than that of group S after five weeks postoperatively (P<0.01). By receiving ERT, both PWTs and PWLs of group E increased slightly and were significantly different from group S (P<0.01) at four and five weeks after OVX. At five weeks after OVX, inflammatory cytokines of group E were significantly lower than group P (P<0.01) but still much higher than group S (P<0.01). Meanwhile the content of p38 in group E was less than that in group P (P<0.01). The p38 in group E was still more than group S, however it was no longer significantly different from group S (P>0.05).  Conclusion · Estrogen may reduce concentrations of inflammatory cytokines through the p38 MAPK pathway and plays an important role in the pain modulation of OVX mice.

Key words: estrogen, pain, inflammation, p38