Role Of Estrogen In The Pain Modulation Of Ovariectomized Mice

Gender differences in pain perception have been demonstrated in clinical studies and animal experiments. Estrogen actions now are recognized to occur via two distinct estrogen receptors (ER), ERαand ERβare widely distributed in the CNS region related to pain modulation. These anatomical structure indicate estrogen acts on ER to modulate pain perception, whereas the underlying mechanism is still in question. Here we mainly explore the possible effect and pathway of estrogen modulating pain through intermittent neuron activation in the dorsal spinal cord, pain afferent fibers and astrocytes activation.The effects of estrogen on pain threshold was evaluated with immunohistochemitry and pain behaviour test and pain score in ovariectomized C57B/L6 mice following estrogen intraperitoneal injections. The pain mice model was established by injecting formalin into the right hind paw, C57B/L6 mice were randomized into four groups : control group ( intact mice), Sham group , Vehicle group (ovariectomized mice with sesame oil ip injections)and Estrogen group(ovariectomized mice with 17β-estradiol ip injections). The effects of neuronal activation and pain afferent fibers in the dorsal horn of spinal cord were investigated by measurement of pain score and immunohistochemistry examination of c-Fos, substance P, glial fibrillary acidic protein(GFAP), Calbindin and Calretinin at L3-L5 level of spinal cord. The results were as follows:1. The measurement of thermal withdrawal latency (TWL) and hotplate latency in ovariectomized mice for continous five days showed that shortened latency, decreased pain threshold and increased pain hyperalgesia in ovariectomized mice comapared with control mice.2. The inflammatory pain mice model was established by injecting formalin into the right hind paw, two phase of pain behaviour was charateristics of pain model induced by formalin. There is no significant difference in first-phase pain score of mice following formalin stimulation from control group, Sham group,OVX+V group and OVX+E group(P>0.05). Pain score in the intermittent and early stage of secondary phase was increased significantly in the mice of OVX+V group following formalin stimulation compared to control,Sham and OVX+E group(P<0.05).3. The increased expression of c-Fos-like immunoreactivity neuron (FLIN) ,substance P and GFAP immunoreactivity and decreased expression of calbindin and calretinin in dorsal horn of the spinal cord was observed in the ovariectimized mice followed by formalin injection in the hind paw compared to control mice, which can be reversed by estrogen effectively.The aboved results suggest that estrogen produced analgesic effect in ovariectomized mice maybe mediate through modulating sensory neurons and afferent fibers in the superficial dorsal horn of the spinal cord.