• Xiaotang Fan, Hyun-Jin Kim, Margaret Warner, and Jan-Ake Gustafsson.
• Division of Medical Nutrition, Department of Biosciences and Nutrition, Karolinska Institute, Novum, SE-141 86 Stockholm, Sweden.
• Proc. Natl. Acad. Sci. U.S.A. 2007 Aug 21;104(34):13696-701.

AbstractEstrogen is known to influence pain, but the specific roles of the two estrogen receptors (ERs) in the spinal cord are unknown. In the present study, we have examined the expression of ERalpha and ERbeta in the spinal cord and have looked for defects in pain pathways in ERbeta knockout (ERbeta(-/-)) mice. In the spinal cords of 10-month-old WT mice, ERbeta-positive cells were localized in lamina II, whereas ERalpha-positive cells were mainly localized in lamina I. In ERbeta(-/-) mice, there were higher levels of calcitonin gene-regulated peptide and substance P in spinal cord dorsal horn and isolectin B4 in the dorsal root ganglion. In the superficial layers of the spinal cord, there was a decrease in the number of calretinin (CR)-positive neurons, and in the outer layer II, there was a loss of calbindin-positive interneurons. During embryogenesis, ERbeta was first detectable in the spinal cord at embryonic day 13.5 (E13.5), and ERalpha was first detectable at E15.5. During middle and later embryonic stages, ERbeta was abundantly expressed in the superficial layers of the dorsal horn. ERalpha was also expressed in the dorsal horn but was limited to fewer neurons. Double staining for ERbeta and CR showed that, in the superficial dorsal horn of WT neonates [postnatal day 0 (P0)], most CR neurons also expressed ERbeta. At this stage, few CR-positive cells were detected in the dorsal horn of ERbeta(-/-) mice. Taken together, these findings suggest that, early in embryogenesis, ERbeta is involved in dorsal horn morphogenesis and in sensory afferent fiber projections to the dorsal horn and that ERbeta is essential for survival of dorsal horn interneurons throughout life.

28 keywords...

hide…