Estrogen receptor-α expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat

Estrogens exert a substantial influence on the transmission of nociceptive stimuli and the susceptibility to pain disorders as made evident by studies in both animals and human subjects. The estrogen receptor (ER) seems to be of crucial importance to the cellular mechanisms underlying such an influence. However, it has not been clarified whether nociceptive neurons activated by pain express ERs. In this study, a noxious injection of formalin was given into the lower lip of female rats, thereby activating nociceptive neurons in the trigeminal subnucleus caudalis as demonstrated by immunohistochemical labeling of Fos. Using a dual-label immunohistochemistry protocol ERα-containing cells were visualized in the same sections. In the superficial layers of the medullary dorsal horn, 12% of ERα-labeled cells, mainly located in lamina II, also expressed noxious-induced Fos. These findings show that nociceptive-responsive neurons in the medullary dorsal horn express ERα, thus providing a possible morphological basis for the hypothesis that estrogens directly regulate pain transmission at this level.