Abstract
The estrogenic regulation of nociception can occur in multiple central areas including the dorsal horn of the spinal cord and various nuclei of the hindbrain that express estrogen receptors and where specific reactions to nociceptive stimuli have been observed. In Japanese quail, the estrogen-synthesizing enzyme, aromatase, is expressed in numerous neurons throughout the rostrocaudal extent of the spinal dorsal horn and in sensory and integrating nuclei in the hindbrain. We thus initiated a research program to assess the presence and function of aromatase in spinal and hindbrain areas involved in nociception in mammals. Numerous aromatase-immunoreactive fibers bearing varicosities were previously observed in the rat spinal cord. We demonstrate here the presence in the rat brainstem of aromatase immunoreactivity in sensory (trigeminal, solitary tract) and integrating (parabrachial, raphe) nuclei that are homologous to those expressing aromatase in quail. Despite this overall similarity, a striking difference was found at the cellular level: both perikarya and fibers were labeled in quail while only fibers were immunoreactive in rats. Recent behavioral studies in quail indicate that spinal aromatase produces estrogens that decrease the foot withdrawal latency to a painful thermal stimulus within 1 minute. Similarly, an intrathecal injection of 17β-estradiol (100 nM) in gonadally-intact male rats reduces the foot withdrawal latency to a painful thermal stimulus within 5 minutes. Together, these data strongly suggest the existence of a well-conserved rapid regulation of nociception that depends on the local synthesis of estrogens. Whether the rapid effect of endogenous estrogens on nociception in rat relies, like in quail, on spinal aromatization is currently under investigation.
