Estrogen receptor-like immunoreactivity in the medullary and spinal dorsal horn of the female rat

doi:10.1016/0304-3940(95)11828-K

Neuroscience Letters

Volume 196, Issues 1–2, 18 August 1995, Pages 25-28

https://doi.org/10.1016/0304-3940(95)11828-K Get rights and content

Abstract

Using an immunohistochemical technique, we demonstrate that large numbers of neurons in the laminar spinal trigeminal nucleus and spinal gray matter of the female rat express estrogen receptors (ER). Densely packed ER-immunoreactive neurons were present in lamina II, but labeled neurons were also present in lamina I, the neck of the dorsal horn, and in lamina X. Labeling was present throughout the length of the spinal cord, with the exception of segments caudal to S1, which were unlabeled. The distribution of ER-containing neurons to areas that are involved in processing of primary afferent nociceptive information suggests that the pain modulatory effects of estrogen may be exerted at the spinal level.

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Morphine further leads to the activation of voltage-gated potassium channels at the presynaptic terminals (Vaughan et al., 1997), to the activation of postsynaptic GIRK channels (G protein-activated inwardly rectifying K+ channels), to the activation of TREK-1 potassium channels (Devilliers et al., 2013; Ocaña et al., 2004) and to the release of the inhibitory neurotransmitter GABA (Vaughan et al., 1997). Estrogen receptors are expressed in several brain regions involved in pain perception and modulation, such as the PAG, amygdala and spinal cord dorsal horn (Amandusson et al., 1995). Females show morphine efficacy at doses two to three times higher than males, and sex hormones seem to play a major role in this sexually dimorphic response (Cepeda and Carr, 2003; Krzanowska and Bodnar, 1999; Loyd et al., 2008; Posillico et al., 2015; Rosen et al., 2019; Wang et al., 2006).
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Most chronic noncancer pain (CNCP) conditions are more common in women and have been reported to worsen, particularly during the peak reproductive years. This phenomenon suggests that ovarian hormones might play a role in modulating CNCP pain. To this end, we reviewed human literature aiming to assess the potential role of ovarian hormones in modulating the following CNCP conditions: musculoskeletal pain, migraine headache, temporal mandibular disorder, and pelvic pain. We found 50 relevant clinical studies, the majority of which demonstrated a correlation between hormone changes or treatments and pain intensity, threshold, or symptoms. Taken together, the findings suggest that changes in hormonal levels may well play a role in modulating the severity of CNCP conditions. However, the lack of consistency in study design, methodology, and interpretation of menstrual cycle phases impedes comparison between the studies. Thus, while the literature is highly suggestive of the role of ovarian hormones in modulating CNCP conditions, serious confounds impede a definitive understanding for most conditions except menstrual migraine and endometriosis. It may be that these inconsistencies and the resulting lack of clarity have contributed to the failure of hormonal effects being translated into medical practice for treatment of CNCP conditions.
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Citation Excerpt :
Since the basal expression of ERα mRNA and protein is low in the rat spinal cord as compared to that of certain hypothalamic regions, for example (Simerly et al., 1990), applying different methods of enhancing labeling to increase sensitivity is often required. More recent studies using immunohistochemistry have shown a large amount of ERα-expressing neurons in the superficial laminae of the spinal and trigeminal dorsal horn of the rat (Amandusson et al., 1995; Vanderhorst et al., 2005; Williams and Papka, 1996) (Fig. 4A and B). The labeling of these cells was predominantly nuclear, and they were seen throughout the spinal cord, i.e. in cervical, thoracic, lumbar and sacral segments.
Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

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View full text

Estrogen receptor-like immunoreactivity in the medullary and spinal dorsal horn of the female rat

Abstract

Trends Neurosci.

Physiol. Behav.

Brain Res.

J. Steroid Biochem.

Endogenous opioidimmunoreactive neurons of the ventromedial hypothalamic nucleus concentrate estrogen in male and female rats

J. Neurosci. Res.

Oestrogen receptors in the preoptico-hypothalamic continuum: immunohistochemical study of the distribution and cell density during induced oestrous cycle in ovariectomized ewe

J. Neuroendocrinol.

Localization of preproenkephalin mRNA in the rat brain and spinal cord by in situ hybridization

J. Comp. Neurol.

Estrogen suppresses μ-opioid- and GABAB-mediated hyperpolarization of hypothalamic arcuate neurons

J. Neurosci.

Triggering of lordosis reflex in female rats with somatosensory stimulation: quantitative determination of stimulus parameters

J. Neurophysiol.

Estrogen suppresses μ-opioid- and GABA_B-mediated hyperpolarization of hypothalamic arcuate neurons