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Colocalization of oestrogen receptor immunoreactivity and preproenkephalin mRNA expression fo neurons in the superficial laminae of the spinal and medullary dorsal horn of rats
Klin o experimentell medicin.
1996 (English)In: Eur J Neurosci, Vol. 8, no 11, 2240-2245 p.Article in journal (Refereed) Published
Abstract [en]

A double-labelling procedure combining immunohistochemical staining with in situ hybridization using a radiolabelled cRNA probe was employed to demonstrate oestrogen receptor-like immunoreactivity and preproenkephalin-A mRNA in the medullary and spinal dorsal horn of female rats. Both markers labelled large numbers of neurons in the substantia gelatinosa and its trigeminal homologue. Many of these neurons were double-labelled, displaying both oestrogen receptor-like-immunoreactivity and preproenkephalin-A mRNA; cell counts showed that 40-60% of the of the oestrogen receptor-like-immunoreactive cells in the superficial laminae also were labelled for preproenkephalin-A mRNA, and that 60-70% of the preproenkephalin-A mRNA-labelled neurons in the same laminae displayed oestrogen receptor-like immunoreactivity. Previous studies have shown that oestrogen receptors can bind to the promoter region of the preproenkephalin-A gene, and studies on the hypothalamus have demonstrated that oestrogen regulates enkephalin expression in select neuronal populations. The present results demonstrate that enkephalinergic neurons in the superficial dorsal horn contain oestrogen receptors and suggest that oestrogen may play an important role in the modulation of sensory and nociceptive processing in the lower medulla and spinal cord.

Place, publisher, year, edition, pages
1996. Vol. 8, no 11, 2240-2245 p.
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-125106PubMedID: 8950107OAI: oai:DiVA.org:uu-125106DiVA: diva2:318387
Available from: 2010-05-07 Created: 2010-05-07 Last updated: 2014-05-20Bibliographically approved
In thesis
1. Estrogen receptor expression in relation to pain modulation and transmission: experimental studies in rats
Open this publication in new window or tab >>Estrogen receptor expression in relation to pain modulation and transmission: experimental studies in rats
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

Estrogens have a remarkably wide range of actions in the mammalian brain. They not only play a pivotal role in reproductive behavior and sexual differentiation, but also contribute to e.g. thermoregulation, feeding, memory, neuronal survival and the perception of somatosensory stimuli. A multitude of studies on both animals and human subjects has demonstrated 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 therefore need to be evaluated specifically in relation to the localization and intrinsic characteristics of the neurons engaged. The overall aim of this thesis is to gain specific knowledge of the possible cellular mechanisms by which estrogens may influence the transmission of nociceptive stimuli at the level of the spinal cord.

The estrogen receptors, by which estrogens regulate non-genomic as well as genomic mechanisms, are crucial to estrogen signaling in general and essential to the estrogen-induced effects in the brain. In Paper I, we use immunohistochemistry to label neurons containing estrogen receptor-! (ERα) in the medullary and spinal dorsal horn of female rats. Large numbers of ER!-expressing neurons were found in lamina I and lamina II, i.e. in the areas involved in the processing of primary afferent nociceptive information. This distribution in part overlaps that of enkephalin, a potent pain-inhibiting endogenous opioid. The effects of gonadal hormones on pain modulation may, to a great extent, be blocked by the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in the prosecution of hormonal pain regulation. By combining immunohistochemical labeling of ERα with in situ hybridization of preproenkephalin mRNA (Paper II), we demonstrate that the majority of enkephalinergic neurons in the superficial laminae of the spinal and medullary dorsal horn express ER!. This co-localization and the fact that the preproenkephalin gene contains a sequence that binds ERs, suggest that estrogens may potentially regulate enkephalin expression in these cells. This is further supported by the findings in Paper III in which we show that a single subcutaneous injection of estradiol induces a significant increase (on average 68%) in preproenkephalin mRNA content in the spinal cord after 4 hours. The expression of the enkephalin gene in the spinal cord is thus sensitive to fluctuating estradiol levels. In Paper IV, a noxious injection of formalin is used to induce activation of a neuronal population involved in nociceptive transmission from the face. By using a dual-labeling immunohistochemistry protocol, we were able to identify ER!-expressing cells within this neuronal population suggesting that nociceptive-responsive neurons in the medullary dorsal horn express ER!. In all, our findings provide morphological as well as biochemical evidence in support for an estrogen-dependent modulation of nociceptive processing at the level of the dorsal horn.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 90 p.
Series
Linköping University medical dissertation, ISSN 0345-0082 ; 1122
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:uu:diva-125111 (URN)978-91-7393-644-6 (ISBN)
Public defence
2009-05-26, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2011-03-04 Created: 2010-05-07 Last updated: 2011-03-04Bibliographically approved

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