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  Estrogen controls PKCe-dependent mechanical hyperalgesia through direct action on nociceptive neurons

Hucho, T. B., Dina, O. A., Kuhn, J., & Levine, J. D. (2006). Estrogen controls PKCe-dependent mechanical hyperalgesia through direct action on nociceptive neurons. European Journal of Neuroscience: European Neuroscience Association, 24(2), 527-534. doi:10.1111/j.1460-9568.2006.04913.x.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8405-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8406-1
Genre: Journal Article
Alternative Title : Eur. J. Neurosci

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j.1460-9568.2006.04913.pdf (Any fulltext), 486KB
 
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Hucho, Tim B.1, Author              
Dina, Olayinka A., Author
Kuhn, Julia, Author
Levine, Jon D., Author
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1Signal Transduction in Mental Retardation and Pain (Tim Hucho), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479646              

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 Abstract: Protein kinase C epsilon (PKCε) is an important intracellular signaling molecule in primary afferent nociceptors, implicated in acute and chronic inflammatory as well as neuropathic pain. In behavioral experiments inflammatory mediators produce PKCε-dependent hyperalgesia only in male rats. The mechanism underlying this sexual dimorphism is unknown. We show that the hormone environment of female rats changes the nociceptive signaling in the peripheral sensory neuron. This change is maintained in culture also in the absence of a gender-simulating environment. Stimulation of β2-adrenergic receptors (β2-AR) leads to PKCε activation in cultured dorsal root ganglia (DRG) neurons derived from male but not from female rats. Addition of estrogen to male DRG neurons produces a switch to the female phenotype, namely abrogation of β2-AR-initiated activation of PKCε. Estrogen interferes downstream of the β2-AR with the signaling pathway leading from exchange protein activated by cAMP (Epac) to PKCε. The interfering action is fast indicating a transcriptional-independent mechanism. Estrogen has a dual effect on PKCε. If applied before β2-AR or Epac stimulation, estrogen abrogates the activation of PKCε. In contrast, estrogen applied alone leads to a brief translocation of PKCε. Also in vivo the activity of estrogen depends on the stimulation context. In male rats, intradermal injection of an Epac activator or estrogen alone induces mechanical hyperalgesia through a PKCε-dependent mechanism. In contrast, injection of estrogen preceding the activation of Epac completely abrogates the Epac-induced mechanical hyperalgesia. Our results suggest that gender differences in nociception do not reflect the use of generally different mechanisms. Instead, a common set of signaling pathways can be modulated by hormones.

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Language(s): eng - English
 Dates: 2006-07-01
 Publication Status: Published in print
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 Identifiers: eDoc: 307655
DOI: 10.1111/j.1460-9568.2006.04913.x
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Title: European Journal of Neuroscience : European Neuroscience Association
  Alternative Title : Eur. J. Neurosci
Source Genre: Journal
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Pages: - Volume / Issue: 24 (2) Sequence Number: - Start / End Page: 527 - 534 Identifier: ISSN: 1460-9568