The effects of estrogen on cytokine levels before and during inflammatory pain in female rats
Item
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Title
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The effects of estrogen on cytokine levels before and during inflammatory pain in female rats
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Identifier
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d_2009_2013:2645416c2007:10407
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identifier
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10468
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Creator
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Shivers, Kai-Yvonne,
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Contributor
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Vanya Quinones-Jenab
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Date
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2009
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychobiology | Experimental psychology | Cytokine | Estrogen | Inflammation | Pain | Rat
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Abstract
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Epidemiological studies demonstrate that sex differences exist in pain perception and discrimination; females display greater sensitivity to noxious stimuli than males. Additionally, the female endocrinological profile is also shown to alter nociceptive responses to pain. For instance, 17beta-estradiol reduces flinching responses after formalin administration. Furthermore, nociceptive responses to formalin are reduced during the proestrus stage of the estrous cycle. However, little is known about the specific biochemical mechanisms involved in estrogen's anti-hyperalgesic responses to pain. Research demonstrates that proinflammatory cytokines play a principal role in initiating pain responses. Cytokines activate cyclooxygenase (COX)-dependent prostanoid release. Additionally, glucocorticoids (i.e. corticosterone) are postulated to inhibit prostaglandin activation, and thus hamper inflammatory responses. The objective of this study is to determine if estrogen modulates inflammatory-induced pain by altering cytokine pathways and the hypothalamic-pituitary-adrenal (HPA) axis. Estrogen is postulated to hamper nociceptive responses by decreasing basal and inflammatory-induced cytokine levels at peripheral and central sites, and by increasing CORT activity. In intact female rats, hormone fluctuations across the estrous cycle led to changes in cytokine, but not CORT, levels. In most cases, serum cytokine levels were altered in naive rats, suggesting that in intact models the endocrinological profile influences pain responses by modulating cytokine levels before the introduction of painful stimuli. Following ovariectomy and/or adrenalectomy, 17beta-estradiol altered peripheral and central cytokine levels both before and following formalin-induced pain. Estradiol's effects worked independent of CORT release, since estradiol's alteration of cytokine levels were also shown in adrenalectomized rats. Together, these results further suggest that estrogen's influence on cytokine levels contributes in part to anti-hyperalgesic effects within the formalin paradigm. Finally, 17beta-estradiol lowered nociceptive responding in ovariectomized rats as measured by increased paw withdrawal latencies before and following carrageenan-induced pain. 17beta-estradiol decreased paw inflammation and altered peripheral and central cytokine levels, which may be mechanisms through which estrogen lowers pain responses during the carrageenan paradigm. Although estradiol increased CORT levels in this model, heightened CORT activity did not always lead to a reduction in behavioral responses to pain. Taken together, our results suggest that estrogen's anti-hyperalgesic effects are mediated through down-regulation of the cytokine pathway in a mechanism independent of actions on the HPA axis.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Psychology
