The role of COX-1 and COX-2 on estradiol's anti -hyperalgesic effects on induced -inflammatory nociceptive responses.
Item
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Title
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The role of COX-1 and COX-2 on estradiol's anti -hyperalgesic effects on induced -inflammatory nociceptive responses.
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Identifier
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AAI3296919
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identifier
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3296919
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Creator
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Hunter, Deirtra.
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Contributor
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Advisers: Vanya Quinones-Jenab | Joseph Glick
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Date
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2008
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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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Psychology, Psychobiology
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Abstract
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Clinical and preclinical studies have demonstrated significant sex differences in the perception of inflammatory pain; females display higher nociceptive responses to inflammatory stimuli than male rats. Additionally, the complex endocrinological profile of females has been shown to impact their nociceptive responses. For example, estradiol reduces Phase II behavioral-nociceptive responses after formalin administration. However, little is known about the specific biological pathway(s) and/or mechanisms in which estradiol affects inflammatory pain responses. Current literature has established that cyclooxygenases and prostanoids are major pro-inflammatory mediators directly linked to inflammatory responses. Additionally, glucocorticoids, (i.e. corticosterone) negatively regulate inflammatory induced COX-2, resulting in attenuation of inflammatory responses. The objective of this study was to further understand how estradiol alters induced inflammatory responses by examining two physiological pathways (i.e. COX-1/COX-2 regulation of the prostanoid biosynthetic pathway and corticosterone regulation of the COX-1/COX-2 pathway) which may in part be responsible for these effects. Estradiol, IBU and NS398 but not SC560 were shown to significantly attenuate behavioral responses after formalin. Co-administration of estradiol and IBU or NS398 revealed an additive not potentiated increase in attenuating induced nociceptive behavioral responses suggesting that regulation of behavioral responses by estradiol may be occurring through a pathway independent of the COX-prostanoid biosynthetic pathway. Furthermore, estradiol significantly reduced induced-thermal hyperalgesia as measured by decreased paw withdrawal latencies before and after carrageenan administration. Similar to observations observed using the formalin assay, estradiol's effects in the presence of either COX-inhibitor were additive after carrageenan administration providing further support for estradiol's regulation of induced-inflammatory nociceptive responses through an alternate pathway independent of the COX-prostanoid biosynthetic pathway. Surprisingly, significant attenuation of PWL before carrageenan suggests that estradiol is also effective in significantly attenuating induced acute nociceptive as well as inflammatory behavioral responses. Finally, estradiol-treated ADX animals showed significantly reduced flinching behaviors compared to untreated animals after formalin administration suggesting that corticosterone is not a mandatory mediator through which estradiol operates to attenuate induced nociceptive behavioral responses. In summary, our results suggest that estradiol's anti-hyperalgesic effects are not likely mediated in part through downregulation of COX activity and/or levels nor corticosterone downregulation of the COX-prostanoid biosynthetic pathway. Finally, estradiol's anti-hyperalgesic effects can be extended to the carrageenan induced thermal hyperalgesic pa in model whereby estradiol was shown to significantly attenuate both induced acute and inflammatory nociceptive behavioral responses.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
