The role of gonadal hormones in mediating intracellular cascades in response to persistent /inflammatory nociceptive input.
Item
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Title
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The role of gonadal hormones in mediating intracellular cascades in response to persistent /inflammatory nociceptive input.
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Identifier
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AAI3187360
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identifier
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3187360
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Creator
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Kuba, Tzipora.
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Contributor
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Adviser: Vanya Quinones-Jenab
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Date
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2005
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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 found sex-specific differences in the discrimination and perception of nociceptive stimuli. The emerging picture from both clinical and preclinical studies suggests that the basis of these differences in nociceptive responses to such stimuli resides in the regulatory activity of gonadal hormones in the central nervous system. Published reports suggest that pain management targeted at female patients should consider hormonal factors during the female reproductive cycle.;We found that sex differences lie in the behavioral responses to persistent/inflammatory pain. Furthermore, gonadectomy of males and females alter corticosterone responses to formalin administration. However, although no differences were found in cyclooxygenase protein expression, we did find differences in prostaglandin serum levels between intact and gonadectomized animals. These findings indicate a possible mechanism in which corticosterone and/or endogenous gonadal hormones may modulate inflammatory pain responses through cyclooxygenase activation rather than transcriptional/translational effects.;We further demonstrated that estrogen and progesterone differentially mediate responses to formalin administration. While estrogen attenuates formal in-induced flinching during Phase II, progesterone attenuates Phase I activity. When co-administered, progesterone blocks estrogen-induced attenuation in Phase II. However, estrogen does not interfere with progesterone's activity in Phase I; suggesting that progesterone effects are independent from estrogen effects.;The administration of tamoxifen, a selective estrogen receptor modulator, resulted in the same Phase II attenuation as estradiol, while alpha-estradiol did not. These results indicate a genomic mechanism of action in which activation of intracellular estrogen receptors are required. Although both estrogen and progesterone receptors are present in the lumbo sacral region of the spinal cord, hormone replacement did not alter their levels. These indicate mechanisms further downstream than protein synthesis and or degradation mediating these effects. Furthermore, we demonstrate that with sustained release of hormone, via subcutaneous pellets rather than injection, estradiol exerts an anti-inflammatory action evident with 5% formalin and not with 1% formalin. Thus, suggesting that estrogen may be exerting its actions on inflammatory responses at the peripheral level of the nervous system. Since alpha-estradiol did not result in the same effect, we conclude that the anti-inflammatory activity is steroid receptor mediated. Because gonadal hormones differentially affect neural centers and are likely to play an important role in the expression and maintenance of pain states, females seeking pain management should consider hormonal factors during the female reproductive cycle.
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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.
