It is widely believed that pain affects men and women differentially; females demonstrate significantly higher? behavioral responses to chronic and inflammatory pain than males. Sex differences in the experiences of? pain reside in part in intrinsic biological differences; i.e., changes in pain responses associated with? physiological fluctuations of gonadal hormones are indicative of a significant contribution of estrogen and? progesterone to the regulation of pain responses. We have recently shown that in female rats estrogen? produces a persistent analgesic effect on injury (inflammation)-induced pain. Our long-term goal is to? determine whether fluctuations during different stages of the female reproductive cycle in inflammatory and? persistent pain perception are due to fluctuations in estrogen. The objective of this proposal is to determine if? estrogen's analgesic effects on inflammatory/chronic pain are mediated through activation of inflammatory? mechanisms. Specifically, we hypothesize that estrogen's antihypera'nalgesic effects on injury? (inflammation)-induced pain are mediated through up-regulation of corticosterone release which in turn? down-regulates COX-2 protein activity and, thus, prostaglandin-biosynthesis. Studies addressing behavioral? responses to pain in females and the role of estrogen in persistent/inflammatory pain are limited.? Furthermore, although several publications have studied the effects of estrogen on COX-2 in ovarian tissue,? the role of estrogen in the regulation of prostaglandin release in the peripheral and central nervous system? has been little studied.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Kiprowska, Magdalena J; Stepanova, Anna; Todaro, Dustin R et al. (2017) Neurotoxic mechanisms by which the USP14 inhibitor IU1 depletes ubiquitinated proteins and Tau in rat cerebral cortical neurons: Relevance to Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis 1863:1157-1170
He, Huifang; Deng, Kangwen; Siddiq, Mustafa M et al. (2016) Cyclic AMP and Polyamines Overcome Inhibition by Myelin-Associated Glycoprotein through eIF5A-Mediated Increases in p35 Expression and Activation of Cdk5. J Neurosci 36:3079-91
Siddiq, Mustafa M; Hannila, Sari S; Carmel, Jason B et al. (2015) Metallothionein-I/II Promotes Axonal Regeneration in the Central Nervous System. J Biol Chem 290:16343-56
Shivers, Kai-Yvonne; Nikolopoulou, Anastasia; Machlovi, Saima Ishaq et al. (2014) PACAP27 prevents Parkinson-like neuronal loss and motor deficits but not microglia activation induced by prostaglandin J2. Biochim Biophys Acta 1842:1707-19
Huang, Qian; Wang, Hu; Perry, Seth W et al. (2013) Negative regulation of 26S proteasome stability via calpain-mediated cleavage of Rpn10 subunit upon mitochondrial dysfunction in neurons. J Biol Chem 288:12161-74
Huang, He; Wang, Hu; Figueiredo-Pereira, Maria E (2013) Regulating the ubiquitin/proteasome pathway via cAMP-signaling: neuroprotective potential. Cell Biochem Biophys 67:55-66
Hannila, Sari S; Siddiq, Mustafa M; Carmel, Jason B et al. (2013) Secretory leukocyte protease inhibitor reverses inhibition by CNS myelin, promotes regeneration in the optic nerve, and suppresses expression of the transforming growth factor-? signaling protein Smad2. J Neurosci 33:5138-51
Myeku, Natura; Wang, Hu; Figueiredo-Pereira, Maria E (2012) cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons. Neurosci Lett 527:126-31
Metcalfe, M J; Huang, Q; Figueiredo-Pereira, M E (2012) Coordination between proteasome impairment and caspase activation leading to TAU pathology: neuroprotection by cAMP. Cell Death Dis 3:e326
Myeku, Natura; Figueiredo-Pereira, Maria E (2011) Dynamics of the degradation of ubiquitinated proteins by proteasomes and autophagy: association with sequestosome 1/p62. J Biol Chem 286:22426-40

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