The long-term objective of the proposed research is to provide an increased understanding of the functions and organization of the afferent (sensory) innervation of female reproductive organs under normal and pathological conditions, with an emphasis on the neural mechanisms underlying pelvic pain. Using the rat as a model, parallel behavioral, electrophysiological and neuroanatomical studies are proposed. Behavioral studies will determine quantitatively the levels of mechanical stimulation of the uterus and vagina that the rat detects or finds aversive. Electro-physiological studies will examine the response properties of fibers in the pelvic and hypogastric nerves to these stimuli. Neuroanatomical studies wi)l use multiple tracing methods to characterize the topographic organization of inputs to the spinal cord arising from different components of each of the pelvic structures, with an emphasis on those from reproductive organs. Most studies will focus on the healthy rat, examining and comparing changes in behavioral and electrophysiological responses that occur as a function of estrous state, pregnancy and various experimentally-induced hormonal conditions. Additional similar studies will be carried out on a rat model for endometriosis and the results compared with those obtained from healthy rats. It is reasoned that improving knowledge of the relationship between the characteristics of afferent fibers supplying female reproductive organs and the sensory consequences of their stimulation under healthy and pathological conditions will not only improve understanding of basic mechanisms underlying the reproductive process, but also lead to improved strategies for treatment of disorders of the reproductive system, in particular for treatment of the pain that is a common component of such disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS011892-15A1
Application #
3394649
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1977-09-14
Project End
1992-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
15
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Florida State University
Department
Type
Schools of Arts and Sciences
DUNS #
020520466
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
McAllister, Stacy L; Giourgas, Barbra K; Faircloth, Elizabeth K et al. (2016) Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents. Mol Cell Endocrinol 437:120-129
McAllister, Stacy L; Dmitrieva, Natalia; Berkley, Karen J (2012) Sprouted innervation into uterine transplants contributes to the development of hyperalgesia in a rat model of endometriosis. PLoS One 7:e31758
Stratton, Pamela; Berkley, Karen J (2011) Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update 17:327-46
Dmitrieva, Natalia; Nagabukuro, Hiroshi; Resuehr, David et al. (2010) Endocannabinoid involvement in endometriosis. Pain 151:703-10
Berkley, Karen J (2009) Balancing nociception in cycling females. Pain 146:9-10
McAllister, Stacy L; McGinty, Kristina A; Resuehr, David et al. (2009) Endometriosis-induced vaginal hyperalgesia in the rat: role of the ectopic growths and their innervation. Pain 147:255-64
Dmitrieva, Natalia; Zhang, Guohua; Nagabukuro, Hiroshi (2008) Increased alpha1D adrenergic receptor activity and protein expression in the urinary bladder of aged rats. World J Urol 26:649-55
Zhang, Guohua; Dmitrieva, Natalia; Liu, Yan et al. (2008) Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat. Am J Physiol Regul Integr Comp Physiol 294:R162-71
Berkley, Karen J; McAllister, Stacy L; Accius, Briane E et al. (2007) Endometriosis-induced vaginal hyperalgesia in the rat: effect of estropause, ovariectomy, and estradiol replacement. Pain 132 Suppl 1:S150-9
Nagabukuro, Hiroshi; Berkley, Karen J (2007) Influence of endometriosis on visceromotor and cardiovascular responses induced by vaginal distention in the rat. Pain 132 Suppl 1:S96-103

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