The long-range goal of the proposed research is to improve understanding of the neural mechanisms of gynecological pain. The studies use behavioral and electrophysiological methods to characterize escape behaviors and CNS activity elicited by pelvic organ stimulation in female rats under various normal and pathological conditions.
Specific aims for the next 5 years focus on mechanisms of vaginal hyperalgesia (VAGH) and will test three hypotheses. (1) Reproductive senescence and VAGH: Vaginal sensitivity in women increases after menopause to produce VAGH. This VAGH is thought to be due to the effects of estrogen loss on vaginal tissue. The hypothesis that senescence-VAGH is associated with hypoestrogenic-conditions and changes in physical properties of the vagina will be tested in rats by using behavioral methods in awake rats to study how escape responses to vaginal distension and how vaginal tone both changes as the rats age through senescence and following hormonal manipulations. (2) Endometriosis and VAGH: Viable endometrial tissue outside the uterus in women is associated with infertility and pelvic pain, including VAGH. Because estrogen is necessary for ectopic endometrial viability, behavioral methods and hormonal manipulations will be used on a rat model of endometriosis to test the hypothesis that endometriosis-VAGH, in contrast to senescence-VAGH, depends upon estrogen and is independent of vaginal tone. (3) CNS mechanisms: Despite the fact that sensory afferents of the rat female reproductive tract convey highly specific and topographically-organized information to the CNS, many neurons in the spinal cord and thalamus respond convergently to stimulation of pelvic organs and skin, and the responses can change depending on changing CNS control factors. Even more surprisingly, this situation appears also to apply to neurons in the two other ports-of-entry for pelvic information to the CNS, the gracile and solitary nuclei, suggesting that these two portal nuclei warrant inclusion, along with the spinal cord, in studies of CNS pain mechanisms. Accordingly, electrophysiological studies will compare how responses to stimulation of pelvic organs and skin by neurons in the gracile and solitary nuclei, as well as in the spinal cord, change as a consequence of estrous state, senescence-VAGH, and endometrious-VAGH.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS011892-24
Application #
6186932
Study Section
Special Emphasis Panel (ZRG2-BPO (01))
Program Officer
Porter, Linda L
Project Start
1977-09-14
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2003-06-30
Support Year
24
Fiscal Year
2000
Total Cost
$230,853
Indirect Cost
Name
Florida State University
Department
Psychology
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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