FEMALE PELVIC PAIN, HORMONES,AND NEUROPLASTICITY
Peter G Smith, Director
University Of Kansas Medical Center, Msn 1039, Kansas City, Ks 66160
Grant 3R01HD049615-04S1 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Hormonal status and vaginal function are closely linked. Diminished reproductive hormones at menopause lead to vaginal atrophy and dryness. Menopause is often accompanied by dysesthetic vulvodynia, a pain syndrome consisting of burning and itching. Together with vulvar vestibulitis, an allodynia-like syndrome linked to early oral contraceptive use, vulvodynia represents an under-recognized but significant health problem, afflicting some 16% of the adult US female population. The etiology of these syndromes is poorly understood, although vulvar vestibulitis is associated with increased numbers of pain-sensing fibers. No animal models have been available to provide a better framework of understanding. Recently, we showed that estrogen regulates vaginal innervation in rats. Ovariectomy, which approximates human menopause, dramatically increases numbers of vaginal sensory nociceptors, as well as sympathetic and parasympathetic axons. We hypothesize that this is due to modulation of trophic factor release from vaginal tissues, and that altered innervation will influence key aspects of vaginal function, including blood flow, vascular permeability, and pain sensitivity. In aim 1 we propose to characterize the relationship between hormonal status and vaginal innervation in rats during the estrous cycle, pregnancy, and adult and juvenile hormone administration. We also determine if human vaginal innervation varies with hormonal state. Aim 2 assesses cellular mechanisms underlying axonal remodeling by determining effects of reproductive hormones on vaginal target tissue and on sensory and autonomic neurons. Aim 3 examines molecular mechanisms mediating vaginal remodeling by investigating expression and functional relevance of potential trophic factors. In aim 4, we assess the functional significance of vaginal nerve remodeling on blood flow, neurogenic inflammation and behavioral avoidance of painful stimuli. These studies are conducted using methods in cell biology, tissue culture, molecular biology, physiology, pharmacology and behavior. The findings of these experiments will provide insight into mechanisms underlying hormone-dependent remodeling of vaginal innervation, and whether altered innervation may contribute to vaginal dysfunction. Moreover, these studies will provide a better understanding of the relationship between vaginal nerve plasticity and vulvodynia, and potentially lead to new therapeuties aimed at reversing vaginal sensory hyperinnervation
Keywords: 21+ years old; Adolescent; Adolescent Youth; Adult; Animal Model; Animal Models and Related Studies; Atrophic; Atrophy; Autonomic ganglion; Axon; Behavior; Behavioral; Biological; Biopsy; Blood flow; Body Tissues; Burn injury; Burning Pain; Burning vulva; Burns; CGRP; CNS plasticity; Calcitonin Gene-Related Peptide; Caliber; Causality; Cell Body; Cellular biology; Change of Life, Female; Chemotherapy-Hormones/Steroids; Common Rat Strains; Contraceptive Usage; Contraceptives, Oral; Culture Media; DNA Molecular Biology; Diameter; Discomfort of Vulva; Disease; Disorder; Down-Regulation; Down-Regulation (Physiology); Downregulation; Dryness; Dysfunction; Endocrine Gland Secretion; Estrogen Receptors; Estrogenic Agents; Estrogenic Compounds; Estrogens; Estrous Cycle; Estrus; Etiology; External Genitalia; Female; Fiber; Functional disorder; Gene Expression; Gene Proteins; Genital; Genital System, Female, Vagina; Genital system; Gestation; Gonadal Steroid Hormones; Health; Hormonal; Hormones; Human; Human, Adult; Human, General; Immunoblotting; In Vitro; Insect Growth Regulators; Intervention; Intervention Strategies; Itching; Juvenile Hormones; Lead; Link; Mammals, Rats; Man (Taxonomy); Man, Modern; Mediating; Menopausal Syndrome; Menopause; Menopause Syndrome; Methods; Microarray Analysis; Microarray-Based Analysis; Molecular; Molecular Biology; Nerve; Nerve Cells; Nerve Unit; Nervous; Neural Cell; Neurites; Neurocyte; Neurogenic Inflammation; Neuronal Plasticity; Neurons; Neuropeptides; Nociceptors; Oophorectomy; Operation; Operative Procedures; Operative Surgical Procedures; Oral Contraceptives; Ovariectomy; Pain; Painful; Pains, Burning; Pb element; Pelvic Pain; Peripheral Nerves; Pharmacology; Physiology; Physiopathology; Population; Pregnancy; Protein Gene Products; Proteins; Pruritic Disorder; Pruritis; Pruritus; RT-PCR; RTPCR; Rat; Rattus; Response Latencies; Reverse Transcriptase Polymerase Chain Reaction; Role; Sensory; Sex Hormones; Sex Steroid Hormones; Stimulus; Surgical; Surgical Interventions; Surgical Procedure; Syndrome; Testing; Therapeutic Estrogen; Therapeutic Hormone; Tissues; Touch; Touch sensation; Vagina; Vaginal; Vascular Permeabilities; Vulva; Vulval discomfort; Vulvar discomfort; Vulvodynia; adult human (21+); allodynia; awake; behavior test; behavioral test; birth control pill; cell biology; cell body (neuron); contraceptive use; density; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; estrous; experiment; experimental research; experimental study; female gonadectomy; gene product; gonadal steroids; growth media; heavy metal Pb; heavy metal lead; innervation; insight; interventional strategy; juvenile; juvenile human; menopausal; microarray technology; model organism; nerve supply; neural cell body; neural mechanism; neural plasticity; neuromechanism; neuronal; neuronal cell body; neuroplasticity; new therapeutics; next generation therapeutics; novel therapeutics; pathophysiology; protein expression; release factor; reproductive; reproductive hormone; research study; reverse transcriptase PCR; sex steroid; social role; soma; surgery; tissue culture; urogenital system (genital part); vulvar vestibulitis
Project start date: 2009-09-30
Project end date: 2010-09-29
Budget start date: 30-SEP-2009
Budget end date: 29-SEP-2010
3R01HD049615-04S1 (2009): $72960
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Peter G Smith
Peter G Smith, Director
University Of Kansas Medical Center, Msn 1039, Kansas City, Ks 66160
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of the Outreach Core is to provide students on undergraduate campuses throughout Kansas with opportunities to become involved in and excited to pursue biomedical research as a profession. On these campuses, there is little specific focus; students major in biology, chemistry or, on some campuses, health related professions. Thus, outreach efforts are not specifically designed for trainees in cell and developmental biology. Programs described in the Progress Report and Undergraduate Support Core for the K-INBRE that we believe at this point to be successful are to be continued together with the Partnering Program, the purpose of which is to support travel and minor research related expenses for training, technology transfer, and collaboration among the Outreach Institutions (Haskell Indian Nations University, Washburn University, Fort Hays State University, Emporia State University, Pittsburg State University and Langston University) and Scientific Partner Hosts (KU Medical Center, KU Lawrence, Kansas State University, and Wichita State University) in specific areas of Cell and Developmental Biology
Keywords: Area; Biology; Biomedical Research; CRISP; Chemistry; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Developmental Cell Biology; Funding; Goals; Grant; Health; Institution; Investigators; Kansas; Medical center; Minor; NIH; National Institutes of Health; National Institutes of Health (U.S.); Programs (PT); Programs [Publication Type]; Progress Reports; Reports, Progress; Research; Research Personnel; Research Resources; Researchers; Resources; Science of Chemistry; Source; Students; Technology Transfer; Training; Travel; United States National Institutes of Health; Universities; Wichita; design; designing; outreach; programs
Project start date: 2009-05-01
Project end date: 2010-04-30
Budget start date: 1-MAY-2009
Budget end date: 30-APR-2010
PFA/PA: PAR-08-150
2P20RR016475-09_6359 (2009): $56189
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5P20RR016475-068015 from National Center For Research Resources IRG: ZRR1
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of the Kansas INBRE Bioinformatics Network is to serve the needs of investigators engaged in computationally intensive biomedical research, and to promote education in bioinformatics to students and researchers across the state of Kansas. To accomplish these goals the K-INBRE Bioinformatics Core has established and maintains a network of Bioinformatics Cores at the 4 major Kansas research institutions University of Kansas Medical Center, University of Kansas in Lawrence, Kansas State University, and Wichita State University. The specific aims of the Bioinformatics Core in the prior funding period were to 1) Provide support to research programs in traditional areas of genomic investigation, 2) Expand activities associated with high-throughput genomic analysis made possible through cDNA microarray technology, 3) Implement new approaches for acquiring, managing and analyzing large datasets in support of proteomic and lipidomic research activities, 4) Expand educational programs in bioinformatics at both graduate and undergraduate levels, including access by K-INBRE outreach institutions, and 5) Provide resources for high-end computational processing. By fulfilling these aims, the K-INBRE Bioinformatics Core will advance research programs of existing investigators, and contribute to the preparation of the next generation of biomedical researchers.
Project start date: 2006-05-01
Project end date: 2007-04-30
SYMPATHETIC NERVE REMODELING IN THE ADULT UTERUS
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01NS039570-04 from National Institute Of Neurological Disorders And Stroke IRG: ZRG1
Abstract: The objective of this application is to elucidate factors governing peripheral sympathetic nerve remodeling in the mature rodent uterus. Our published studies show that sympathetic nerve density of the virgin rat uterus fluctuates throughout the estrous cycle, a 4.5 day interval that is analogous to the human menstrual cycle. Nerve density is highest during diestrus and declines through estrus in association with rising plasma estrogen. Our preliminary experiments suggest that 1) NGF mRNA and protein are also reduced at estrus, 2) estrogen administration decreases sympathetic nerve density, and 3) mice lacking a functional estrogen receptor alpha have uteri that are grossly hyperinnervated. We hypothesize that rising plasma estrogen suppresses uterine neurotrophic factor production resulting in clinical sympathetic nerve degeneration followed by regeneration. The specific aims are 1) Characterize the structural changes in nerves occurring during the cyclical changes in uterine sympathetic innervation, 2) determine the estrous cycle hormonal factors that mediate changes in nerve density, 3) determine if uterine neurotrophic factors that induce sympathetic neuritogenesis vary during the estrous cycle 4) determine if exogenous estrogen or other hormones affect neurotrophin expression 5) determine if estrogen-mediated changes in sympathetic neuron neurotrophin receptor expression may also contribute to the neuroplasticity, 6) determine if antibodies that selectively block neurotrophin activity can prevent uterus-mediated sprouting in vitro, 7) determine the role of the estrogen receptor alpha on nerve and uterus using the ERKO mouse, and 8) assess the functional consequences of uterine sympathetic nerve remodeling. These aims will be accomplished using immunohistochemistry, in situ hybridization histochemistry, qualitative and quantitative RT-PCR, electron microscopy, enzyme-linked immunoassays, organ culture, and pharmacological analyses of neuroeffector transmission. These studies will provide new and important information on mechanisms underlying nerve remodeling in normal physiological conditions. This information may be important in advancing our understanding of the mechanisms regulating innervation in health and disease, and may have direct applicability to the understanding of dysmenorrhea and autonomic dysfunction that occurs in menopause.
Keywords: axon, hormone regulation /control mechanism, neural plasticity, neuroendocrine system, sympathetic nervous system, uterus, estrogen, estrogen receptor, estrus, menstrual cycle, myometrium, nerve growth factor, neuropharmacology, neurotrophic factor, receptor expression, electron microscopy, experimental brain lesion, immunocytochemistry, in situ hybridization, laboratory mouse, laboratory rat, mature animal, organ culture, transgenic animal
Project start date: 1999-12-01
Project end date: 2004-11-30
5R01NS039570-04 (2003): $243078
5R01NS039570-02 (2001): $229122
1R01NS039570-01 (2000): $222450
3R01NS039570-01S1 (2000): $50000
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01NS023502-04 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: Sympathetic innervation to Moller s smooth muscle in the superior eyelid of the rat normally is derived entirely from the ipsilateral sympathetic chain. Removal of the ipsilateral superior cervical ganglion (SCG) in juvenile and adult rats results in sustained SNS denervation and impairment of Moller s muscle adrenoceptor-mediated contractile response. In contrast, ganglionectomy in neonatal rats results in functional SNS reinnervation from the contralateral SCG. Contralateral reinnervation is beneficial, since contractile responses show less deficit and ptosis is markedly attenuated relative to older preparations in which reinnervation does not occur. The objectives of the present study are to characterize anatomical and physiological aspects of the contralateral projection, determine the cellular mechanisms responsible for enhanced neuroplasticity in neonatal rats and determine if contralkateral reinnervation occurs in other end organs. The specific aims of the project are to; 1) define the optimal age and time course for smooth muscle reinnervation, 2) determine the structural and functional correlates of contralateral reinnervation (LM histofluorescence and EM cytochemistry to assess density of innervation and neuro-muscular relationships; HRP transport to analyze numbers, size and distribution of ganglion cells; functional analysis of reflex contractile responses to selected stimuli), 3) determine effects on smooth muscle maturation using physiolgical/pharmacological methods to assess function and quantitative LM to analyze muscle volume and cell numbers, 4) determine effects of perturbations which may modify neonatal neuroplasticity, and 5) examine other end organs to determine if contralateral innervation following neonatal denervation is more widespread than realized. This study will attempt to ascertain the mechanism of enhanced neuroplasticity in the neonatal SNS which has not previously been studied. Furthermore, it will provide information of clinical relevance regarding possible amelioration or treatment of cervical SNS lesions (Horner s syndrome) for which adequate therapy does not exist.
Keywords: MUSCLE FUNCTION, MUSCLE CONTRACTION, MUSCLES, SMOOTH MUSCLE, NERVOUS SYSTEM AUTONOMIC, SYMPATHETIC NERVOUS SYSTEM, NERVOUS SYSTEM, NERVES, INNERVATION, NERVOUS SYSTEM, NEUROGLIA, NEUROPHYSIOLOGY, NEUROPLASTICITY, AGE (ANIMAL), INFANTS NEWBORN, NERVOUS SYSTEM AUTONOMIC, SUPERIOR CERVICAL GANGLION, NEUROBIOLOGY, DEVELOPMENTAL, NEUROMOTOR SYSTEM, NEUROMUSCULAR FUNCTION, NEUROSURGERY, DENERVATION, neuroanatomy, neuropharmacology, neurophysiology, ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, RATS (LABORATORY), BIOMEDICAL SYSTEMS AUTOMATED, COMPUTER PROCESSING OF LABORATORY DATA, HISTOCHEMISTRY AND CYTOCHEMISTRY, OPTICS, LIGHT EMISSION, FLUORESCENCE, neurosurgery
Project start date: 1987-06-01
Project end date: 1990-06-30
SYMPATHETIC NEUROPLASTICITY IN THE NEONATAL RAT
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01NS023502-03 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: Sympathetic innervation to Moller s smooth muscle in the superior eyelid of the rat normally is derived entirely from the ipsilateral sympathetic chain. Removal of the ipsilateral superior cervical ganglion (SCG) in juvenile and adult rats results in sustained SNS denervation and impairment of Moller s muscle adrenoceptor-mediated contractile response. In contrast, ganglionectomy in neonatal rats results in functional SNS reinnervation from the contralateral SCG. Contralateral reinnervation is beneficial, since contractile responses show less deficit and ptosis is markedly attenuated relative to older preparations in which reinnervation does not occur. The objectives of the present study are to characterize anatomical and physiological aspects of the contralateral projection, determine the cellular mechanisms responsible for enhanced neuroplasticity in neonatal rats and determine if contralkateral reinnervation occurs in other end organs. The specific aims of the project are to; 1) define the optimal age and time course for smooth muscle reinnervation, 2) determine the structural and functional correlates of contralateral reinnervation (LM histofluorescence and EM cytochemistry to assess density of innervation and neuro-muscular relationships; HRP transport to analyze numbers, size and distribution of ganglion cells; functional analysis of reflex contractile responses to selected stimuli), 3) determine effects on smooth muscle maturation using physiolgical/pharmacological methods to assess function and quantitative LM to analyze muscle volume and cell numbers, 4) determine effects of perturbations which may modify neonatal neuroplasticity, and 5) examine other end organs to determine if contralateral innervation following neonatal denervation is more widespread than realized. This study will attempt to ascertain the mechanism of enhanced neuroplasticity in the neonatal SNS which has not previously been studied. Furthermore, it will provide information of clinical relevance regarding possible amelioration or treatment of cervical SNS lesions (Horner s syndrome) for which adequate therapy does not exist.
Keywords: MUSCLE FUNCTION, MUSCLE CONTRACTION, MUSCLES, SMOOTH MUSCLE, NERVOUS SYSTEM AUTONOMIC, SYMPATHETIC NERVOUS SYSTEM, NERVOUS SYSTEM, NERVES, INNERVATION, NERVOUS SYSTEM, NEUROGLIA, NEUROPHYSIOLOGY, NEUROPLASTICITY, AGE (ANIMAL), INFANTS NEWBORN, NERVOUS SYSTEM AUTONOMIC, SUPERIOR CERVICAL GANGLION, NEUROBIOLOGY, DEVELOPMENTAL, NEUROMOTOR SYSTEM, NEUROMUSCULAR FUNCTION, NEUROSURGERY, DENERVATION, neuroanatomy, neuropharmacology, neurophysiology, ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, RATS (LABORATORY), BIOMEDICAL SYSTEMS AUTOMATED, COMPUTER PROCESSING OF LABORATORY DATA, HISTOCHEMISTRY AND CYTOCHEMISTRY, OPTICS, LIGHT EMISSION, FLUORESCENCE, neurosurgery
Project start date: 1987-06-01
Project end date: 1989-11-30
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01NS023502-08 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: Sympathetic innervation of orbital targets normally is derived solely from the ipsilateral chain. However, unilateral superior cervical ganglionectomy of neonatal but not of juvenile or adult rats results in formation of an atypical contralateral pathway. The hypothesis to be tested is that the contralateral pathway derives from sprouting of sympathetic nerves innervating the anterior cerebral artery, and that outgrowth is prevented in older animals by local factors within the pathway and targets. The objectives of this study are to characterize contralateral outgrowth, and to elucidate mechanisms underlying temporal constraints. Specific aims are to 1) determine the trajectory of outgrowth by a) immunohistochemical localization of endogenous markers (DBH, NPY), b) visualization of exogenous, anterogradely transported markers (WGA-HRP and/or DiI or 3H-leucine), and c) electrical stimulation of the presumptive intracranial pathways while recording target muscle contractions; 2) determine the derivation and target distributions of sprouting fibers by a) double labelling of cerebro-vascular and orbital structures (retrograde transport of Fluoro-Gold, RITC), and b) examining cerebro-vascular targets for the presence of varicosities of neurons labelled retrogradely by WGA-HRP injections of orbital target; 3) assess the role of competition with heterologous innervation in restricting outgrowth by a) parasympathetic denervation (pterygopalatine and ciliary ganglionectomy), b) sensory denervation (capsaicin), and c) combined parasympathetic and sensory denervation; 4) determine if age-dependent changes in pathway and target tissues induce or inhibit reinnervation by examining a) rate and extent of sympathetic sprouting into intraocular transplants of cerebrovascular and orbital target, and b) age-dependent changes in molecular constituents (laminin, NGF, glycosaminoglycans); 5) establish the neuropeptide content of neurons projecting to the ipsilateral and contralateral orbital targets, and assess the functional consequences of reinnervation of nonvascular smooth muscle by NPY-containing neurons. The significance of this study is that it will 1) elucidate mechanisms of enhanced outgrowth which lead to functional recovery of denervated targets, and 2) determine functional consequences of target reinnervation by sympathetic nerves displaying non-native neuropeptide profiles.
Keywords: glia, innervation, muscle contraction, neural plasticity, smooth muscle, sympathetic nervous system, afferent nerve, axon, biomarker, cerebrovascular system, denervation, developmental neurobiology, electrostimulus, eye transplantation, laminin, neuroanatomy, neuropeptide, neurophysiology, neurotrophic factor, newborn animal, parasympathetic nervous system, superior cervical ganglion, computer processing of laboratory data, fluorescence, immunocytochemistry, laboratory rat
Project start date: 1987-06-01
Project end date: 1994-11-30
5R01NS023502-08 (1993): $161531
5R01NS023502-07 (1992): $155319
Sponsored Links Excellgen http://Excellgen.com
MECHANISMS OF SYMPATHETIC AXON PRUNING
Peter G Smith, Director
University Of Kansas Medical Center, Msn 1039, Kansas City, Ks 66160
Grant 5R01NS053796-04 from National Institute Of Neurological Disorders And Stroke
Abstract: Remodeling of mature neural pathways involves both axonal outgrowth to establish new connections and axonal degeneration whereby terminations are eliminated. Mechanisms by which axon terminations are eliminated, or pruned, in the absence of cell death are poorly understood. Peripheral sympathetic innervation presents an especially tractable model for studying axon pruning under normal physiological and pathophysiological conditions. Sympathetic axon density in the virgin rodent uterus fluctuates rapidly during the estrous cycle, with terminal axons degenerating when estrogen levels rise and regenerating when they decline. We have shown that estrogen elevates uterine brain derived neurotrophic factor, and hypothesize that this contributes to sympathetic axon degeneration. We hypothesize that brain derived neurotrophic factor activates the p75 neurotrophin receptor, which stimulates intra-axonal ceramide formation. This promotes terminal axon degeneration through abnormal increases in membrane permeability and actin depolymerization. The present study investigates mechanisms whereby targets elicit selective terminal axon pruning. The first aim evaluates the hypothesis that p75NTR activation is responsible for inducing sympathetic axon degeneration under physiological conditions. In aim 2, we explore the hypothesis that p75NTR activation produces axon degeneration by increasing permeability of axonal membranes, and by promoting destabilization of the actin cytoskeleton. In aim 3, we investigate the nature of ligands produced by the target that incur axon degeneration. Specifically, the roles of BDNF, pro-NGF and neurotrimin will be assessed. These studies use tractable in vivo and in vitro approaches to explore relationships among target- derived ligands, neural receptors, and signal transduction pathways, and will provide novel information on how selective terminal axon degeneration is accomplished under physiological and pathophysiological conditions. Findings will be pertinent to understanding both organizing principles related to normal nervous system plasticity, and to disturbances in innervation in certain disease states
Keywords: 21+ years old; Actins; Address; Adult; Axon; Axon Terminals; BDNF; Biological Models; Body Tissues; Brain-Derived Neurotrophic Factor; Cell Communication and Signaling; Cell Death; Cell Membrane Permeability; Cell Signaling; Cells; Cellular Matrix; Ceramide (lipids); Ceramides; Chimp; Chimpanzee; Coloring Agents; Common Rat Strains; Cytoskeletal System; Cytoskeleton; Diestrus; Disease; Disorder; Dyes; Estrogenic Agents; Estrogenic Compounds; Estrogens; Estrous Cycle; Event; Exclusion; GP80-LNGFR; Genital System, Female, Uterus; Horns; Human, Adult; In Vitro; Intracellular Communication and Signaling; Investigation; Ligands; MGC34632; Mammals, Rats; Mammals, Rodents; Mediating; Membrane; Messenger RNA; Mitochondria; Model System; Models, Biologic; Molecular; Muscle, Involuntary; Muscle, Smooth; Myometrial; NGF Receptor; NGFR; NGFR Protein; NRVS-SYS; Natural regeneration; Nature; Nerve; Nerve Endings, Presynaptic; Nerve Growth Factor Receptor p75; Nerve Growth Factor Receptor, Low-Affinity; Nerve Growth Factor Receptors; Nervous; Nervous System; Nervous system structure; Neural Pathways; Neurites; Neurologic Body System; Neurologic Organ System; Neuroreceptors; Neurotrophic Factor Receptor; Neurotropin Receptor p75; Pan; Pan Genus; Pan Species; Pathway interactions; Peripheral; Permeability; Phase; Phosphoprotein Phosphatase; Phosphoprotein Phosphatase-2C; Phosphoprotein Phosphohydrolase; Physiologic; Physiological; Presynaptic Terminals; Protein Phosphatase C; Protein Phosphatase-1; Protein Phosphatase-2A; Protein phosphatase; Proteins; RNA, Messenger; Rat; Rattus; Receptor Signaling; Receptor, Nerve Growth Factor; Receptors, NGF; Receptors, Nerve Growth Factor; Receptors, Neural; Receptors, Neurotrophin; Receptors, Sensory; Regeneration; Rodent; Rodentia; Rodentias; Role; Screening procedure; Sensory Receptors; Signal Transduction; Signal Transduction Pathway; Signal Transduction Systems; Signaling; Smooth muscle (tissue); Sphingomyelin Cholinephosphohydrolase; Sphingomyelin Cleaving Enzyme; Sphingomyelin Phosphodiesterase; Sphingomyelinase; Sphingomyelinase C; Study models; Synaptic Boutons; Synaptic Terminals; Therapeutic Estrogen; Tissues; Up-Regulation; Up-Regulation (Physiology); Upregulation; Uterine Muscle; Uterus; Work; adult human (21+); axonal degeneration; biological signal transduction; brain-derived neurotrophic factor precursor; cofilin; density; depolymerization; disease/disorder; gene product; gp75 NGFR; in vivo; innervation; insight; intracellular skeleton; mRNA; membrane permeability; membrane structure; mitochondrial; mitochondrial membrane; myometrium; necrocytosis; nerve supply; neurotrimin; neurotrophic factor; neurotrophin; neutrophin; novel; p75 neurotrophin receptor; p75(NTR); p75NTR; pathway; pro-BDNF; regenerate; screening; screenings; social role; womb
Project start date: 2007-02-01
Project end date: 2011-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
5R01NS053796-04 (2010): $318274
1R01NS053796-01A2 (2007): $321489
CONVERSION OF PARASYMPATHETIC FUNCTION AFTER INJURY
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01HD033025-02 from National Institute Of Child Health And Human Development IRG: NLS
Abstract: Peripheral nerve degeneration following injury has implications not only for the denervated target, but also for intact heterologous nerves. For example, sympathetic denervation causes changes in both structure and molecular phenotype of intact sensory and parasympathetic nerves projecting to a common target. Our preliminary studies show that heterologous nerve function can also be affected. Parasympathetic nerves innervating the rat superior tarsal muscle, an orbital smooth muscle, normally attenuate muscle contraction by inhibiting neurotransmission of excitatory sympathetic nerves. However, by 5 weeks after sympathectomy, parasympathetic nerves have become excitatory, eliciting a muscarinic cholinergic contraction; this is not attributable to muscle supersensitivity or diminished enzymatic degradation of acetylcholine, and is therefore believed to be due to changes occurring at the level of the nerve. Our objective is to determine mechanisms responsible for functional conversion, and its relevance to ameliorating deficits after nerve injury. hypothesizes that, as a result of sympathectomy, excitatory parasympathetic neuromuscular transmission is established because of increased neuroeffector contacts and/or increased transmitter production and release. further postulates that this occurs because of altered neurotrophic factor levels within the target, that it attenuates denervation- induced target deficits, and that it occurs in systems other than orbital smooth muscle. The specific aims are to further characterize parasympathetic functional conversion after sympathectomy by determining (1) its time course, (2) if it is associated with more intimate neuromuscular contacts, (3) if changes occur in numbers of parasympathetic fibers, and (4) whether it is accompanied by increased activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase. In addition, will determine (5) if it can be modulated by changing the availability of target-derived neurotrophic molecules, (6) if smooth muscle atrophy and supersensitivity are ameliorated, and (7) if functional conversion can be demonstrated in blood vessels of the eye and orbit. These studies investigate a novel and potentially important form of neuroplasticity. An understanding of this phenomenon will provide not only a clearer picture of its mechanism and prevalence, but also may give insight into how it can be manipulated to reverse denervation- induced target deficits, thus leading to improved medical rehabilitation strategies after nerve injury.
Keywords: injury, neural degeneration, neural plasticity, parasympathetic nervous system, sympathectomy, atrophy, blood vessel, denervation, neuroeffector, neuromuscular function, neuromuscular transmission, neuronal transport, neurotransmitter, neurotrophic factor, smooth muscle, antibody, electron microscopy, laboratory rat
Project start date: 1994-09-01
Project end date: 1999-08-31
5R01HD033025-02 (1995): $198161
1R01HD033025-01 (1994): $181977
5R01HD033025-05 (1998): $175979
5R01HD033025-04 (1997): $171296
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01NS023502-12 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Abstract: Investigator s ) Sympathetic nerves sprout aggressively in the neonatal animal, but show restricted outgrowth in the adult. Following excision of a superior cervical ganglion in the mature rat, smooth muscle of the orbit remains denervated indefinitely, while neonatally denervated targets are reinnervated by fibers deriving from the contralateral superior cervical ganglion. Studies in the previous funding period provide evidence that orbital connective tissue structures through which sympathetic nerves travel to their targets undergo a maturational change in their ability to support sympathetic ingrowth, the diminution in sympathetic ingrowth correlates temporally with the loss of the ability to establish contralateral innervation. Preliminary studies indicate that the connective tissue pathway is composed of a modified fibroblast, the myofibroblast, that has phenotypic characteristics intermediate between fibroblasts and smooth muscle, and can under some circumstances transdiffereritlate into smooth muscle cells. We hypothesize that certain types of myofibroblasts with phenotypic features closely aligned to those of smooth muscle may serve as intermediate targets for ingrowing sympathetic fibers and that during maturation, these myofibroblasts assume an altered phenotype which Is lese conducive to sympathetic sprouting. The objectives of the present study are to define the myofibroblast phenotype associated with sympathetic ingrowth, to determine the relationships between sympathetic nerves and myofibroblasts, and to determine whether a phenotypic shift represents a primary factor in diminished target reinnervation in the mature rat. In the first specific aim, we will characterize the structural and molecular phenotypes of orbital myofibroblasts during development using immunocytochemistry, in situ hybridization and electron microscopy. In aim 2 we will determine if the sympathetic ingrowth that occurs during visceral organ development and wound healing is associated with myofibroblasts of similar molecular and structural phenotype. In the third aim we will determine if the sympathetic fibers form neuroeffector contacts with the myofibroblasts using electron microscopy, retrograde tracer uptake, measurement of tissue contraction, and mympathetic denervation. In the fourth aim we will determine if the diminished ingrowth in the mature rat can be overcome by increasing the number of available neurons in close proximity to the orbit using intracranial sympathetic neuron transplant techniques. This study will provide basic information on the mechanisms of peripheral nerve pathway formation and the role of sympathetic innervation in wound healing, and may lead to therapeutic strategies aimed at facilitating reinnervation following degenerative disease, traumatic injury, and ban transplantation.
Keywords: developmental neurobiology, neural plasticity, neurogenesis, sympathetic nervous system, age difference, denervation, fibroblast, innervation, nervous system regeneration, nervous system transplantation, neuromuscular junction, neuronal guidance, smooth muscle, electron microscopy, immunocytochemistry, in situ hybridization, laboratory rat, neuronal transport, newborn animal
Project start date: 1987-06-01
Project end date: 1999-11-30
5R01NS023502-12 (1998): $221910
5R01NS023502-11 (1997): $214124
Sponsored Links Excellgen http://Excellgen.com
3R01NS023502-12S1 (1999): $25000
Female Pelvic Pain, Hormones,and Neuroplasticity
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01HD049615-02 from National Institute Of Child Health And Human Development IRG: UKGD
Abstract: Hormonal status and vaginal function are closely linked. Diminished reproductive hormones at menopause lead to vaginal atrophy and dryness. Menopause is often accompanied by dysesthetic vulvodynia, a pain syndrome consisting of burning and itching. Together with vulvar vestibulitis, an allodynia-like syndrome linked to early oral contraceptive use, vulvodynia represents an under-recognized but significant health problem, afflicting some 16% of the adult US female population. The etiology of these syndromes is poorly understood, although vulvar vestibulitis is associated with increased numbers of pain-sensing fibers. No animal models have been available to provide a better framework of understanding. Recently, we showed that estrogen regulates vaginal innervation in rats. Ovariectomy, which approximates human menopause, dramatically increases numbers of vaginal sensory nociceptors, as well as sympathetic and parasympathetic axons. We hypothesize that this is due to modulation of trophic factor release from vaginal tissues, and that altered innervation will influence key aspects of vaginal function, including blood flow, vascular permeability, and pain sensitivity. In aim 1 we propose to characterize the relationship between hormonal status and vaginal innervation in rats during the estrous cycle, pregnancy, and adult and juvenile hormone administration. We also determine if human vaginal innervation varies with hormonal state. Aim 2 assesses cellular mechanisms underlying axonal remodeling by determining effects of reproductive hormones on vaginal target tissue and on sensory and autonomic neurons. Aim 3 examines molecular mechanisms mediating vaginal remodeling by investigating expression and functional relevance of potential trophic factors. In aim 4, we assess the functional significance of vaginal nerve remodeling on blood flow, neurogenic inflammation and behavioral avoidance of painful stimuli. These studies are conducted using methods in cell biology, tissue culture, molecular biology, physiology, pharmacology and behavior. The findings of these experiments will provide insight into mechanisms underlying hormone-dependent remodeling of vaginal innervation, and whether altered innervation may contribute to vaginal dysfunction. Moreover, these studies will provide a better understanding of the relationship between vaginal nerve plasticity and vulvodynia, and potentially lead to new therapeutics aimed at reversing vaginal sensory hyperinnervation.
Keywords: female, hormone, innervation, neural plasticity, pain, tissue, atrophy, axon, behavior, biopsy, blood, burn, calcitonin gene related peptide, cell biology, conditioning, culture, dendrite, density, estrogen, estrogen receptor, estrus, gene, gene expression, growth media, health, health /scientific organization, human, inflammation, insight, juvenile hormone, lead, menopause, microarray technology, model, molecular biology, nerve, neuron, neuropeptide, nociceptor, oral contraceptive, ovariectomy, pharmacology, physiology, pregnancy, protein, pruritis, reproductive hormone, role, sectioning, soma, steroid, syndrome, tissue /cell culture, touch, vagina, wakefulness, clinical research
Project start date: 2006-04-16
Project end date: 2011-01-31
5R01HD049615-02 (2007): $266561
1R01HD049615-01A1 (2006): $274523
Kansas Mental Retardation And Developmental Disabilities Research Center (MRDDRC)
Peter G Smith
Bureau Of Child Researchuniversity Of Kansas Lawrence
2385 Irving Hill Road
lawrence, Ks 660457563
Grant 5P30HD002528-42 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development IRG: ZHD1
Abstract: Core Support for five years is requested for the competitive renewal of the Kansas Mental Retardation and Developmental Disabilities Research Center (MRDDRC). The Kansas MRDDRC, now in its 39th year, has played a major international role in generating highly effective behavioral interventions aimed at the causes, prevention, and treatment of mental retardation and related secondary conditions, and in delineating basic knowledge of the underlying biology of typical and atypical development. Since its inception, the center has supported a balanced portfolio of behavioral and biological research. Building on this rich history, a unique contribution of the center in the future will be the development of biologically informed behavioral and pharmacological intervention and treatment approaches. The mission of the Kansas MRDDRC is to support high quality basic and applied research relevant to the causes and prevention of mental retardation and the prevention and remediation of associated secondary conditions and related developmental disabilities. To achieve this mission, the Kansas MRDDRC is designed to accomplish three objectives. First, to develop and support new interdisciplinary basic and applied research initiatives directly relevant to the center´s mission, bringing together scientists across the Kansas Center as well as promoting collaborative ventures with researchers at other institutions. Second, to provide cost-effective, scientifically generative, state of the art core services, resources, and facilities that directly enhance the quality and impact of science produced by center investigators and their collaborators. Third, to provide highly efficient, cost-effective systems for planning, developing, managing, coordinating, and disseminating research activities associated with the center. The Kansas MRDDRC´s research program is organized around four integrated thematic areas that each reflects a general topic central to MRDD as well as the scientific directions and strengths of our current efforts. These themes are 1) language, communication, and cognition of mental retardation; 2) risk, prevention, and intervention in mental retardation; 3) neurobiology of mental retardation; 4) cellular and molecular biology of early development. To coordinate and support the research activities of the 76 investigators and 75 research projects associated with these themes, four core units are proposed a) Communication and Administration; b) Biobehavioral Measurement; c) Research Design and Analysis; d) Integrative Imaging
Keywords: behavior modification, biomedical facility, developmental disease /disorder, health science research, mental retardation clinical research
Project start date: 1991-08-01
Project end date: 2011-06-30
5P30HD002528-42 (2008): $1486729
NGF AND POST-INFARCT SYMPATHETIC NEUROPLASTICITY
Peter G Smith, Director
University Of Kansas Medical Center, Msn 1039, Kansas City, Ks 66160
Grant 5R01HL079652-05 from National Heart, Lung, And Blood Institute
Abstract: Arrhythmias and cardiac dysfunction occur when sympathetic neural influences are excessive. Recent evidence indicates that structural remodeling of cardiac nerves contributes to hyperexcitability. Because nerve growth factor (NGF) is the major protein regulating sympathetic innervation, it is implicated in sympathetic neuroplasticity. In the present application we test the hypothesis that abnormal NGF synthesis after myocardial infarction leads to cardiac sympathetic nerve remodeling. We propose that abnormally high NGF expression in peri-infarct inflammatory myofibroblasts and macrophages contributes to hyperinnervation, and that deficient NGF expression in parasympathetic neurons leads to loss of parasympathetic presynaptic inhibition of sympathetic nerves. The long-term goals of this study are to understand the molecular mechanisms that regulate cardiac sympathetic innervation and to devise interventional strategies to correct abnormal innervation patterns. Experiments in Aim 1 demonstrate that coronary artery ligation in rats upregulates NGF in specific subsets of inflammatory cells. Aim 2 explores temporo-spatial features of ingrowth of identified axons and assesses the role of trophic factors in this process. Aim 3 investigates if sympathetic innervation itself promotes inflammatory cell NGF expression via beta adrenergic receptors. In Aim 4 we assess whether NGF expression in cardiac parasympathetic neurons, which may govern formation of axo-axonal inhibitory synapses, is regulated by sympathetic innervation. In Aim 5 we examine the role of adrenergic receptors in regulating cardiac parasympathetic NGF synthesis. Aim 6 investigates the possibility that adrenergic receptor down-regulation leads to diminished cardiac parasympathetic NGF synthesis in heart failure. Aim 7 investigates whether reduced parasympathetic NGF can account for diminished axo-axonal inhibition in heart failure. We use morphometric histochemistry, cell and tissue culture, protein and mRNA assays, and in vivo recordings to attain these goals. These studies will provide new and important information on molecular mechanisms regulating sympathetic neuroplasticity within the damaged heart, thus providing a more complete understanding of post-infarct cardiac dysfunction. Importantly, they will provide novel data on how trophic factor synthesis is regulated by adrenergic receptors, and may serve as a basis for pharmacological interventions aimed at preventing or reversing deleterious cardiac sympathetic remodeling
Keywords: Accounting; Adrenergic Agonists; Adrenergic Receptor; Adrenergic Receptor Agonist; Adrenoceptors; Adrenomimetics; Antibodies, Blocking; Arrhythmia; Assay; Axon; Bioassay; Biologic Assays; Biological Assay; Blocking Antibodies; Body Tissues; CNS plasticity; Cardiac; Cardiac Arrhythmia; Cardiac Failure Congestive; Cardiac artery; Cardiac infarction; Cell/Tissue, Histochemistry; Cells; Chemical Sympathectomy; Chemosympathectomy; Classification; Closure by Ligation; Co-culture; Cocultivation; Coculture; Coculture Techniques; Common Rat Strains; Congestive Heart Failure; Coronary artery; Data; Death, Sudden; Denervation, Sympathetic, Chemical; Down-Regulation, Receptor; Dysfunction; ELISA; Enzyme-Linked Immunosorbent Assay; Family; Functional disorder; Ganglia; Ganglia, Parasympathetic; Ganglion Cysts; Ganglionic Cysts; Ganglions; Genetics, in situ Hybridization; Goals; Heart; Heart Arrhythmias; Heart Decompensation; Heart Failure, Congestive; Heart artery; Heart failure; Histochemistry Cell/Tissue; Immune; Immunofluorescence; Immunofluorescence Immunologic; Immunologic, Immunofluorescence; In Situ Hybridization; In Vitro; Individual; Infarction; Inflammatory; Inhibitory Synapse; Injury; Intermediary Metabolism; Intervention; Intervention Strategies; Investigators; Lead; Left Coronary Artery; Left coronary artery structure; Ligation; METBL; Mammals, Rats; Mediating; Messenger RNA; Metabolic Processes; Metabolism; Modification; Molecular; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Myocardial; Myocardial Infarct; Myocardial Infarction; Myofibroblast; Myxoid cyst; Nerve; Nerve Cells; Nerve Growth Factors; Nerve Unit; Nervous; Neural Cell; Neural Ganglion; Neurocyte; Neuronal Plasticity; Neuronotrophic Factors; Neurons; Neurotrophic Factors; Neurotrophic Proteins; Neurotrophins; Pattern; Pb element; Peripheral; Phase; Physiologic; Physiological; Physiopathology; Process; Production; Programs (PT); Programs [Publication Type]; Proliferating; Proteins; RNA, Messenger; RT-PCR; RTPCR; Rat; Rattus; Receptor Down-Regulation; Receptors, Epinephrine; Research Personnel; Researchers; Reverse Transcriptase Polymerase Chain Reaction; Rodent Model; Role; Site; Structure of parasympathetic ganglion; Sudden Death; Sympathectomy; Sympathectomy, Chemical; Sympathetic Denervation; Sympathetic Ganglia; Synapses; Synaptic; Systematics; Testing; Therapeutic; Tissues; adenoreceptor; base; beta-adrenergic receptor; cardiac failure; cardiac infarct; cardiac innervation; cell type; coronary attack; coronary infarct; coronary infarction; experiment; experimental research; experimental study; gene product; heart attack; heart infarct; heart infarction; heart innervation; heavy metal Pb; heavy metal lead; in situ Hybridization Staining Method; in vivo; infarct; innervation; interventional strategy; left coronary artery; mRNA; macrophage; member; nerve supply; neural; neural plasticity; neuronal; neuroplasticity; neurotrophic factor; neurotrophin; neutrophin; novel; pathophysiology; presynaptic; prevent; preventing; programs; protein expression; relating to nervous system; research study; response; reverse transcriptase PCR; social role; tissue culture
Project start date: 2005-04-01
Project end date: 2011-03-31
Budget start date: 1-APR-2009
Budget end date: 31-MAR-2011
5R01HL079652-05 (2009): $278765
5R01HL079652-03 (2007): $278765
5R01HL079652-02 (2006): $287091
1R01HL079652-01A2 (2005): $294000
NEUROTROPHINS, HORMONES AND POSTPAROUS INCONTINENCE
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01HD038670-05 from National Institute Of Child Health And Human Development IRG: ZHD1
Abstract: Adapted from Applicant s Description) Traumatic labor and vaginal delivery during childbirth can produce permanent dysfunction of the pelvic musculature, in many cases leading to urinary and fecal incontinence. Damage to the pelvic nerves and failure to achieve complete reinnervation account for much of the deficit. Factors that modulate regrowth of damaged axons therefore may influence functional recovery. The investigators have shown recently that smooth muscle of the reproductive tract, which shares many similarities with urethral and anal sphincter smooth muscle, undergoes dramatic changes in innervation as a consequence of hormonal fluctuations. Elevated plasma estrogen results in marked reductions in numbers of sympathetic nerves, while other neuronal populations are unaffected. Preliminary data suggest that these changes are related to decreased nerve growth factor (NGF) synthesis. The investigators hypothesize that the high levels of estrogen in periparous females result in depressed neurotrophin synthesis in pelvic smooth muscle. Accordingly, sympathetic nerves, whose presence is essential for normal sphincter contractile tone, fail to regenerate to their full potential after nerve injury. In Specific Aim 1, the investigators will determine the effects of estrogen and pregnancy on protein and mRNA levels of NGF and the related neurotrophin, NT3, in urethral and anal sphincter smooth muscle using in situ hybridization, quantitative competitive polymerase chain reaction, immunohistochemistry and enzyme-linked immunoassays. In the second aim, they will use quantitative in situ hybridization and immunohistochemistry to determine the extent to which estrogen and pregnancy influence expression of the neurotrophin receptors trkA and p75NTR, which mediate the sympathetic nerve response to NGF and NT3. In aim 3, they will use immunohistochemistry to examine the effects of estrogen and pregnancy on the normal innervation of the urethral and anal sphincter smooth muscles. Aim 4 will employ immunohistochemistry and physiological and pharmacological measurements of urethral and anal smooth muscle contractile function to assess the effects of estrogen on sphincter reinnervation following a noradrenergic neurotoxin lesion with 6-hydroxydopamine, or pelvic distension to simulate childbirth trauma, and these will be compared with injury of normal delivery. The fifth aim uses collagen gel co-cultures of sphincter smooth muscle and sympathetic ganglia in the presence of selective neutralizing antibodies to ascertain the roles of neurotrophins in modulating sympathetic neurite sprouting toward smooth muscle of estrogen-treated or pregnant rats. These studies should provide important new information on how hormones may affect neurotrophin synthesis by smooth muscle of the organs of continence, and how this in turn may alter sympathetic reinnervation of sphincters after axonal damage due to traumatic vaginal delivery, thus leading to urinary and fecal incontinence.
Keywords: birth, fecal incontinence, hormone regulation /control mechanism, neurotrophic factor, pathologic process, urinary incontinence, estrogen, innervation, messenger RNA, nerve growth factor, neuronal guidance, pregnancy, receptor expression, rectum /anus, smooth muscle, urinary tract, female, immunocytochemistry, in situ hybridization, laboratory rat, neutralizing antibody, polymerase chain reaction, tissue /cell culture, women s health
Project start date: 2000-04-01
Project end date: 2006-03-31
5R01HD038670-05 (2004): $225254
5R01HD038670-04 (2003): $218693
Sponsored Links Excellgen http://Excellgen.com
5R01HD038670-02 (2001): $206139
1R01HD038670-01 (2000): $200135
Peter G Smith
University Of Kansas Medical Center
Project start date: 2011-04-01
Project end date: 2013-03-31
FEMALE PELVIC PAIN, HORMONES,AND NEUROPLASTICITY
Peter G Smith, Director
University Of Kansas Medical Center, Msn 1039, Kansas City, Ks 66160
Grant 5R01HD049615-05 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Keywords: 21+ years old; Adolescent; Adolescent Youth; Adult; Animal Model; Animal Models and Related Studies; Atrophic; Atrophy; Autonomic ganglion; Axon; Behavior; Behavioral; Biological; Biopsy; Blood flow; Body Tissues; Burn injury; Burning Pain; Burning vulva; Burns; CGRP; CNS plasticity; Calcitonin Gene-Related Peptide; Caliber; Causality; Cell Body; Cellular biology; Change of Life, Female; Chemotherapy-Hormones/Steroids; Common Rat Strains; Contraceptive Usage; Contraceptives, Oral; Culture Media; DNA Molecular Biology; Diameter; Discomfort of Vulva; Disease; Disorder; Down-Regulation; Down-Regulation (Physiology); Downregulation; Dryness; Dysfunction; Endocrine Gland Secretion; Estrogen Receptors; Estrogenic Agents; Estrogenic Compounds; Estrogens; Estrous Cycle; Estrus; Etiology; External Genitalia; Female; Fiber; Functional disorder; Gene Expression; Gene Proteins; Genital; Genital System, Female, Vagina; Genital system; Gestation; Gonadal Steroid Hormones; Health; Hormonal; Hormones; Human; Human, Adult; Human, General; Immunoblotting; In Vitro; Insect Growth Regulators; Intervention; Intervention Strategies; Itching; Juvenile Hormones; Lead; Link; Mammals, Rats; Man (Taxonomy); Man, Modern; Mediating; Menopausal Syndrome; Menopause; Menopause Syndrome; Methods; Microarray Analysis; Microarray-Based Analysis; Molecular; Molecular Biology; Nerve; Nerve Cells; Nerve Unit; Nervous; Neural Cell; Neurites; Neurocyte; Neurogenic Inflammation; Neuronal Plasticity; Neurons; Neuropeptides; Nociceptors; Oophorectomy; Operation; Operative Procedures; Operative Surgical Procedures; Oral Contraceptives; Ovariectomy; Pain; Painful; Pains, Burning; Pb element; Pelvic Pain; Peripheral Nerves; Pharmacology; Physiology; Physiopathology; Population; Pregnancy; Protein Gene Products; Proteins; Pruritic Disorder; Pruritis; Pruritus; RT-PCR; RTPCR; Rat; Rattus; Response Latencies; Reverse Transcriptase Polymerase Chain Reaction; Role; Sensory; Sex Hormones; Sex Steroid Hormones; Stimulus; Surgical; Surgical Interventions; Surgical Procedure; Syndrome; Testing; Therapeutic Estrogen; Therapeutic Hormone; Tissues; Touch; Touch sensation; Vagina; Vaginal; Vascular Permeabilities; Vulva; Vulval discomfort; Vulvar discomfort; Vulvodynia; adult human (21+); allodynia; awake; behavior test; behavioral test; birth control pill; cell biology; cell body (neuron); contraceptive use; density; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; estrous; experiment; experimental research; experimental study; female gonadectomy; gene product; gonadal steroids; growth media; heavy metal Pb; heavy metal lead; innervation; insight; interventional strategy; juvenile; juvenile human; menopausal; microarray technology; model organism; nerve supply; neural cell body; neural mechanism; neural plasticity; neuromechanism; neuronal; neuronal cell body; neuroplasticity; new therapeutics; next generation therapeutics; novel therapeutics; pathophysiology; protein expression; release factor; reproductive; reproductive hormone; research study; reverse transcriptase PCR; sex steroid; social role; soma; surgery; tissue culture; urogenital system (genital part); vulvar vestibulitis
Project start date: 2006-04-16
Project end date: 2011-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
5R01HD049615-05 (2010): $258617
CONVERSION OF PARASYMPATHETIC FUNCTION AFTER INJURY
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01HD033025-03 from National Institute Of Child Health And Human Development IRG: NLS
Project start date: 1994-09-01
Project end date: 1999-08-31
5R01HD033025-03 (1996): $165894
Peter G Smith
University Of Kansas Medical Center Msn 1039 Kansas City, Ks 66160
Grant 5R01NS023502-10 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Project start date: 1987-06-01
Project end date: 1998-11-30
5R01NS023502-10 (1996): $202241