Research Interests: The Autonomic and Sensory Neurobiology Lab studies the central nervous system (CNS) and peripheral nervous system (PNS) autonomic and sensory circuits associated with the female reproductive system. Primary sensory neurons link the reproductive organs with the spinal cord . The spinal cord circuits include autonomic outputs as well as ascending influences to brainstem and hypothalamus. There are hypothalamic and brainstem circuits back to spinal cord and autonomic outflow. Many of these circuits contain estrogen receptors and could be influenced by circulating steroids. In addition, primary sensory neurons likely influence uterine cervical ripening at parturition. We use immunohistochemistry, tract tracing, in situ hybridization and molecular techniques to analyze the neurotransmitter and receptor components of these circuits.

We thank the National Institutes of Neurological Disorders and Stroke of the NIH for supporting this work.

Laboratory Personnel:

Director:	Raymond E. Papka, Ph.D., Professor
Technical support:	Sharon Usip, B.S., M.S. Cell and molecular biology studies.
	Jen Hafemeister, B.S. Cell and molecular biology studies.
	Megan Storey-Workley, B.S., M.S. Medical Neuroscience course support, immunohistochemical studies, tract-tracing, stereotaxic surgery.
Future personnel:	If you are interested in the work of the Autonomic and Sensory Neurobiology Laboratory and would like to join us, contact Raymond E. Papka at 330-325-6636 or email rpapka@neoucom.edu.

Projects:

Female Reproductive Organs and Their Innervation
Principal Investigator: Raymond E. Papka
Funding source: National Institutes of Neurological Disorders and Stroke

1.	Studies on neurobiology of autonomic and primary sensory neurons as they influence the functioning of the female reproductive system during pregnancy and parturition.
2.	Studies on the neurochemicals released from autonomic and sensory neurons that influence cervical ripening and parturition.
3.	Studies on sensory neurons and neurogenic inflammation (neuroimmunology) and involvement of these factors in uterine cervical ripening at parturition.
4.	Estrogen receptor gene expression (estrogen receptor alpha and beta) in neurochemically identified and organ-identified primary sensory, autonomic and spinal cord neurons.
5.	Expression of NK1 receptors for substance P and calcitonin gene-related peptide (CGRP) receptors in sensory circuits and target organs during pregnancy.
6.	Plasticity in sensory and autonomic neurons during pregnancy - including expression of glutamate in peripheral sensory neurons at sites of inflammation.

Neurochemical Spinal Circuitry and Uterine Innvervation
Principal Investigator: Raymond E. Papka
Funding source: National Institutes of Neurological Disorders and Stroke

1.	Studies on neurochemical circuits involving the PNS and CNS neurons and connections that influence the reproductive organs.
2.	Studies on neuroanatomical and neurochemical circuitry for visceral sensory and nociceptive processing in the spinal cord as it relates to analgesia (?) at parturition.
3.	Axonal tracing strategies for identification of organ specific neurons in the PNS & CNS.
4.	Changes in estrogen, estrogen receptors and neurotransmitter expression in sensory & autonomic neurons and spinal cord neurons during pregnancy.
5.	CNS hypothalamo-spinal circuits that utilize oxytocin and/or corticotrophin releasing hormone (CRH) and impinge on the lumbosacral spinal cord.
6.	Oxytocin and CRH receptors in the spinal cord.
7.	NK1 and CGRP receptors in the spinal cord during pregnancy.

Recent Laboratory Publications:

Papka, R.E. and D.L. McNeill (1992) Coexistence of calcitonin gene-related peptide- and galanin-immunoreactivity in female rat pelvic and dorsal root ganglia. Peptides, 13:761-767.

Shew, R.L., R.E. Papka and D.L. McNeill (1992) Galanin- and calcitonin gene-related peptide immunoreactivity in nerves of the rat uterus: Localization, co-localization and effects on uterine contractility. Peptides, 13:273-279.

McNeill, D.L., R.L. Shew, J.M. Holzbeirlein and R.E. Papka (1992) Effects of spinal cord transection and MK-801 on CGRP immunostaining in the rat urinary bladder. Exp. Neurol., 116:339-344.

Papka, R.E. and D.L. McNeill (1992) Is there a synaptic innervation of pelvic neurons by calcitonin gene-related peptide-immunoreactive sensory nerves? Annals New York Acad. Sci., 657:477-480.

McNeill, D.L., C.H. Harris, J.M. Holzerbeierlein, R.L. Shew, N.E. Traugh and R.E. Papka (1992) CGRP-immunoreactive primary afferent nerve fibers in the rat urinary bladder: Effects of dorsal rhizotomy and MK-801. Exp. Neurol.,118:317-323.

McNeill, D.L., R.E. Papka and C.H. Harris (1992) CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis. Peptides, 13:1239-1246.

McNeill, D.L., N.E. Traugh, A.M. Vaidya, H.T. Hua and R.E. Papka (1992) Origin and distribution of NADPH-diaphorase-positive neurons and fibers innervating the urinary bladder of the rat. Neurosci. Lett., 147:33-36.

Papka, R. E. and D.L. McNeill (1992) Distribution of NADPH-diaphorase- positive nerves in the uterine cervix and neurons in dorsal root and paracervical ganglia of the female rat. Neurosci. Lett., 147:224-228.

Traurig, H.H. and R.E. Papka (1993) Autonomic and Visceral Sensory Innervation of the Female Reproductive System: Special Reference to the Functional Roles of Nerves in Reproductive Organs. IN: The Autonomic Nervous System, series ed. G. Burnstock; Vol VI:Nervous Control of the Urogenital System, ed. by C.A. Maggi. Harwood Academic Publishers, pp. 104-141.

Papka, R.E. and H.H. Traurig (1993) Autonomic and Visceral Sensory Innervation of the Female Reproductive System: Special Reference to Neurochemical Markers in Nerves and Ganglionic Connections. IN: The Autonomic Nervous System, series ed. G. Burnstock; Vol VI:Nervous Control of the Urogenital System, ed. by C.A. Maggi. Harwood Academic Publishers. pp 421-464.

Papka, R.E. and D.L. McNeill (1993) Light and electron microscopic study of synaptic connections in the paracervical ganglia of the female rat: Special reference to calcitonin gene-related peptide-, galanin- and tachykinin (substance P and neurokinin A)-immunoreactive nerve fibers and terminals. Cell and Tissue Research, 271:417-428.

Shew, R.L., R.E. Papka, D.L. McNeill and J.A. Yee (1993) NADPH- diaphorase-positive nerves and the role of nitric oxide in CGRP relaxation of uterine contraction. Peptides, 14:637-641.

Papka, R.E. and R.L. Shew (1994) Neural input to the uterus and influence on uterine contractility. Invited review chapter. In: CONTROL OF UTERINE CONTRACTILITY, Garfield, R.E. and Tabb T. editors. CRC Press. pp. 376-399.

Sullivan, K.A., H.H. Traurig and R.E. Papka (1994) Ontogeny of neurotransmitter systems in the paracervical ganglion and uterine cervix of the rat. Anat. Rec., 240:377-386.

Hamilton, M.O., R.E. Papka, D.L. O'Donoghue, A.M. Vaidya, S.J. Williams, C.R.D. Poff and D.L. McNeill (1995) Spinal projection neurons to the pontine micturition center: Relationship to preganglionic neurons and nitric oxide synthase. J. Comp. Neurol. , 353:1-8.

Papka, R.E., D.L. McNeill, D. Thompson and H.H.W. Schmidt (1995) Nitric oxide nerves in the uterus are parasympathetic, sensory and contain neuropeptides. Cell Tiss. Res. 279:339-349.

Papka, R.E., J. R. McCurdy, S. J. Williams, B. Mayer, L. Marson and K.B. Platt (1995) Parasympathetic preganglionic neurons in the spinal cord involved in uterine innervation are cholinergic and nitric oxide-containing. Anatomical Record, 241:554-562.

Papka, R.E., B.D. Thompson and H.H.H.W. Schmidt (1996) Identification of uterine-related sympathetic neurons in the rat inferior mesenteric ganglion: Neurotransmitter content and afferent input. J. Autonom. Nerv. Syst. 59:51-59.

Williams, S.J. and R.E. Papka (1996) Estrogen receptor-immunoreactive neurons are present in the female rat lumbar spinal cord. J. Neurosci. Res. 46:492-501.

Papka, R.E., B. Srinivasan, K. E. Miller, and S. Hayashi (1997) Localization of estrogen receptor protein and estrogen receptor mRNA in peripheral autonomic and sensory neurons. Neuroscience 79:1153-1163.

Williams, S.J., K.Chung, A.S. OM and R.E. Papka (1997) Estrogen receptor concentrations in the lumbosacral spinal cord flucuate during the estrous cycle. Life Sciences 61(26):2551-2559.

Papka, R.E., S.J. Williams, K.E. Miller, T.M. Copelin, and P. Puri (1998) CNS Location of uterine-related neurons revealed by transsynaptic tracing with pseudorabies virus and their relationship with estrogen-receptor-immunoreactive neurons. Neuroscience 84:935-952.

Williams, S.J. and R.E. Papka (1998) Differential numbers of estrogen receptor-immunoreactive neurons in the lumbosacral spinal cords of intact, ovariectomized and pregnant rats. (submitted to Neuroscience, 11-20-97, in revision).

Williams S.J. and R.E. Papka (1998) Influence of progesterone and tamoxifen on estrogen receptors in spinal cord neurons. (Submitted to Brain Research Bulletin, 11-26-97, in revision).

Collins J.J., C.E. Lin, H.R. Berthoud, and R.E. Papka (1999) Vagal afferents from the uterus and cervix provide direct connections to the brainstem. Cell Tissue Res., 295:43-54.

Papka, R.E., H.H. Traurig, M. Schemann, J. Collins, T. Copelin and K. Wilson (1999) Cholinergic neurons of the pelvic autonomic ganglia and uterus of the female rat. Distribution of axons and presence of muscarinic receptors. Cell Tiss Res, 296:293-305.

Papka, R.E., J. Collins, T. Copelin and K. Wilson (1999) Calretin-immunoreactive nerves in the uterus, pelvic autonomic ganglia, lumbosacral dorsal root ganglia and lumbosacral spinal cord. Cell Tissue Research, 298:63-74.

Collins, J.J., K. Wilson, R. Fischer-Colbrie and R.E. Papka (2000) Distribution and origin of secretoneurin-immunoreactive nerves in the female rat uterus. Neuroscience, 95:255-264.

Puder, B.A. and R.E. Papka (2001) Hypothalamic paraventricular axons projecting to the female rat lumbosacral spinal cord contain oxytocin. J. Neurosci. Res., 64:53-60.

R. E. Papka, M. Storey-Workley, P.J. Shughrue , I. Merchenthaler , J.J. Collins, S. Usip, P.T.K. Saunders, and M. Shupnik (2001) Estrogen receptor-a and -b-immunoreactivity and mRNA in neurons of sensory and autonomic ganglia and spinal cord. Cell and Tissue Research 304:193-214.

Puder, B.A. and R.E. Papka (2001) Distribution and origin of corticotropin releasing factor immunoreactive axons in the female rat lumbosacral spinal cord. (J Neurosci Res, 66:1217-1225).

Collins J.J., S. Usip, K.E. McCarson and R.E. Papka (2002) Sensory Nerves and Neuropeptides in Uterine Cervical Ripening. Peptides 23:167-183.

Papka, R.E. and M. Storey-Workley (2002) Estrogen Receptor-a and -b Coexist in a Subpopulation of Sensory Neurons of Female Rat Dorsal Root Ganglia. Neuroscience Letters 319:71-74.

Pokabla, M.J., I.M. Dickerson, and R.E. Papka (2002) Calcitonin gene-related peptide-receptor component protein (CGRP-RCP) immunoreactivity in the cervix, lumbosacral dorsal root ganglia, and lumbosacral spinal cord. Peptides 23:507-514.

Papka, R.E., J. Hafemeister, B.A. Puder, S. Usip, and M. Storey-Workley (2002) Estrogen receptor-a and neural circuits to the spinal cord during pregnancy. J. Neurosci. Res. 70:808-816.

Mowa, CN, J. Collins, S. Usip, M. Storey-Workley, R. Amann, and R. E.Papka (2003) Substance P in the uterine cervix, dorsal root ganglia and spinal cord during pregnancy and the effect of estrogen on SP synthesis. Peptides (in press).

PAPKA, R.E. and C.N. Mowa (2003). Invited review. Estrogen receptors in the spinal cord, sensory ganglia and pelvic autonomic ganglia. A review. International Review of Cytology: A Survey of Cell Biology, ed. By K.W. Jeon, vol 231: 91-127.

MOWA,CN, S Usip, J Collins, M Storey-Workley, KM Hargreaves and RE Papka (2003) The effects of pregnancy and estrogen on the expression of Calcitonin Gene-Related Peptide (CGRP) in the uterine cervix, dorsal root ganglia and spinal cord . Peptides 24:1163-1174.

Berkley , Karen J, Natalia Dmitrieva, Kathleen S. Curtis, Raymond E. Papka (2004) Innervation of Ectopic Endometrium in a Rat Model of Endometriosis . Proc. Natl Acad Sci (PNAS), 101:11094-11098.

Mowa , CN and RE Papka (2004) Neuropeptides and uterine cervical ripening. Invited review for J. Histochemistry and Cytochemistry, 52:1249-1258.

Papka , R.E., M. Storey-Workley, J. Hafemeister (2005) P2X receptors in the rat uterine cervix, dorsal root ganglia and spinal cord during pregnancy. Cell and Tissue Research, 321(1):35-44.

Berkley K, Rapkin A, and RE Papka (2005) The Pains of Endometriosis Science 308:1587-1589.

Papka RE, M Storey-Workley, S. Usip, CN Mowa, J Fahrenkrug, (2005) Expression of pituitary adenylate cyclase activating peptide in the uterine cervix, lumbosacral dorsal root ganglia and spinal cord of rats during pregnancy. Peptides (in press 8-12-05).

Puder , B.A. and R. E. Papka (2005) Activation and Circuitry of Uterine-Cervical-Related Neurons in the Lumbosacral Dorsal Root Ganglia and Spinal Cord at Parturition. J. Neurosci. Res. (in press).

Collaborations:

The following groups are kindly helping to fill gaps in our techniques, provide stimulation and much needed data. They are much needed and appreciated connections.

Jan Fahrenkrug, M.D. - Univ. Copenhagen, Denmark - Pituitary adenylate cylcase activity peptide (PACAP) studies.

Rainer Amann - Univ. Graz, Austria - Substance P and nerve growth factor studies.

Ken Miller, Ph.D. - Univ. Oklahoma - Expression of glutamate in peripheral terminals of primary sensory neurons.

Reiner Fischer-Colbrie, Ph.D. - Univ. Innsbruck, Austria - Secretoneurin assays.

Ken Hargreaves, Ph.D., - Univ. Texas San Antonio - CGRP assays.

Ian Dickerson, Ph.D. - Univ. Miami - CGRP receptor gene expression. John Maggio, Ph.D. - Univ. Cincinnati - Substance P assays.

Ken McCarson, Ph.D. - Univ. Kansas - Substance P mRNA and NK1 receptor mRNA assays.

Paul Shughrue, Ph.D. and Istvan Merchenthaler, M.D., Ph.D. - Women's Health Research Inst., Wyeth-Ayerst Research - In situ hybridization.