Thesis (M.S.)--Missouri State University, 2008. / "August 2008." Includes bibliographical references (leaves 101-112). Also available online.

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Speech-Language Pathology, Department of Speech Pathology and Audiology. Title from pdf file main screen (viewed on July 25, 2010). Includes bibliographical references.

Quinze cabeças de tubarões Carcharias taurus (Rafinesque, 1810), pertencentes à Ordem Lamniformes e Família Odontaspididae, foram utilizadas para a realização desse estudo. O material destinado à análise foi obtido junto ao Terminal de Pesca de Santos, localizado em Santos, São Paulo, e descartado pelos pescadores por não apresentar valor comercial. A dissecação das cabeças visou caracterizar os músculos mandibulares, bem como descrever sua inervação realizada pelo ramo mandibular do nervo trigêmeo. Os músculos mandibulares de C. taurus são representados por: músculo pré-orbital, músculo levantador do palatoquadrado, músculo quadrado-mandibular e músculo intermandibular. O nervo trigêmeo de C. taurus origina-se em uma porção lateral da medula oblonga e ramifica-se na órbita para originar o ramo mandibular responsável pela inervação dos músculos derivados do arco mandibular. Os ramos proximais do ramo mandibular do nervo trigêmeo inervam o músculo levantador do palatoquadrado, o músculo pré-orbital e o músculo quadrado-mandibular recebem fibras dos ramos intermediários do ramo mandibular do nervo trigêmeo e a ramificação distal do mesmo é visualizada no músculo intermandibular. / During this study were used fifteen of Carcharias taurus (Rafinesque, 1810) (Odontaspididae, Lamniformes, Elasmobranchii) shark heads. The analised material was obteined in Terminal de Pesca de Santos, located in Santos, São Paulo. The material was descarded by the fishers because it hasn´t none comercial value. The heads dissection is foccated in the caracterization of the mandibular muscles and to discrebed the mandibular branch of the trigeminal nerve innervation as well. The C. taurus mandibular muscles are represented by: muscle pré-orbital, muscle levantador do palatoquadrado, muscle quadrado-mandibular and muscle intermandibular. The origin of the trimeginal nerve of C. taurus is located in a lateral portion of the medula oblonga. In the orbita it ramificates to originate de mandibular branch that inervates the muscles which is derived from the mandibular arch. The mandibular branch of the trigeminal nerve\'s proximal branches inervetes the muscle levantador do palatoquadrado, the muscles pré-orbitall and quadrado-mandibular receives fibers from the intermediate branches of the mandibular branch of the trigeminal nerve and the distal ramification of the mandibular branch are visualised in the muscle intermandibularis.

Blocking the contents of the pterygopalatine fossa (PPF) is a highly effective method in alleviating pain in trigeminal neuralgia (TN) and other facial pain syndromes. This, however, is not a widely used technique, due to the difficulty in locating the PPF which is obscured by bony and soft tissue structures. Despite the various unspecific techniques that have been attempted, in many cases radiography still seems to be used as it is the most effective method in locating the PPF. The aim of this study was therefore to achieve a safe and alternative method of locating the PPF including its contents without the aid of radiography. A total of 160 skulls from the Pretoria Bone Collection at the University of Pretoria were used. Distinct anatomical landmarks and the use of existing and new anthropometric measurements were used to define the location of the PPF in any individual. Regression analysis provided the strength of influence each measurement had on the location of the PPF. From the results, two mathematical formulae were devised (one for each side). These formulae were tested on 47 cadavers by substituting the measurements of each individual into the created formulas. A needle was then inserted at the calculated points, and the area around the needle dissected to determine whether or not it was in the PPF. Our results showed an accuracy of 65.22% on the right and 54.35% on the left. It is hoped that this new technique will aid researchers and clinicians alike in the management of various pain disorders as well as pain management during surgery. AFRIKAANS : Daar is bevind dat ‘n lokale verdowingsblok van die inhoud van die pterygopalatine fossa (PPF) die pyn effektief verlig vir trigeminale senuweepyn, sowel as ander pyn sindrome. Die tegniek word egter nie gereeld gebruik nie as gevolg daarvan dat dit moeilik is om die PPF te betree deurdat dit deur verskeie benige en sagte weefsels verberg word. Die literatuur beskryf verskeie onspesifieke metodes om die prosedure uit te voer, maar in die meeste gevalle moes radiografie gebruik word om sukses te behaal. Die doel van hierdie projek was om ’n alternatiewe metode te ontwikkel wat veilige en effektiewe toegang tot die PPF bied, sonder om radiografie te gebruik. ’n Totaal van 160 skedels was gebruik om anatomies landmerke en bestaande sowel as nuwe antropologiese metings te maak. Regresie analise het die sterkte van die invloed van die onderskeie metings met die pterygopalatine fossa gemeet. Vanuit die resultate van die statistiese analise is twee formules ontwerp (een vir elke kant van die gesig). Die formules was getoets op 47 kadavers deur die metings vir elke individu in die formules te plaas. ‘n Naald is dan geplaas in die uitgewerkte punt, die area om die naald was gedisekteer om te sien of die naald in die fossa en dus by die ganglion was of nie. Die resultate toon ‘n akkuraatheid van 65.22% aan die regterkant en 54.35% aan die linkerkant. Daar word gehoop dat hierdie nuwe tegniek ‘n effektiewe manier van pyn behandeling word in verskeie pyn sindrome sowel as gedurende chirurgie vir beide navorsers en chirurge. / Dissertation (MSc)--University of Pretoria, 2011. / Anatomy / unrestricted

Trigeminal neuropathic pain (TNP) is a condition that occurs when one or more branches of the trigeminal nerve are insulted. Trigeminal neuropathic pain has been shown to be refractory to treatment. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both the peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain, however, the impact of thalamic HCN channel activity on TNP has yet to be elucidated. In this report, we used a chronic constriction of the distal infraorbital nerve (dIoN-CCI) to induce TNP in rats. By infusing HCN channel blockers into the ventral posteromedial (VPM) nucleus of the thalamus in dIoN-CCI rats, we demonstrated that inhibition of HCN channel activity ameliorated TNP. We found that the HCN blocker ZD7288 and the clinical drug ivabradine dose-dependently attenuated both evoked and none-evoked nociceptive behaviors in dIoN-CCI rats. Electrophysiological measurements showed the expression of HCN current (Ih) in the thalamocortical neurons in the VPM was sensitive to the HCN channel modulator cyclic adenosine monophosphate (cAMP), suggesting a contribution of the HCN2 subunit in thalamic HCN current. In the thalamus, surface expression of the HCN2 subunit was increased in dIoN-CCI rats. Taken together, we propose that an increase in HCN channel activity in the thalamus in the ascending nociceptive pathway contributed to trigeminal neuropathic pain.

The digastric muscle of the rabbit consists of a single anterior belly which inserts onto the lower jaw. Horseradish peroxidase was injected into the muscle and into subcutaneous regions overlying the lower jaw to determine the sites of origin of the motor innervation to both the digastric muscle and the platysma muscles. After digastric muscle injection, labelled cells were found in the ipsilateral retrotrigeminal nucleus as well as in the intermediate subnucleus of the main facial nucleus on both sides. Subcutaneous injections produced labelling which was found bilaterally in the intermediate subnucleus and in the ventromedial portion of the medial subnucleus. These results are interpreted in relation to the common embryological origin of these two muscles and their innervation.

Metastin, the product of metastasis suppressor gene KiSS-1, is proposed to be the natural ligand for the G-protein-coupled receptor GPR54, known also as AXOR12. This immunohistochemical study, using a rabbit polyclonal antiserum against the human metastin fragment (45-54)-NH2, showed that in rats metastin-like immunoreactivity (MTS-LI) was present in neurons of the nucleus of the solitary tract and caudoventrolateral reticular nucleus, and in cell processes of the spinal trigeminal tract and lateral reticular nucleus. MTS-LI was confined mainly to neurons and fibers at or caudal to the area postrema. In the spinal cord, MTS-LI cell processes formed a dense plexus in superficial layers I and II of the dorsal horn. The pattern of distribution of MTS-LI in the medulla and spinal cord suggests that this novel peptide may participate in autonomic and sensory neural signaling.

Transcutaneous auricular vagal nerve stimulation (taVNS) is a non-invasive method of activating axons in the auricular branch of the vagus nerve through the concha of the outer ear. taVNS is under investigation as an alternative treatment option for a wide range of disorders. Vagal afferent fibers terminate in the nucleus of the solitary tract (NTS) where information is processed and relayed to higher brain regions influencing sympathetic and parasympathetic systems. Due to extensive neuronal connections, it is likely that taVNS could serve as a treatment option for many disorders, specifically cardiac, migraine, and gastric motility disorders. Human fMRI studies have indicated that taVNS elicits neuronal responses within NTS and spinal trigeminal nucleus (Sp5c). Studies have indicated that caudal NTS (cNTS) has substantial connections with the cardiac system, rostral NTS (rNTS) is relevant for gastric motility, and Sp5c is likely involved in migraine disorders due to meningeal connections. Aberrant neuronal signaling is likely responsible for the development of these disorders, and taVNS has the potential to modulate neuronal activity to reestablish homeostatic signaling. In this study, electrophysiological methods were used to interrogate neuronal activity of 50-70 neurons within cNTS, rNTS, and Sp5c following taVNS. A high-impedance tungsten electrode was placed stereotaxically in 15 male Sprague-Dawley rats anesthetized with chloralose. Changes in neuronal firing rates were investigated during and immediately following taVNS by comparing changes in neuronal activity to baseline levels using the software Spike 2 v9.14. Neurons were classified as negative responders if activity decreased more than 20%, positive responders if activity increased more than 20%, or non-responders if activity changes were less than 20%. Six different taVNS parameters were investigated using three frequencies (20, 100, 250Hz) at two intensity levels (0.5, 1.0mA). Data from this study suggest that taVNS can modulate neuronal activity in a frequency and intensity-dependent manner. The greatest positive activation for all 3 brain regions occurred at 20Hz, 1.0mA stimulation where an average of 46% ± 9% neurons showed increased firing compared to 29% ± 2% positive responders for other paradigms. The greatest negative activation for all 3 regions occurred at 100Hz, regardless of intensity, where an average of 33% ± 1% neurons showed reduced firing compared to 15% ± 2% negative responders for remaining paradigms. Based on what is known about cardiac, migraine, and gastric motility disorders, it is likely that taVNS can be used to modulate activity in NTS and Sp5c to provide beneficial treatment options to patients. Specifically, using paradigms yielding decreased activity in Sp5c could improve migraine symptoms, and paradigms increasing activity in cNTS and rNTS could improve cardiac and gastric motility disorders, respectively.

Wnt signaling has been shown to have several roles in the development of sensory neurons, particularly in the ophthalmic portion of the trigeminal nerve. Many of these studies have relied on the conclusion that Wnt is necessary but not sufficient for the induction and maintenance of the neural precursor cells that develop in the ophthalmic placode. Wnt had been inhibited in the ophthalmic placode using a dominant negative t-cell factor (TCF) and resulted in the loss of Pax3 expression (indicative of undifferentiated placode cells) in all targeted cells, suggesting a loss of specification/commitment of these cells to the sensory neuron fate. This study aimed to build on that conclusion by identifying the source of Wnt signaling that allowed for the maintenance of these placode cells. To investigate this, chick embryo ex ovo cultures were used and treated with small molecule chemical Wnt inhibitors to globally knock out Wnt signaling. The embryos were then sectioned and stained for cell markers of undifferentiated placode and differentiated neural cells (Pax3 and Islet1, respectively). Also used was a conditional knockout of Porcn, a gene critical to post-transcriptional modification of the Wnt ligand, using Wnt1-cre as a driver; this allowed for the knockout of Wnt secretion from the dorsal neural tube as well as neural crest cells. The data showed a decrease in placode cell differentiation but did not indicate a necessity for Wnt in maintenance of the ophthalmic placode cells—there was no loss of Pax3 expressing cells in the ectoderm. This suggested that maintenance of the ophthalmic placode could be through alternate pathways. Data is also presented describing how loss of Porcn in Wnt1 expressing cells impacts craniofacial development, where the mouse mutant used in this study displayed the absence and underdevelopment of cranial neural crest structures.

The ophthalmic trigeminal placode (opV) exclusively gives rise to sensory neurons. A number of signaling pathways including Wnt, PDGF, FGF, and Notch are all involved in the progression of an undifferentiated cell in the opV placode to a proneural cell in the condensing opV ganglion. However, the regulatory relationships between these signal transduction pathways are still unknown. To determine if FGF activation acts to modulate Notch signaling in the sensory neurogenesis pathway, a novel multifactorial approach was employed: FGF signaling was inhibited in individual cells and globally with simultaneous inactivation of Notch signaling in chick embryos to investigate if FGF activation downregulates Notch thereby driving neurogenesis. These experiments resulted in few differentiating opV cells in the mesenchymal region of future ganglion formation suggesting an alternate regulatory relationship between FGF and Notch where either reduced Notch activity allows for FGFR4 expression (leading to FGF signaling and neurogenesis), or a parallel relationship where FGF and Notch act independently of one another to induce neurogenesis. To distinguish between these two possibilities Notch signaling was inhibited with DAPT, a gamma-secretase inhibitor, and assayed for FGFR4 mRNA expression. These results indicated FGFR4 is not upregulated by reduced Notch activity, suggesting that FGF and Notch act in parallel to promote neurogenesis. During these experiments it was observed that Notch inhibition resulted in an undefined ectoderm in the opV placode region. To investigate this, FGF and Notch were inhibited by SU5402, an FGF antagonist, and DAPT, and later sectioned and stained for Laminin. In DAPT treated embryos the basement membrane became highly fragmented, a remarkable observation not yet reported. From these data a proposed mechanism was established where activation of FGF with parallel downregulation of Notch leads to disruption of extracellular matrix proteins in the basement membrane resulting in fragmentation and subsequent delamination of differentiating opV placode cells.