Device and method for stimulating salivation

Surgery: light – thermal – and electrical application – Light – thermal – and electrical application – Electrical therapeutic systems

Reexamination Certificate

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C607S116000, C607S072000, C607S134000

Reexamination Certificate

active

06230052

ABSTRACT:

FIELD AND BACKGROUND OF THE INVENTION
The present invention relates to a device and method for stimulating salivation, and more particularly, to an implantable device and a method of using same for stimulating salivation by the application of electrical energy to nerves in the region of the oral cavity to produce salivation by reflex action, by creating parasympathetic outflow to the salivary glands, parotid, submandibular or sublingual.
The following background information is derived, in part, from A. D. Korczyn, Ed. “Handbook of autonomic nervous system dysfunction” Marcel Dekker, N.Y., 1995, pp. 293-309.
Salivary glands have been recognized since the 19
th
century as typical effector organs of the autonomic nervous system. The classic experiments of Pavlov are a good example of the interest that salivary glands have stirred up among scientists. They illustrate the decisive control the autonomic nervous system exerts on salivary gland. Therefore, salivary glands are sensitive markers of autonomic nervous system function and, as such, may present a variety of disorders related to autonomic nervous system dysfunction.
Applied Anatomy of the Salivary Glands: Human beings possess three pairs of major salivary glands—parotid, submandibular, and sublingual—and a myriad of minor salivary glands spread throughout the oral mucosa. All salivary glands share a common parenchymal structure of acinar units and ducts. The former are composed of acinar cells encircled by myoepithelial cells and circumscribing the acinar lumen. The acinar lumen drains into the ductal system, which reaches the oral cavity. The salivary gland stroma is made up of neurovascular structures and scarce connective tissue.
The salivary gland morphology will be described succinctly here. The parotid glands, the largest of the salivary glands, lie underneath the skin of the cheeks. They secrete their saliva via Stensen's ducts, which open into the oral cavity opposite the upper second molars. Parotid glands have predominantly serous acini, and therefore the fluid they secrete is “watery” and not viscous, as is the fluid secreted by mucous glands.
Innervation of the parotid glands is provided by parasympathetic and sympathetic fibers. The preganglionic parasympathetic fibers of the parotid glands arise from the inferior salivary nucleus in the medulla, from where they travel through the glossopharyngeal nerve, the tympanic nerve and plexus, and the lesser petrosal nerve into the otic ganglion. Here they synapse with fibers in the auriculotemporal nerve, reaching the parotid gland. The sympathetic innervation originates in the superior cervical ganglion, and contacts the parotid gland via the plexus of the external carotid.
The submandibular glands are the second largest salivary glands. These glands and the sublingual glands are situated at the floor of the mouth. These glands empty their secretions into the oral cavity through ducts whose foramina are located sublingually. While submandibular glands have a mixed structure of serous and mucous secretory units, sublingual glands are mainly mucous.
The innervation of submandibular and sublingual glands is similar. Preganglionic parasympathetic innervation originates from the superior salivary nucleus in the pons, reaching the submandibular ganglion after passing along the nervus intermedius (facial nerve) and the chorda tympani. The sympathetic innervation arises from the superior cervical ganglion and reaches the glands by way of the facial artery plexus.
Secretion of Saliva: The greatest part of saliva is secreted by the parotid and submandibular glands. Other contributions to saliva include sublingual and minor gland secretions, gingival exudate, desquamated epithelial cells, blood cells, microorganisms, and their products.
Saliva performs a crucial role in the oral cavity. The full accomplishment of salivary functions depends on proper salivary flow rate and composition. Taste perception is facilitated by saliva carrying food particles onto the taste buds in an appropriate dilution. Salivary amylase and lipase start the digestion of starch and fat. Saliva is also important in the formation of the food bolus and the salivary lubricatory glycoproteins permanently coat oral surfaces, assisting in food mobility and reducing friction between the different oral structures (teeth, tongue, cheeks, lips) and between the structures and foreign elements (food, dental prostheses).
Salivary lubrication, repair, lavage, antimicrobial, and buffering properties contribute significantly to the maintenance of oral hard and soft tissue integrity.
The secretion of saliva is regulated by the autonomic nervous system, with a minor role played by hormones and autocoids. Salivary secretion fluctuates between minimal and maximal rates. The basal secretion of saliva, which is due to the spontaneous activity of the salivary nuclei, displays a circadian rhythm of high amplitude.
The stimuli that enhance salivation are related to eating: tasting, smelling or seeing food, and chewing. These peripheral stimuli are transmitted to the central nervous system, exciting efferent salivary fibers. During meals saliva production rises 5-50 fold over basal secretion.
The accumulated knowledge on salivary gland physiology, which is mostly based on studies performed on animals, explains the role of the autonomic nervous system in saliva secretion. The two autonomic divisions act synergistically to produce salivation by the salivary glands, although sublingual and labial salivary glands lack sympathetic control.
In the parotid and submandibular glands the parasympathetic system is mostly responsible for the water and electrolyte secretion, whereas the sympathetic system mainly regulates the protein (e.g., amylase) secretion.
Autonomic Effects on Acinar Secretory Cells: Postganglionic sympathetic fibers release norepinephrine, which activates alpha- and beta-adrenergic receptors on salivary glands. The parasympathetic fibers release acetylcholine, vasoactive intestinal peptide (VIP), and substance P. Beta-adrenergic and muscarinic cholinergic receptors are present at a much higher density on parotid membranes than other receptors.
The signal transduction mechanisms differ among the salivary gland receptors. Beta-adrenergic and VIP receptors activate adenylate cyclase that catalyzes cAMP formation from ATP. Conversely, alpha-2-adrenergic receptor activation blocks cAMP generation and inhibits salivary secretion. Muscarinic cholinergic, alpha-1-adrenergic, and substance P receptors activate phospholipase C, and, as a result, diacylglycerol (DAG) and inositol triphosphate (ITP) are formed from the hydrolysis of phosphatidylinositol-4,5-biphosphate.
Each second messenger created by the transduction mechanisms mobilizes its own pathway. Signaling of cAMP leads primarily to exocrine protein secretion. DAG likewise induces protein excretion, but to a much lower extent. The pathway of ITP involves calcium mobilization, which causes fluid secretion through the activation of ion channels. Unlike the pancreas and the kidney, fluid production by salivary gland does not depend upon perfusion pressure but on the creation of osmotic pressure by active ion transport across the acinar cells into the lumen. This osmotic pressure drags water from the interstitium into the acinar lumen to produce an isotonic fluid, termed promary saliva.
Autonomic Effects on other Salivary Gland Components: Myoepithelial cell contraction, which contributes significantly to saliva secretion, is induced by parasympathetic and sympathetic stimulation, acting upon muscarinic cholinergic and alpha-adrenergic receptors, respectively.
Primary saliva fluid, secreted from acinar cells, is modified in the ductal system to produce a hypotonic fluid, which is secreted into the oral cavity. Sodium and chloride are reabsorbed into ductal epithelial cells, which, in turn, release potassium and bicarbonate ions. A short contact time of primary saliva with ductal cells, which occurs when salivary flow increases upon salivary gland stimulation, diminishes

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