Xerostomia: Can a Permanent Treatment Be Found at a Cellular Level?

Xerostomia, the clinical term for dry mouth, is associated with a dysfunction of the salivary glands. There are several causes of xerostomia, including radiation, chemotherapy, various systemic and autoimmune diseases, and medication. Xerostomia significantly decreases the quality of life among those with it, which is why it has been the subject of many scientific and clinical studies over the past decade.

In a recent article entitled, Xerostomia and Its Cellular Targets, published in the International Journal of Molecular Science, author Yoon-Jung Kim examines saliva secretion at a cellular level and calls for further research of the chemical processes to arrive at a more effective treatment for xerostomia than the currently existing ones. 

Background

Saliva is essential for maintaining a healthy oral environment and overall health. Saliva performs a variety of functions essential for oral and systemic health, including:

• Moisturizing and lubricating the mouth
• Enabling gustatory and olfactory sensation
• Protecting the teeth and oropharyngeal mucosa
• Facilitating speech articulation
• Allowing mastication, swallowing, and digestion
• Maintaining a balanced microbiome 

Xerostomia, defined as the subjective feeling of oral dryness, affects and is affected by the function of the salivary glands. Xerostomia can cause bad breath, dental caries and erosion, food intake problems, and even depression. According to the study, persistent xerostomia ranges between 10% and 50% of the general population. It’s more common in women (up to 30%) and older adults (up to 50%).

Components of Saliva

Salivation secretion is a complex neural and chemical process that depends mainly on parasympathetic and sympathetic nerves. In healthy humans, when a person sees or even imagines food, the salivary glands in the oral system receive a strong neural input. Neurotransmitters are released from parasympathetic nerves and bind to specific G-protein-coupled Receptor (GPCR), setting off fluid secretion. 

Healthy adults produce between 0.5 and 1.5 L of saliva per day, 90% of which is produced by the three main salivary glands, each of which produces saliva that differs in composition and characteristics:

1. Parotid (PAR): Produces saliva in response to stimuli (food, smell)
2. Submandibular (SM): Produces saliva without stimulation 
3. Sublingual (SL): Produces saliva without stimulation 

In 2020, researchers suggested a fourth set of salivary glands, the tubarial glands, responsible for saliva secretion. There are also hundreds of small salivary glands distributed

throughout the oral cavity. The glands in the lower lip are easily biopsied and

used clinically to diagnose Sjögren’s syndrome. 

Salivary cells are composed of:

• Various epithelial cells, including acinar cells, which are key components in saliva production
• Ductal cells, which transport saliva to the oral cavity
• Myoepithelial cells, which facilitate the secretion of saliva 

Causes of Xerostomia

There are five main causes of xerostomia:

• Radiation treatment of head and neck cancer: The majority of the 550,000 patients who undergo radiation treatment annually for these cancers suffer from xerostomia.
• Systemic diseases: More than 4 million people in the world have Sjögren’s syndrome, a chronic autoimmune disease, and the majority suffer from salivary gland dysfunction. Other systemic diseases associated with dry mouth include systemic lupus erythematosus, diabetes, viral infection, end-stage renal disease, sarcoidosis, and more. 
• Medications: This is the most common cause of dry mouth, with more than 400 different drugs causing xerostomia. The drugs that most often cause dry mouth are called xerogenic, and they include many different categories of medications. While drug-induced xerostomia is often reversible, the challenge is that the drugs that cause it are often prescribed for chronic conditions, such as medication for schizophrenia, heart disease, and respiratory diseases. 
• The number of medications taken: Regardless of whether individual medications cause dry mouth, there is an association between the number of medications taken and the appearance of dry mouth.
• Aging: Aging is a natural cause of xerostomia, but its incidence is compounded by taking several drugs simultaneously. Studies have shown that aging decreases the mean volume of acini by about 30% in SM glands, 25% in SL glands, and 12% in PAR glands. 

Xerostomia Treatments

As of now, there is no cure for xerostomia, though there are several short-term treatments. These are mainly directed at symptom management and relief, as well as the prevention of complications.

Systemic sialogogues are substances, often drugs, that increase the flow rate of saliva. They work by mimicking the neural signals that stimulate saliva production in the epithelial cells. Sialogogues are often accompanied by negative side effects, including nausea, diarrhea, increased urinary frequency, excessive sweating, low blood pressure, and more.

Artificial saliva or saliva substitutes are prescribed as a temporary (up to four hours) relief for dry mouth. These aim to mimic the way saliva flows, but have not been able to mimic its antibacterial properties.

Mouthwashes, rinses, and toothpaste are additional short-term treatments for xerostomia and keep the patient’s mouth, teeth, and gums healthy. 

Due to the importance of normal salivation in leading a healthy and high-quality life, further research is required to achieve a cure, or at least, better treatment options. Further examining salivation at a cellular level may be the key to a solution for xerostomia.