INTRODUÇÃO
Total saliva is a complex of secretions that come in part from the pairs
of parotid, submandibular and sublingual glands, and in part from
numerous minor salivary glands distributed in the oral mucosa (Mese,
2007). In the mouth, this compound is formed by gingival fluid,
desquamated epithelial cells, microorganisms, products of bacterial
metabolism, food residues, leukocytes, mucus from the nasal cavity and
pharynx. Saliva has several functions, including tissue repair,
buffering, protection, digestion, taste, antimicrobial action,
maintenance of tooth integrity and antioxidant defense system. (Falcão,
2013).
Saliva, as the first digestive fluid in the alimentary canal, assists in
the ingestion of food and the digestion of starch and lipids, acting as
a solvent. Saliva also plays a crucial role in hydrating and maintaining
the taste receptor and oral mucosa and protecting the teeth.
Furthermore, saliva controls oral microflora with its antimicrobial
properties and mechanical cleaning action. Therefore, the loss of
salivary function can have several serious consequences (Abueva, 2022).
The “unstimulated” flow is approximately 0.3 to 0.4mL/min but with
wide variation between subjects and is sustained presumably by minor
reflex activity and central nervous system activity since the flow of
saliva decreases during sleep to around 0.1mL/min (Proctor, 2021).
However, the speed at which saliva reaches the mouth shows great
variation between individuals (Proctor, 2016). Parasympathetic
stimulation results in increased saliva secretion through cholinergic
transmission and action on M3 muscarinic receptors, while sympathetic
stimulation alters salivary protein content through noradrenergic
transmission and action on α and β receptors (de Almeida, 2008).
Several factors are capable of altering salivary flow. Such changes may
vary from individual to individual, and in the same individual under
different circumstances. Body hydration, tobacco use, medication use,
saliva stimulation, some illnesses, among other factors, are capable of
generating changes in salivary production. (Almeida, 2008). Complaints
of dry mouth occur when there is insufficient production of saliva or
changes in its composition. Dry mouth is called xerostomia, and one of
the most common causes is due to the side effect of medications (Scully,
2003).
Drug-induced hyposalivation also can be an extension of the drug’s
intended action, as seen with the parasympatholytic agents (such as
atropine), or as an anticholinergic side effect withdrugs such as
tricyclic antidepressant (Guggenheimer, 2008). Hyposalivation is a
condition that can be very debilitating for patients and is likely to be
increasingly common, so dentists should be aware of its diagnosis and
treatment. (Mese, 2007)
Medications with anticholinergic activity can cause hyposalivation by
decreasing acetylcholine released by the parasympathetic system (Turner,
2016). Both the parasympathetic and sympathetic nervous systems
innervate the salivary glands (Guggenheimer, 2008). SNRIs are believed
to produce central accumulation of norepinephrine, activation of α2
receptors, and inhibition of parasympathetic salivary neurons in the
brainstem, resulting in decreased salivary secretion. (Proctor, 2016).
Salivary dysfunction may be accompanied by symptoms of dry mouth, called
xerostomia. The presence of xerostomia is not predictive of
hyposalivation, as both conditions can manifest independently. However,
the greater the hyposalivation, the greater the patient’s tendency to
present xerostomia (Pedersen, 2018). Reduced salivary flow is a common
disorder, and it is estimated that around 20% of the general population
has this change. (Falcão, 2013).
According to the World Health Organization (2017), mental disorders are
common and contribute to morbidity, disability, injuries and premature
mortality and increasing the risk and involvement of other health
conditions. Worldwide, it is estimated that more than 300 million
people, of all ages, suffer from depression, equivalent to 4.4% of the
world population, being more prevalent among women.
Psychiatric medications can cause side effects with repercussions on the
stomatognathic system, such as hyposalivation (Kossioni, 2013). Patients
who use medication for a long time experience side effects with
repercussions on the oral cavity, for example, on the salivary glands,
altering the flow and composition of saliva (de Ameida, 2012). It is
worth mentioning that side effects represent one of the main reasons for
discontinuing treatments (Bull, 2002).
A study analyzed medications and observed ten out of 15 antidepressants
showed significantly higher rates of short-term dry mouth than placebo,
with the following decreasing order of incidence: duloxetine,
desvenlafaxine, reboxetine, venlafaxine, sertraline, bupropion,
paroxetine, escitalopram, levomilnacipran and fluvoxamine. Five out of
15 antidepressants (agomelatine, citalopram, fluoxetine, mirtazapine and
vortioxetine) did not differ from placebo in terms of dry mouth rates
(Oliva, 2021). In another bibliographic survey it was reported fifty-six
medications showed strong evidence of interference with the function of
the salivary glands, thirty-six of which belonged to the main nervous
system category of the ATC (Anatomical Therapeutic Chemical), and the
most cited in the literature are oxybutynin (21 articles), tolterodine
(19 ), duloxetine (19), quetiapine (14), bupropion (12), olanzapine
(11), solifenacin (11), clozapine (9), fluoxetine (9) and venlafaxine
(8) (Wolff, 2017).
Fluoxetine is an effective antidepressant when administered in dosages
of 20 to 80 mg per day (60 to 80 mg being clinically usual) for patients
with unipolar depression (Benfield, 1986). The approved dose range is up
to 80 mg/day, and when higher doses are used, adverse events are more
common (Wernicke, 2004). Adverse events commonly associated with the
initiation of fluoxetine therapy tended to decrease, and no adverse
events reported initially became more frequent at the end of therapy
(Zajecka, 1999). Dysgeusia has been reported following administration of
fluoxetine (Wolff, 2017).
Clinical signs of dry mouth, identified during a physical examination,
include glossy oral mucosa, altered gingiva, fissured tongue or loss of
lingual papillae, and foamy saliva. Once a diagnosis is made and an
underlying etiology is identified, there are many therapeutic options
for management that can help alleviate the clinical manifestations of
xerostomia (Millsop, 2017).
The theory of stimulated emission was first described by Einstein in
1917. The word LASER is the acronym for “Light Amplification by
Stimulated Emission of Radiation” (Genovese, 2007).
The mechanisms involved in the treatment of PBM are not yet completely
understood. However, the main idea is that photons are absorbed by the
target tissue, converting them into useful energy that enhances
metabolic processes in the cell, such as increased ATP production and
the production of reactive oxygen species (ROS) (Sousa, 2019).
Low-power laser light therapy has been shown to be effective in the
treatment of the most diverse conditions or diseases, as it promotes
biomodulation of cellular metabolism, analgesia and anti-inflammatory
effects, without mutagenic and photothermal effects (Gonelli, 2016). Its
effects are based on transforming laser light into biomodulatory energy
(Saleh, 2014).
The photobiomodulation effect depends on the number of absorbed photons
which is correlated to the wavelength, the photon delivery rate (power)
and the correct selection of spectrum and time parameters (Schubert,
2007). There is some research on the use of photobiomodulation to
recover salivary glands and increase salivary flow. However, there is
great variability between studies according to the photobiomodulation
light parameters used and therefore results are rarely comparable
(Golez, 2022). The wavelength used in low-level laser therapy is not
fixed, so it is worth studying the laser equipment and defining the
wavelength indicated for therapeutic efficacy. (Xu, 2015).
Photobiomodulation, previously called low-intensity light therapy
(LLLT), is a method in which radiation power is generally between 0.05
and 0.5 W to avoid thermal or cytotoxic effects on tissue (Huang 2009,
Sousa 2019). Low-power laser is an efficient agent for attenuating
salivary hypofunction (Gonelli, 2016).
Laser and LED light induce a photobiomodulation (PBM) effect that is
used to accelerate healing by increasing cell viability by stimulating
ATP synthesis by mitochondrial photoreceptors and the cell membrane
(Dompe, 2020). Wavelength of 810 nm can be absorbed by the chromophore
cytochrome c-oxidase and other chromophores to improve mitochondrial
activity. The cytochrome c-oxidase activity increases the accumulation
of mitochondrial activity, which leads to greater ATP production. (Wang,
2017)
Studies have shown that photobiomodulation has been widely used to
improve the functionality of the major salivary glands, as well as
salivary flow. Different in vivo protocols react differently to light
depending on various radiometric parameters and systemic condition
(Loncar, 2011; Fidelix, 2018)
Despite different photobiomodulation methods, it is known that modified
ILIB (Intravascular Laser Irradiation Blod) therapy has been studied
since 1981 by Soviet scientists (Karu, 1998). The proposal with ILIB was
the control of cardiovascular physiology, through the delivery of red
laser therapy (660nm), through an optical fiber in the arteries or
vessels, crossing the skin and introducing it into the blood vessel to,
there, deposit the irradiation of a laser with 3 to 5mW of power for 20
to 30 minutes. Researchers realized in 1981 that in the heart attack
area, sudden deaths decreased, because red laser therapy had probably
photo-switched off nitric oxide from hemoglobin molecules and thus
induced relaxation of the vessel walls and improved blood flow and
tissue oximetry. The wavelength chosen for intravenous irradiation will
influence the benefits reaped. Irradiation in the infrared spectrum
(above 800 nm) accelerated the release of oxygen, while wavelengths
between 630-670 nm promoted improvement in the transport of oxygen from
the blood (Xu, 2015).
The change in the name of ILIB to Vascular Systemic Photobiomodulation
(Hamblin, 2016), is more suitable for the process where light sources,
lasers or LEDs, are used to deposit photonic energies, previously
determined, on the skin, in the place where large blood vessels
(arteries or veins) have their greatest projection towards the skin, and
then evolving towards transmucosal applications, where we find a large
concentration of blood vessels, that is, in the intranasal region and/or
the mouth floor – sublingual.
Vascular photobiomodulation therapy promotes the absorption of red
wavelength light by the blood, causing an increase in metabolism and
synthesis of the enzyme superoxide dismutase, the main physiological
protein regulating the body’s oxidative system. Superoxide dismutase
inhibits the action of reactive oxygen species (ROS), leads to the
protection of cells against mutations by fighting free radicals.
Therefore, the therapy aims at the functional recovery of the
antioxidant enzymatic system, maintaining the balance of the organism as
a whole, providing functional optimization of each system (Chamusca,
2012).
PBM to stimulate salivary production by the glands is not yet a
consensus in the literature (Sousa, 2019), however there are already
studies that report a significant increase (Gonelli 2016; Saleh, 2014,
Loncar, 2011), and PBM in the salivary glands is safe, well tolerated
and there are no reports of incidents or deleterious effects of the
therapy (Sousa, 2019).
Furthermore, vascular photobiomodulation directly or indirectly affects
an organism’s immune cells, hormones, and metabolic processes, thereby
improving not only the function of the vascular system, but also the
body’s other systems (Mikhaylov 2015).
One of the side effects of medications indicated for psychiatric
treatment is hyposalivation or xerostomia. In search of treatments to
reduce discomfort, PBM is one of the alternatives that has proven to be
effective. This article aims to demonstrate the clinical improvement of
a patient with severe xerostomia after treatment with vascular PBM, so
that further studies in the area are possible and dosimetric parameters
are defined.