## 1 Introduction  
Due to the anatomical characteristics, high vascularity, and the peculiar functions of the oral cavity, the oral mucosa is vulnerable to many insults. These include systemic diseases and the effects of autoimmune disorders, trauma from oral appliances or chewing, and local skin rashes, following exposure to systemic drug therapies, ingestion of irritating food or drink, and infectious strains [1]. Adverse stimuli can produce oral manifestations ranging from lichenoid lesions to hyperkeratosis and ulceration. Aphthous stomatitis (AS) is an ulcer disease that commonly affects the oral mucosa. It presents as painful ulcers with shallow erythematosus margins and a yellowish-grey pseudomembranous center [2]. The percentage in the world of adults affected by AS in its recurrent manifestation [(recurrent aphthous stomatitis (RAS)] is about 20%, with variations from 5% to 50%, while in children the prevalence is 39% [2,3]. AS comes in three forms, which are morphologically classified as minor aphtha or Mikulicz-ulcers, which show a diameter of 2-10 mm, major aphtha, also called mucosal necrotic periodentis or Sutton ulcers (>10 mm in diameter), and herpetiform ulcerations, which consist of multiple small ulcers [4]. No causal treatment for RAS has been developed so far; systemic and topical medications are used to reduce inflammation and pain and to support the natural period of remission [5]. Management of oral ulcers is based on the severity of the lesions and usually involves the administration of corticosteroids [5]. However, there is a lack of high-efficacy evidence for them [6], particularly for systemic interventions. The most used protocol is, therefore, a combination of topical systemic agents (colchicine, pentoxifylline, corticosteroids, dapsone, thalidomide, cyclosporine, and infliximab), a vestibular antiseptic or anti-inflammatory therapies (chloroxtidine gluconate, triclosan, amlexanox), and local anesthetics (benzocaine gel), as well as local antibiotics (tetracycline, chlortetracycline) and topical steroids (triamcinolone acetonide). Furthermore, trigger foods and acidic foods and drinks should be avoided [1,4,7]. These primarily symptomatic therapies may, however, induce side effects; steroid medications can cause candidiasis, and tetracycline or chlorhexidine mouthwashes can shorten ulcer duration but are contraindicated in children and may induce tooth discoloration [5]. Therefore, alternative treatment modalities have been developed to relieve pain and improve AS healing, such as traditional Chinese medicine [8], acupuncture [9], psychotherapy [10], and low-level/intensity laser therapy (LLLT) [11,12]. LLLT, now more correctly reported as photobiomodulation, can be considered \"a manipulation of cells' metabolism through an energy transfer by light sources of non-ablative or thermal intensity\" [12]. At the cellular level, the features of photoreceptors allow animals and humans to experience the ability to respond to light stimuli and influence the visual processes and vitamin D production. However, ubiquitous and unspecialized molecules called photoacceptors are \"in the spotlight\" because of their energetical role in the cell-light interaction [13,14]. Photons, as bosons, can transfer their energy to photoacceptors, inducing a photochemical reaction in the cell [15]. As we recently described [16], photobiomodulation is based on biological and physical-chemical evidence, where the pivotal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water and lipids.