Science background

Recently, missions planned to Mars from 2001 until now have been expected to require 18–24 months of exposure to microgravity conditions, which might have severe effects on human physiology, including that of the oral cavity. The changes were mentioned in previous studies (Ongole, Reference Ongole2009).

Human physiological adaptation to space is challenging in human space flight. Astronauts will encounter physiological and psychological alterations during the journey when they return to the earth. Exposure to microgravity and the space environment, even over a short or long period, affects human health (Anuradha and Grover, Reference Anuradha and Grover2010).

These effects include neurovestibular problems, involving space motion sickness, disorientation, impaired balance, neuromuscular coordination, fluid retention, orthostatic hypotension, ventricular arrhythmias, reduced cardiac muscle mass, atrophy of muscles, sleep disorders, immune-related problems such as infection and immunodeficiency, psychological effects, temporomandibular joint dysfunction (TMD) and dysfunction of masticatory muscles associated with pain including in the oral cavity. Very few studies have been published on the effect of microgravity on the oral cavity. However, it has been reported that microgravity increases the prevalence of periodontitis, dental caries, periodontal bone loss, fracture of the jawbone, pain, dysesthesia in the teeth and oral cavity tissue, salivary duct stones and oral cancer. The aim of the study was to analyse all the literature regarding microgravity and management of complications of the head and neck among astronauts.

General methodology

To identify all the records related to the effect of microgravity, we performed a systematic review of articles published in PubMed, EMBASE, Cochrane, SciELO, Google Scholar and NASA about microgravity and oral maxillofacial diseases through 2020. The following search terms were combined in the searches: oral maxillofacial OR head and neck OR oral cavity OR oropharynx AND microgravity AND astronomy AND Nasa AND Mars mission, with no limitation on the year of publication. Additional studies from the reference lists of selected articles were included by manual search. A total of 467 articles were found. EndNote software was used to remove duplicates of the same article in more than one database. Alerts according to the PRISMA guidelines were used to maintain an ongoing list of the literature and after removing duplicate records, 83 articles remained. After the full-text articles were assessed for inclusion eligibility, 47 articles were found to be published in foreign languages and 12 were editorials. Ten scientific documents directly related to microgravity and Oral and Maxillofacial Surgery were assessed. Two reviewers independently screened the titles and abstracts of the identified citations. Full texts of the citations were assessed. Data extraction from individual studies included the name, year of publication and study design.

Microgravity and its effect on bone formation

Bone loss is considered to be one of the most serious and potentially intractable biomedical consequences of human space flight. However, microgravity-induced changes in bone are not uniform along the skeletal axis. For instance, while bone mineral density (BMD) decreases in the lower extremities, it increases in the skull. A similar pattern of region-specific changes in bone properties has been reported to occur with head-down bed rest (Bohra et al., Reference Bohra, Bohra and Bohra2019; Nordin et al., Reference Nordin, Need, Morris and Horowitz1993; Vermeer, Reference Vermeer1997; Zhang et al., Reference Zhang, Ma, Gao, Gu and Fu1999).

Studies on the effects of spaceflight on human health are of great importance to develop effective steps to prevent bone loss and other changes induced by microgravity or the spaceflight environment. Bone loss has been mentioned for many years in the metric system, μg (1–2% a month). Increased bone loss and risk of fractures is an identified risk in the bioastronautics critical roadmap for long-term missions to the moon and mars (Bohra et al., Reference Bohra, Bohra and Bohra2019; LeBlanc, Reference LeBlanc1992; Nordin et al., Reference Nordin, Need, Morris and Horowitz1993; Vermeer, Reference Vermeer1997; Zhang et al., Reference Zhang, Ma, Gao, Gu and Fu1999). Exposure to the μg environment of space causes astronauts to lose calcium from bones. This loss occurs because the absence of Earth's gravity disrupts the process of bone maintenance in its primary function of supporting body weight. Exposure to the μg environment of space causes men and women of all ages to lose up to 1% of their bone mass per month due to lack-of-use atrophy, a condition similar to osteoporosis. There are, indeed, four major bone cell types and each of them seems to be influenced by μg. Bone mesenchymal stem cells (MSCs) are able to differentiate into adipocytes, osteoblasts and osteoclasts. Proliferation and differentiation are very sensitive to μg due to the lack of gravity in space (Nordin et al., Reference Nordin, Need, Morris and Horowitz1993).

In space, mechanical stress is reduced, leading to a decreased rate of osteogenesis and an increased adipogenesis rate. Osteoblasts are derived from MSCs, but in μg the differentiation process does not occur properly and the resulting bone loss has been attributed to osteoblasts due to their (1) reduced proliferation and activity, (2) reduced differentiation and (3) decreased response to bone-related factors in the microenvironment. Observations have also been made regarding the cytoskeleton of osteoblasts; there is growing evidence that the cytoskeleton is closely connected to nuclear morphology and that the enlarged nuclei observed in flight osteoblasts could be a result of cytoskeletal disruption (LeBlanc, Reference LeBlanc1992; Paloski et al., Reference Paloski, Black, Reschke, Calkins and Shupert1993; Rai et al., Reference Rai, Foing and Kaur2012). The osteocytes in cortical bone and periosteum degenerated after a 12.5-day flight in space on the Cosmos Biosatellite [osteocyte apoptosis has been observed after a 2-week flight, increasing the number of functionally active osteoclasts]. Apoptotic osteocytes are essential for the initiation of bone remodelling (LeBlanc, Reference LeBlanc1992; Paloski et al., Reference Paloski, Black, Reschke, Calkins and Shupert1993; Buckey et al., Reference Buckey, Lane, Levine, Watenpaugh, Wright, Moore, Gaffney and Blomqvist1996; Rai et al., Reference Rai, Foing and Kaur2012), although bone formation was shown to be reduced after 7–19 days of spaceflight; this effect may be mediated in part by the flight-induced increase in glucocorticoid secretion. In different studies, 17 days of spaceflight was associated with reduced osteoblast recruitment in specific weight-bearing rat bone, which occurred independently of endogenous glucocorticoid status (Paloski et al., Reference Paloski, Black, Reschke, Calkins and Shupert1993; Baldwin et al., Reference Baldwin, White, Arnaud, Edgerton, Kraemer, Kram, Raab-Cullen and Snow1996; Buckey et al., Reference Buckey, Lane, Levine, Watenpaugh, Wright, Moore, Gaffney and Blomqvist1996; White and Averner, Reference White and Averner2001; Rai and Kaur, Reference Rai and Kaur2013a). Researchers have predicted that the decrease in blood and plasma volume and flow into the lower extremities of humans during spaceflight would result in a shift in the balance between deposition and resorption of bone such as that bone mass would be reduced (Moore and MacDougall, Reference Moore and MacDougall2010; Rai et al., Reference Rai, Kaur and Foing2011b; Rai and Kaur, Reference Rai and Kaur2013b; Goyal et al., Reference Goyal, Malhotra, Bansal, Arora, Arora and Singh2015; Philippou et al., Reference Philippou, Minozzo, Spinazzola, Smith, Lei, Rassier and Barton2015). Mechanical stress generated by weight-bearing appears to regulate skeletal remodelling. Bassett and Becker suggested that the cell-mediated coupling of bone formation and resorption may be regulated by an electrical signal generated by bearing weight (Hudson, Reference Hudson1969; Hinsenkamp et al., Reference Hinsenkamp, Burny, Bourgois and Donkerwolcke1981; Simmons et al., Reference Simmons, Grazman, Russell, Walker, Bikle and Morey1983; Rai et al., Reference Rai, Kaur and Foing2011b). A cellular uncoupling due to a localized alteration in the surrounding bone appears to be a likely aetiology of site-specific osteopenia and could lead to increased serum calcium and a secondary decrease in PTH secretion and 1,25-(OH)2D production (Hudson, Reference Hudson1969; Hinsenkamp et al., Reference Hinsenkamp, Burny, Bourgois and Donkerwolcke1981; Simmons et al., Reference Simmons, Grazman, Russell, Walker, Bikle and Morey1983; Colleran et al., Reference Colleran, Wilkerson, Bloomfield, Suva, Turner and Delp2000; Mongini et al., Reference Mongini, Ciccone and Ibertis2000; Korszun et al., Reference Korszun, Young, Singer, Carlson, Brown and Crofford2002; Nishikawa et al., Reference Nishikawa, Ohgushi, Tamai, Osuga, Uemura, Yoshikawa and Myoui2005; Moore and MacDougall, Reference Moore and MacDougall2010; Rai et al., Reference Rai, Kaur, Foing and O'Griofa2011a; Rai et al., Reference Rai, Kaur and Foing2011b; Rai and Kaur, Reference Rai and Kaur2013b; Ulbrich et al., Reference Ulbrich, Wehland, Pietsch, Aleshcheva, Wise, van Loon, Magnusson, Infanger, Grosse, Eilles, Sundaresan and Grimm2014; Goyal et al., Reference Goyal, Malhotra, Bansal, Arora, Arora and Singh2015; Philippou et al., Reference Philippou, Minozzo, Spinazzola, Smith, Lei, Rassier and Barton2015).

Head and neck barotrauma

Based on the Boyles Law, the surrounding pressure of gas volume varies inversely at a constant temperature and the gas volume in the body's rigid cavities is associated with atmospheric pressure, in which changes in pressure may lead to several adverse effects known as barotrauma (Hodges, Reference Hodges1978). Barotrauma may occur during hyperbaric oxygen therapy, diving or flying; head and face barotrauma include barotitis-media, barosinusitis, barotrauma-related headache, barodontalgia and dental barotrauma. The variation in the volume of the gas inside the body's rigid cavities, which is linked with the variation in atmospheric pressure, causes several harmful effects. This variation may lead to various conditions, such as barotitis media, barosinusitis, barotrauma-related headaches, dental barotrauma and barodontalgia (Moore and MacDougall, Reference Moore and MacDougall2010).

Head and face barotrauma include external otitic barotrauma, barotitis-media, barosinusitis, barotrauma-related headache, dental barotrauma and barodontalgia. External otitic barotrauma occurs as a result of injury to the lining of the mucosa of the external ear canal; the process of stripping the epithelial layer may be accompanied by pain (Sognnaes, Reference Sognnaes1946). The rigid cavity of the middle ear space is ventilated by the one-way fluttered auditory (eustachian) tube, which is opened by the simultaneous contraction of the tensor veli palatini and salpingopharyngeus muscles, in a positive air pressure gradient between the outer ear space and the middle ear space, as well as during swallowing or yawning. However, during rapid descent, the negative pressure developed in the middle ear is usually not resolved spontaneously. As a result, a partial vacuum is created and later vascular engorgement, as well as haemorrhage, may occur. The gradient is eventually relieved by the transudation of serum. Some symptoms of barotitis media include ear discomfort, intense pain, vertigo with nausea and tinnitus (Hodges, Reference Hodges1978).

During the descent from high altitudes, a partial vacuum develops, which is manifested by a retracted tympanic membrane leading to barotitis and barosinusitis (Kennebeck et al., Reference Kennebeck, Knudtzon and Goldhush1946). Barosinusitis is an inflammation of the paranasal air sinuses, whereas acute inflammation of the middle ear cavities and inflammation of the sinuses cause barotrauma. The vacuum created due to air pressure difference causes mucosal oedema, dizziness, headache and anoxia (Ingle and Glick, Reference Ingle and Glick1994). Pain and numbness can also be sequelae of the pressure exerted on branches of the fifth cranial nerve (Moore and MacDougall, Reference Moore and MacDougall2010); the dental relevance of non-dental head and face barotraumas is as follows (Rai, Reference Rai2007). Either barotitis media or barosinusitis can occur and can manifest as toothache (Garges, Reference Garges1985). Several reports have shown a relationship between eustachian tube dysfunction and dental malocclusion (McDonnell et al., Reference McDonnell, Needleman, Charchut, Allred, Roberson, Kenna and Jones2001).

Masticatory muscles

Under microgravity conditions, the muscle mass decreases, which results in a small increase in muscle tonicity in difficult situations. Muscles will, in general, become feeble as they are used less often against the power of gravity (Oganov et al., Reference Oganov, Rakhmanov, Novikov, Zatsepin, Rodionova and Cann1991). Therefore, muscle loading is an important factor in maintaining muscle mass; atrophy is unavoidable when the load is removed. Nevertheless, masticatory muscles do not lose mass in clinical conditions such as myopathy requiring critical care. The properties of masticatory muscles can, therefore, be harnessed to conserve mass (Alomar et al., Reference Alomar, Medrano, Cabratosa, Clavero, Lorente, Serra, Monill and Salvador2007). Mandible elevator muscles that act against gravitational forces, such as the masseter, temporalis and medial pterygoid, are more vulnerable than their counterparts (Smith et al., Reference Smith, Nillen, LeBlanc, Lipton, Demers, Lane and Leach1998). Philippou and coworkers performed a 13-day clinical test on two groups of mice; one of them was onboard a space shuttle and the other stayed on Earth. The mice were maintained on a specific nutritional plan, which was mainly a solid base. In the case of the tibialis anterior in the flight group, primary indications of atrophy were detected; they exhibited decreased muscle mass, decreased phosphorylated (P)-act and increased oestrogen expression. On the other hand, a slight alteration was found in the case of the masseter and they had no significant change in mass but an increase in P-focal adhesion kinase, an increase in P-Akt and lower oestrogen production relative to limb muscles that were unaltered in microgravity (44). This proposed constant stacking of the masseter under microgravity conditions was expected to restrict disuse degeneration, as cheek muscles were continuously being used (Smith et al., Reference Smith, Nillen, LeBlanc, Lipton, Demers, Lane and Leach1998; Alomar et al., Reference Alomar, Medrano, Cabratosa, Clavero, Lorente, Serra, Monill and Salvador2007).

The investigators explored the topic further, resulting in an intriguing finding. The trial was repeated once again on the same group of mice, only this time, the mice consumed a liquid diet. The masseter muscle remained healthy in the flight group unlike the tibialis anterior. Continuous loading microgravity prevents atrophy, yet masticatory muscles have a different set point that simulates disuse appendicular muscle atrophy (Alomar et al., Reference Alomar, Medrano, Cabratosa, Clavero, Lorente, Serra, Monill and Salvador2007). This suggests that various muscles have diverse ‘set points’ for adapting, so it was concluded that masticatory and cheek muscles hold up better in space than leg muscles (Smith et al., Reference Smith, Nillen, LeBlanc, Lipton, Demers, Lane and Leach1998; Alomar et al., Reference Alomar, Medrano, Cabratosa, Clavero, Lorente, Serra, Monill and Salvador2007).

Temporomandibular joint

All procedures and mechanisms beginning from bone formation, new bone deposition and mineralization are reduced or stopped during weightlessness due to the reduced mechanical pressure exerted on bones and joints, which results in porous bones and eventually bone loss (Gibbons, Reference Gibbons2003; Nagaraj et al., Reference Nagaraj, Nigam, Gogula, Sumana and Saxena2018). In the context of bone loss, the mineral mass of the bone is reduced, leading to bone weakness and predisposition to fracture. In such situations, skeletal muscle support is also not needed to maintain body posture, which weakens these muscles (Nagaraj et al., Reference Nagaraj, Nigam, Gogula, Sumana and Saxena2018). The temporomandibular joint (TMJ) is the most perplexing joint in the human body and enables the hinging motion of the mandible in one plane and simultaneously enables sliding movement; consequently, the TMJ is referred to as the ginglymoarthroidal joint (Rai and Kaur, Reference Rai and Kaur2013b). The TMJ comprises the temporal bone, the mandibular condyle and an articular plate and is classified as a compound joint. It is encompassed by facial musculature, tendons and ligaments, which permit its function (Whedon, Reference Whedon1984). The circadian rhythm of the body is affected by microgravity conditions and is associated with physiological changes; psychological stress also increases, resulting in sleep disturbances (Rambaut and Goode, Reference Rambaut and Goode1985). This stress legitimately influences the temporomandibular construction as well as the general decrease in bone mineral mass of the complete body (Oganov et al., Reference Oganov, Rakhmanov, Novikov, Zatsepin, Rodionova and Cann1991). Temporomandibular disorders (TMDs) have multifactorial aetiologies and can involve sleep disorders and stress due to microgravity. Higher levels of psychological distress among the TMJ and skeletomuscular muscle groups are prone to being influenced by psychological domains, with lower levels of TMJ pain than muscle pain. Additionally, quality of sleep and stress levels are associated with TMDs. TMDs are a common stress-related condition that are associated with dysregulation of cortisol and melatonin secretion. Increased activation of the stress hormone axis by conscious pain perception is a likely explanation, but the magnitude of the increase could indicate that pain in the facial region acts as a greater stimulus than pain elsewhere in the body. TMDs have multifactorial aetiologies with observed associations with sleep disorders and stress due to extreme conditions during simulated Mars missions (Rambaut and Goode, Reference Rambaut and Goode1985; Oganov et al., Reference Oganov, Rakhmanov, Novikov, Zatsepin, Rodionova and Cann1991). Regarding masticatory muscles, all the available literature demonstrated higher stiffness in spaceflight. Masticatory muscles, such as temporal muscles and the masseter muscles, are the two main muscles of mastication. The effect of stress directly affects the temporomandibular architecture along with the loss of mineral density of the body (Whedon, Reference Whedon1984; Rambaut and Goode, Reference Rambaut and Goode1985).

The TMJ is the most complex joint and it provides a hinging movement on one plane. Anomalous facial appearance, loss of pain impression and temperature sensation and diminished tongue and mandibular movement due to microgravity conditions were demonstrated as a result of the fluid shift mechanism. In the microgravity state, along with psychological stress, sleep disturbance also increases, activating the automimic nervous system hypothalamus, which causes fibres of the muscle spindle to contract and increases muscle tonicity. In the case of microgravity, there is a reduction in muscle mass during a stressful period. For this reason, the impact on the TMJ experienced by astronauts is more mental than physiological (44). In longer span space travel, a decrease in the concentration of circling parathormone causes a reduction in vitamin D metabolism. The impact on complete body homeostasis influences disruption of TMJ action. These problems tend to increase with prolonged missions and regular travel (Smith et al., Reference Smith, Nillen, LeBlanc, Lipton, Demers, Lane and Leach1998). Space flight-induced bone loss has resulted in health risks among astronauts in recent decades; however, the process is still unclear and it is still a topic that is not well understood. Future study is needed.

Some actions, such as exercise, adequate intake of calcium and vitamin D supplements and appropriate body hydration, are suggested to counteract the danger of metabolic loss caused by space flying (Vermeer, Reference Vermeer1997). However, bone resorption and joint dysfunctions occurring during space travel have been revealed as critical health dangers for astronauts in recent decades and these factors have oral and maxillofacial effects; microgravity is also a subject that is not well understood and requires further investigation. Overcoming these issues will empower human investigation missions and enhance crew security (Zhang et al., Reference Zhang, Ma, Gao, Gu and Fu1999).

Barodontalgia

Barodontalgia is a kind of oral pain caused by a change in barometric pressure in an otherwise asymptomatic organ. The occurrence of pain as a result of changing pressure depends on the related pathology (Philippou et al., Reference Philippou, Minozzo, Spinazzola, Smith, Lei, Rassier and Barton2015). Barodontalgia is a symptom and not a pathologic condition itself. Normally, barodontalgia is an exacerbation of preexisting subclinical oral disease (Lakshmi, Reference Lakshmi2014). It occurs due to the entrapment of gases in the closed chamber because it is unable to adjust to the internal pressure (Sognnaes, Reference Sognnaes1946). Pain occurring on descent is related to facial barotrauma or pulp necrosis and pain occurring on the ascent is related to the vital pulp tissue. Pain occurring on both ascent and descent are related to periapical disease (Lakshmi, Reference Lakshmi2014). Reduction in atmospheric pressure, in the context of direct barodontalgia, causes an effect on the affected tooth and, in the context of indirect barodontalgia, stimulation of the superior alveolar nerves at the time of maxillary barosinusitis can cause pain. Pain in teeth can occur due to the stimulation of nociceptors in the maxillary sinus (Lakshmi, Reference Lakshmi2014).

Barodontalgia can occur as a result of defective tooth restorations, pulp necrosis, dental caries, periodontal pockets, mucous-retention cysts, impacted cysts and dental caries (Ongole, Reference Ongole2009). Pulp/periapical conditions and symptoms can classify barodontalgia into 2 types: pulp/periapical-related direct barodontalgia and barotitis/barosinusitis-induced ‘indirect’ barodontalgia (Anuradha and Grover, Reference Anuradha and Grover2010).

Microgravity effects on cervical and vertebral bone

Since space studies are limited, knowledge of the effects of long-duration space flight and microgravity is limited. Lower extremity skeletal muscle atrophy has been mentioned in the context of long-term spaceflight and gravity-induced muscle degradation; one of the most common spinal injuries is a herniated nucleus pulpous disc. Herniation is 4.3-times more likely in space flight conditions than in normal conditions. The combination of spaceflight-induced loss of muscle strength and sensorimotor impairment reduce postural stability. Bone loss results in a higher likelihood of injury during the dynamic loading encountered in spacecraft landings (Ulbrich et al., Reference Ulbrich, Wehland, Pietsch, Aleshcheva, Wise, van Loon, Magnusson, Infanger, Grosse, Eilles, Sundaresan and Grimm2014).

Astronauts are prone to sarcopenia, increased fatigue levels and decreased muscle strength. Research has shown that microgravity results in a decrease in type I and II myofibres. Further studies should include assessments of changes in vertebral disc height, cervical curvature, vertebral bone density and cortical thickness (Oberholzer et al., Reference Oberholzer, Siebenmann, Mikkelsen, Junge, Piil, Morris, Goetze, Meinild Lundby, Nybo and Lundby2019).

Exercise plays a key role in maintaining astronaut health and fitness while in space. Protein and its components (amino acids) are essential for all body chemical reactions, structure and muscles. In spaceflight, total body protein turnover increases, as measured by the loss of the orally ingested stable isotope. Glycine is an amino acid that is found abundantly in proteins, so changes in blood levels indicate the amount of glycine moved to the tissues for protein synthesis. Some of the changes may be due to the catabolic state of weight loss found in many astronauts due to lower-than-needed energy intakes. The stress of spaceflight found in astronauts may increase protein breakdown. Increased stress was reflected by increased levels of blood and urinary cortisol. Dietary protein levels are already high during spaceflight. Protein recommendations are the same as those of ground-based dietary recommendations (Oberholzer et al., Reference Oberholzer, Siebenmann, Mikkelsen, Junge, Piil, Morris, Goetze, Meinild Lundby, Nybo and Lundby2019).

Sleep disorders

It has been reported that a heavy workload, international environs (different traditions, languages and habits), restricted internet access, poor diet and insufficient supplies result in stress in the simulated Mars mission (Nordin et al., Reference Nordin, Need, Morris and Horowitz1993). The human physiological status will change in response to microgravity and certain parameters, as mentioned earlier, result in extreme conditions (Vermeer, Reference Vermeer1997; Zhang et al., Reference Zhang, Ma, Gao, Gu and Fu1999; Alomar et al., Reference Alomar, Medrano, Cabratosa, Clavero, Lorente, Serra, Monill and Salvador2007). The evaluation of crew members in simulated Mars missions shows that quality of sleep and level of stress induced by extreme conditions may be related to TMD (Bohra et al., Reference Bohra, Bohra and Bohra2019). TMD is a stress-related state related to the deregulation of cortical and melatonin discharge. Simple muscle pain (SM) and TMD were reported in the test groups. A nonsignificant difference was recorded among the TMD and control groups in regard to psychological indications, including depression, obsessive-compulsive disorder, anxiety and somatization. Additionally, daytime dysfunction has been reported to be significantly more common in the TMD and SM groups than in the control group. Considerably lower sleep durations were also observed in the SM group than in the TMD group (Bohra et al., Reference Bohra, Bohra and Bohra2019). In the examination, more significant levels of psychological suffering in most psychological domains were found in people with temporomandibular joint pain. The findings of the studies have shown various degrees of psychological suffering in individuals with TMJ pain compared with the effects of muscle pain in crew members (LeBlanc, Reference LeBlanc1992). The modality of sleep and feelings of anxiety have been related to TMD in investigations and a relationship was found between the pressure scores, salivary cortisol and melatonin levels and the existence or nonexistence of sleep disorders (Bohra et al., Reference Bohra, Bohra and Bohra2019). Enhanced stimulation of the stress hormone axis by cognizant agony discernment is a possible clarification. In any case, the extent of the enhancement could demonstrate that pain in the facial area is a more significant stimulus than pain elsewhere in the body (LeBlanc, Reference LeBlanc1992). TMDs comprise multifactorial aetiologies with a pragmatic relationship with sleep disorders and anxiety because of extraordinary situations within the simulated Mars mission (Rai et al., Reference Rai, Foing and Kaur2012; Rai and Kaur, Reference Rai and Kaur2013a). Investigations have revealed a relationship between sleep disorders and specific types of stress (LeBlanc, Reference LeBlanc1992; Rai et al., Reference Rai, Foing and Kaur2012). Sleep disorders enhance the measure of common indicators of stress and other factors, including salivary cortisol, melatonin and heart rate, which aggravate the impacts of stress (LeBlanc, Reference LeBlanc1992; Paloski et al., Reference Paloski, Black, Reschke, Calkins and Shupert1993; Rai et al., Reference Rai, Foing and Kaur2012). It has been reported that an increased cortisol awakening reaction is related to an enhanced degree of stress (LeBlanc, Reference LeBlanc1992; Rai et al., Reference Rai, Foing and Kaur2012).

This information increases the probability that objective factors thought to drive primary sleep disorders, such as psychophysiological stimulation, as well as improvement in sleep duration and melatonin regulation, may improve the medications for TMD and other idiopathic pain issues, conceivably resulting in prophylactic advantages. Melatonin treatment may help in easing sleep, stress and TMD issues on earth, in space and in extreme situations. However, the existence or nonexistence and level of TMD have not yet been confirmed and the kind of TMD has not been identified in investigations (Bohra et al., Reference Bohra, Bohra and Bohra2019).