Dental anxiety, pain and mindfulness in patients undergoing dental procedures

Maria Antónia Pereira de Barros Dental anxiety, pain and mindfulness in patients undergoing dental proceduresUniversidade do MinhoEscola de MedicinaJulho de 2021 Maria Antónia Pereira de Barros Dental anxiety, pain and mindfulness in patients undergoing dental proceduresMinho | 2021U Maria Antónia Pereira de Barros Dental anxiety, pain and mindfulness in patients undergoing dental proceduresJulho de 2021 Dissertação de Mestrado Mestrado em Ciências da Saúde Trabalho efetuado sob a orientação daProfessora Doutora Patrícia Ribeiro Pinto Universidade do MinhoEscola de Medicina ii DIREITOS DE AUTOR E CONDIÇÕES DE UTILIZAÇÃO DO TRABALHO POR TERCEIROS Este é um trabalho académico que pode ser utilizado por terceiros desde que respeitadas as regras e boas práticas internacionalmente aceites, no que concerne aos direitos de autor e direitos conexos. Assim, o presente trabalho pode ser utilizado nos termos previstos na licença abaixo indicada. Caso o utilizador necessite de permissão para poder fazer um uso do trabalho em condições não previstas no licenciamento indicado, deverá contactar o autor, através do RepositóriUM da Universidade do Minho. Licença concedida aos utilizadores deste trabalho Atribuição-NãoComercial-SemDerivações CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/ iii AGRADECIMENTOS Esta foi uma longa e desafiante jornada, que nunca teria conseguido trilhar sozinha. Quero agradecer em primeiro lugar, à orientadora Professora Doutora Patrícia Ribeiro Pinto por ter aceite este desafio. Agradeço também à Dra. Ana Cristina Paredes, que embora não seja orientadora oficial desta dissertação, teve um papel essencial para a sua concretização. Obrigada às duas pelo conhecimento transmitido, pelo imenso empenho, por todas as horas que dedicaram a este trabalho e por me ajudarem a levar “este barco” a bom porto. Um agradecimento muito especial às colegas Dra. Marta Veiga, Dra. Ana Filipa Terroso, Dra. Carla Casais e Dra. Ilídia Rodrigues, que gentilmente participaram neste projeto e pela amizade de tantos anos. Agradeço também à assistente Andreia por toda a paciência e disponibilidade. A todos os pacientes que amavelmente responderam aos questionários e que comigo partilharam um pouco das suas vidas enquanto aguardavam a consulta. Agradeço ainda aos professores da Escola de Medicina e aos colegas de mestrado. À Raquel, Daniela, Maria João e Carolina, pela amizade, energia positiva e boa disposição. Um agradecimento sentido ao Tiago, companheiro de vida, por ser o meu confidente e melhor amigo. Pela imensa paciência, por todo o apoio e força (mesmo que à distância) e por ser o meu consultor de inglês particular. Por fim, um muito obrigado aos meus pais e mana Luísa. Sem vocês teria sido impossível concretizar este objetivo. Obrigada por todo o apoio, encorajamento e por estarem lá sempre que precisei. Por todas as horas de babysitting a cuidar do neto/sobrinho Duarte, enquanto eu me dedicava à recolha de dados e posteriormente à parte escrita da dissertação. É mais uma dívida que não tenho como vos pagar. A todos vocês, dedico este trabalho e tudo o que ele envolveu. O trabalho apresentado nesta dissertação de mestrado foi realizado no Instituto de Investigação em Ciências da Vida e Saúde (ICVS), Universidade do Minho. O apoio financeiro foi fornecido pelo projeto NORTE-01-0145-FEDER-000039, apoiados pelo Programa Operacional Regional do Norte, Portugal (NORTE 2020), no âmbito do Acordo de Parceria PORTUGAL 2020, através do Fundo Europeu de Desenvolvimento Regional (FEDER) e de fundos nacionais, pela Fundação para a Ciência e a Tecnologia (FCT) – projeto UIDB/50026/2020 e UIDP/50026/2020. iv STATEMENT OF INTEGRITY I hereby declare having conducted this academic work with integrity. I confirm that I have not used plagiarism or any form of undue use of information or falsification of results along the process leading to its elaboration. I further declare that I have fully acknowledged the Code of Ethical Conduct of the University of Minho. v Ansiedade dentária, dor e mindfulness em pacientes submetidos a procedimentos dentários RESUMO A dor e a ansiedade são experiências comuns no consultório médico-dentário que podem resultar no evitamento dos cuidados de saúde oral. A ansiedade dentária é um tipo de apreensão associada com a odontologia. É caracterizada por uma resposta física e/ou emocional a tais estímulos, e tem sido associada a níveis mais elevados de dor e ansiedade durante as consultas. O mindfulness é um processo de atenção sustentada e consciente para as experiências do momento presente, com uma atitude de não julgamento e aceitação, o que pode contribuir para reduzir a dor e a ansiedade em diferentes contextos. No entanto, pouco se sabe sobre a possível influência deste construto no contexto dentário. O objetivo deste estudo foi investigar a associação entre ansiedade dentária, dor e mindfulness, e ainda explorar os preditores de dor/desconforto e ansiedade em pacientes submetidos a procedimentos dentários. Este foi um estudo observacional e exploratório, realizado com 111 pacientes adultos, avaliados antes (T0) e após (T1) uma consulta dentária. Em T0, foram avaliadas medidas sociodemográficas e clínicas, bem como a ansiedade dentária ( Dental Fear Survey ), mindfulness (Escala de Atenção Plena e Consciência), sintomas gerais de ansiedade e depressão ( Patient Reported Outcomes Measurement Information System , versões abreviadas), catastrofização da dor (Questionário de Estratégias de Coping - revisto), ansiedade pré-procedimento (Escala de Classificação Numérica - NRS ) e dor esperada ( NRS ). Em T1, os pacientes reportaram os níveis de dor, desconforto e ansiedade ( NRS ) experimentados durante o procedimento e o dentista preencheu um relatório clínico sobre o tratamento. Os resultados mostraram que a ansiedade dentária estava associada aos níveis de mindfulness (r=-.363, p<.001), sintomas de ansiedade e depressão (r=.304, p=.001 e rsp=.236, p=.013, respetivamente), catastrofização da dor (r=.677, p<.001), ansiedade pré-procedimento (r=.574, p<.001) e dor esperada (r=.449, p<.001). Os modelos de regressão linear hierárquica revelaram que os preditores significativos de dor/desconforto durante o procedimento dentário foram queixa prévia de dor na cavidade oral (ß=.253, p=.001), dor esperada (ß=.458, p<.001) e ansiedade dentária (ß=.197, p=.015). A ansiedade dentária (ß=.288, p<.001), a ansiedade pré-procedimento (ß=.639, p<.001) e a idade (ß=-.113, p=.045) surgiram como preditores significativos de ansiedade durante o procedimento. Globalmente, este estudo revelou a influência significativa de fatores psicológicos na predição de dor/desconforto e ansiedade durante a consulta dentária. Estes resultados podem ser úteis no desenho de intervenções para a gestão da dor, desconforto e ansiedade no contexto odontológico, de forma a promover a adesão aos tratamentos dentários e melhorar a saúde oral da população. Palavras-chave: Ansiedade dentária, Dor, Mindfulness, Predição, Saúde oral vi Dental anxiety, pain and mindfulness in patients undergoing dental procedures ABSTRACT Pain and anxiety are common experiences in the dental office that can result in avoidance of oral health care. Dental anxiety is a kind of apprehension experienced in association with dentistry. It is characterized by a physical and/or emotional response to such stimuli and has been associated with higher levels of pain and anxiety during the appointments. Mindfulness is a process of sustained attention and awareness to the experiences occurring in the present moment, with an attitude of nonjudgment and acceptance, which can contribute to reduce pain and anxiety in different contexts. However, little is known about a possible influence of this construct in the dental context. The aim of this study was to investigate the association between dental anxiety, pain and mindfulness and further explore predictors of pain/discomfort and anxiety in patients undergoing dental procedures. This was an observational and exploratory study, conducted among 111 adult patients, evaluated before (T0) and after (T1) an appointment. At T0, sociodemographic and clinical measures were assessed, as well as dental anxiety (Dental Fear Survey), mindfulness (Mindful Attention Awareness Scale), general anxiety and depression symptoms (Patient Reported Outcomes Measurement Information System short forms), pain catastrophizing (Coping Strategies Questionnaire - revised), pre-procedural anxiety (Numeric Rating Scale - NRS) and expected pain (NRS). At T1, the patients reported pain, discomfort and anxiety levels (NRS) experienced during the procedure and the dentist filled a clinical report about the treatment performed. The results showed that dental anxiety was associated with mindfulness (r=-.363, p<.001), anxiety and depression symptoms (r=.304, p=.001 and rsp=.236, p=.013, respectively) pain catastrophizing (r=.677, p<.001), pre-procedural anxiety (r=.574, p<.001) and expected pain (r=.449, p<.001). Linear hierarchical regression models revealed that the significant predictors of pain/discomfort during the dental procedure were previous oral pain complaint (ß =.253, p=.001), expected pain (ß=.458, p<.001) and dental anxiety (ß=.197, p=.015). Dental anxiety (ß=.288, p<.001), pre-procedural anxiety (ß=.639, p<.001) and age (ß=-.113, p=.045) emerged as the significant predictors of anxiety during the procedure. Globally, this study revealed the significant influence of psychological factors in the prediction of pain/discomfort and anxiety during dental appointment. These findings could be useful for the design of interventions targeting pain, discomfort and anxiety management in dental context, and ultimately promote patients’ adherence to dental care and improve general oral health of the population. Key-words: Dental anxiety, Mindfulness, Oral health, Pain, Prediction vii INDEX DECLARAÇÃO DIREITOS DE AUTOR ............................................................................................................................. ii AGRADECIMENTOS ................................................................................................................................................... iii STATEMENT OF INTEGRITY ....................................................................................................................................... iv RESUMO ................................................................................................................................................................... v ABSTRACT ................................................................................................................................................................ vi INDEX ...................................................................................................................................................................... vii LIST OF ABBREVIATIONS ............................................................................................................................................ ix LIST OF FIGURES ....................................................................................................................................................... ix LIST OF TABLES ........................................................................................................................................................ x INTRODUCTION ......................................................................................................................................................... 1 1. ANXIETY AND FEAR ........................................................................................................................................................ 1 2. DENTAL ANXIETY .......................................................................................................................................................... 2 2.1 CONCEPTUALIZATION ....................................................................................................................................... 2 2.2 PREVALENCE ..................................................................................................................................................... 2 2.3 AETIOLOGY ........................................................................................................................................................ 3 2.3.1 EXOGENOUS FACTORS ............................................................................................................................. 3 2.3.2 ENDOGENOUS FACTORS .......................................................................................................................... 4 2.4 CONSEQUENCES AND IMPACT ........................................................................................................................... 4 2.5 MANAGEMENT STRATEGIES ................................................................................................................................ 6 3. PAIN ........................................................................................................................................................................ 6 3.1 CONCEPTUALIZATION ....................................................................................................................................... 6 3.2 PAIN THEORIES - A BRIEF OVERVIEW ................................................................................................................ 6 3.3 DENTAL PAIN .................................................................................................................................................... 9 3.3.1 PREVALENCE ............................................................................................................................................ 9 3.3.2 STRUCTURES AND MECHANISMS INVOLVED IN DENTAL PAIN ............................................................... 10 3.3.3 ASSOCIATED FACTORS ........................................................................................................................... 11 3.4 PAIN CATASTROPHIZING ................................................................................................................................... 12 3.5 DISCOMFORT ................................................................................................................................................... 13 4. MINDFULNESS ........................................................................................................................................................... 14 4.1 CONCEPTUALIZATION ..................................................................................................................................... 14 4.2 MINDFULNESS-BASED PROGRAMS (MBP) ....................................................................................................... 14 4.3 HEALTH BENEFITS ........................................................................................................................................... 15 4 The indirect pathway includes vicarious learning (modelling) or exposure to threatening information. Vicarious learning is based on social learning theory and proposes that anxiety can develop during childhood as a result of the child observing the anxious behaviour of another person, generally the mother, and imitating that behaviour (2). Dental anxiety may also develop as a result of direct exposure to negative information about dental procedures. According to this pathway, children will learn to be fearful as a result of the negative information they have seen or heard from family members, peers or media (2). 2.3.2 Endogenous factors An alternative explanation to the development of dental anxiety is that some individuals may be particularly vulnerable to feelings of anxiety. Endogenous factors which may increase the susceptibility to dental anxiety include gender, age, psychological characteristics and eventually genetic vulnerability (2,3). Two trends revealed in research are that females have increased levels of dental anxiety when compared to males (2,14) and that younger individuals usually report higher levels of dental anxiety than older individuals (20,21). Additionally, several psychological characteristics (such as low selfesteem, general fearfulness, alcohol dependence), together with psychiatric diagnoses ( e.g. conduct disorder, agoraphobia, simple phobia, etc.) are more frequent in patients with high dental anxiety (3). Regarding the heritability of dental anxiety, little is known, but a genetic predisposition for its development has been suggested (2,14,16). 2.4 Consequences and impact Dental anxiety may result in the avoidance of dental care and in subsequent oral health deterioration, which is likely to have a detrimental impact in quality of life (15,16). As oral health deteriorates, pain symptoms may appear, which can have a negative interference in daily activities, disturbing sleep, decreasing vitality and culminating in withdrawal from school or work activities. In addition to pain, patients presenting dental anxiety have a higher probability of developing aesthetic flaws caused by tooth decay, fractures or parafunctional habits ( e.g. bruxism, fingernail biting, etc.) (15,22). In a society where healthy teeth are among the accepted norms, an unsatisfactory dental appearance may negatively affect social relationships, with negative psychological impact as well as lower self-confidence and self-esteem (10,15,22,23). 5 Additionally, a vicious cycle of anxiety and avoidance has been proposed, whereby feeling anxious about attending the dentist can result in nonattendance of regular appointments, with a subsequent greater need for more extensive, complex and expensive treatments, and consequently greater avoidance of dental situations (10,11,15,19,22). Figure 1 illustrates this negative cyclical pattern of dental anxiety. Figure 1. Negative cyclical pattern of dental anxiety [adapted from Daniel et al. (2008) (24)] From the perspective of the dentist, treating patients with dental anxiety may cause irritation, anger and frustration, and may negatively affect the performance of the dental practitioner due to the stress experienced. The treatment of these patients is often considered time-consuming and economically unprofitable (16,25). Patients suffering from dental anxiety tend to have more appointment cancellations or fail to attend completely, together with a heightened perception of pain (26). Moreover, these patients usually have longer recovery periods and higher analgesic consumption after dental invasive treatments (25). There is also a well-documented association between oral health and the development and/or severity of certain systemic diseases or disorders, reinforcing the importance of adequate dental care (27). Several studies have linked poor oral health with cardiovascular disease, poor glycaemic control in diabetics, low birth weight pre-term babies, respiratory diseases and a few other conditions, including rheumatoid arthritis and osteoporosis (27–30). The infection and inflammation that occurs in oral/periodontal environment is a risk factor for these systemic diseases. These associations are biologically plausible due to the potential direct effects of oral Dental anxiety Avoidance of dental treatment Poor oral health Negative oral health experiences/more complex treatment 6 microorganisms ( e.g. lipopolysaccharides ) on distant tissues and organs, as well as the systemic effects of inflammatory mediators, produced in the periodontal tissues (27,29). 2.5 Management strategies Modern dentistry has undergone a major evolution in the last century, with great advances in biotechnology procedures, upgrades in patient comfort, as well as the available pharmacology (3,25). Considering dental anxiety, some strategies have been used to manage this condition, such as pharmacological approaches ( e.g. benzodiazepines and nitrous oxide), careful explanation of the treatment procedure, biofeedback, hypnosis, guided imagery, aromatherapy, acupuncture, behavioural interventions and relaxation approaches (1,3,10,18,25). Mindfulness-based approaches may also be potentially useful strategies (31). 3. Pain 3.1 Conceptualization Similarly to anxiety, pain has a primary role in survival, acting as an alarm system or a warning device, activated in face of real or potential damage. It enables the organism to avoid possible harm and to ensure that body healing occurs (32,33). Over the years, the pain definition proposed by the International Association for the Study of Pain (IASP) has been a target of criticism and discussion in the pain field, with several alternatives being proposed (34). As a result, the definition of pain has been recently revised to “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage” (35). Pain is always a subjective experience, and it can be reported even in the absence of tissue damage or any likely pathophysiological cause (36). In a more simplistic way, “pain is what the individual says it is” (37). 3.2 Pain theories – a brief overview Throughout the history of humanity, some theories have been proposed to explain why and how individuals feel pain. Early pain theories conceptualized pain as a unidimensional phenomenon, resulting directly from a physical stimulus in the realm of the biomedical model. This perspective only focused on biological variables and did not acknowledge other influences on pain perception, such as emotions or cognitions (38). Pain was considered as a mere result of nociception (39). 7 Nociception is the process that comprehends the initial physical stimulus causing body damage and the subsequent neurobiological chain of reactions. It is a non-conscious process (39), consisting in the physiological detection of tissue damage through the activation of specialized sensory receptors, called nociceptors, attached to A delta (Aδ) and C fibres (40). Pain, in its turn, is a conscious phenomenon, not only a primitive sensory message of tissue trauma, but rather a complex psychological experience (41). This is in accordance with the gate control theory of pain (42), which questioned the direct and causal relationship between stimulus intensity and pain perception. It was the first theory conceiving pain through a mind-body perspective and as a multidimensional experience, suggesting that both physiological and psychological variables accounted for pain experience (42). Overall, it advanced with the premise that pain is modulated at the level of the spinal cord by both peripheral and central nervous system inputs. Accordingly, the theory proposes the existence of a mechanism in the dorsal horn of the spinal cord, acting as a “gate”, which modulates the transmission of pain-related nerve impulses, opening or closing according to the type of stimuli arriving. This mechanism is influenced by the balance between small-diameter and large-diameter non-nociceptive nerve fibers activity. While small-diameter fibers facilitates pain transmission, opening the gate, large-diameter fibers inhibits pain transmission, closing the gate. Hence, the activation of these latter fibers, due to stimuli such as rubbing the skin, can inhibit pain that arises from the activation of nociceptive fibers. In this case, the gate closes, and the brain does not receive the nociceptive information that is coming from the periphery. Contrarily, when the gate opens, the nociceptive stimuli can travel to the brain where it is processed, and as a result the individual experiences pain (42) (Figure 2). Besides the influence of the gate at the peripheral afferent nerve activity level, the authors also proposed that processes in the brain modulate the gating mechanism, suggesting a descendent modulatory system. In this line, central pathways, descending from the brain, have the potential of opening or closing the gate, modulating the transmission of nociceptive information at spinal cord level and thus facilitating or inhibiting pain perception (43,44). Psychological processes, such as attention, beliefs, expectations and mood would exert an influence on pain perception at this level (42). For example, while attention directed toward pain opens the gate, attention directed away from pain closes it. Thus, by emphasizing the modulation of inputs at the spinal dorsal horns level by the dynamic role of the brain in pain process, this theory was the first one acknowledging the integration of psychological factors into pain experience (45). Later, in 1968, Melzack and Casey further extended the model in order to better integrate the affective, motivational and cognitive 8 aspects of pain. They posed that pain results from a complex and dynamic interaction among three dimensions: a sensory-discriminative dimension, a cognitive-evaluative dimension and an emotional-motivational dimension, each of one having a reciprocal influence on the others. The gate-control model transformed the conceptualization and understanding of pain, by recognizing and explaining that pain is influenced by multiple factors, therefore expanding the range of potential interventions aimed at pain prevention and control (46). Figure 2. The gate control theory of pain [adapted from Cho and Min, 2015 (47)] Another relevant theory to understand pain is the biopsychosocial model, which also conceptualizes pain as a multidimensional experience. This theory postulates that pain results from a complex interaction among biological, psychological and social factors, which affect the individual’s physical and mental well-being. George Engel (1977) claimed that the approach of a disease must consider its multidimensional nature and regard the patient as a whole instead of focusing on a single dimension (48). The interaction of psychosocial factors, such as personality, stressful events and social context, with genetic and biological characteristics, influences the severity and course of diseases (49). Following Engels work, Loeser (1982) added to the biopsychosocial model of pain, suggesting that four elements need to be taken into consideration and distinguished when evaluating a patient with pain. These elements include nociception, pain, suffering and pain behaviours. Nociception, as mentioned above, corresponds to the signal that is sent to the brain from the periphery to alert the body that there is some degree of injury or tissue damage. Pain, on 9 the other hand, is the subjective experience that occurs after the brain has processed the nociceptive input. Regarding the last two components, suffering is the individual emotional response triggered by the experience of pain and pain behaviours are the actions that people carry out in response to experiencing pain. These two components can be either conscious or subconscious (48). 3.3 Dental pain Pain is a common experience for patients undergoing dental treatments. Dental pain is characterized as pain originating in the teeth and supporting tissues as a result of disease or injury (50,51). It is frequently subsumed under the broad term of "orofacial pain" (50), that in turn comprises multiple painful conditions affecting the oral, head, face and neck area (52). Several oral clinical conditions are associated with reports of dental pain, such as dental caries or tooth decay, infected pulpal tissue, abscesses, oral ulceration, trauma, among others (53,54). Dental pain is the most common symptom that compels patients to seek dental treatment and it has physical, psychological and emotional consequences to patients (51,55). Studies have shown that school/job absenteeism, sleep disturbances, difficulty in chewing and difficulty in socialization are events commonly associated with dental pain, which may negatively affect patient’s well-being and daily life (50,51). 3.3.1 Prevalence A review of 23 studies published in Medline from 1966 to 2001 found a prevalence of dental pain ranging from 7 to 66% (51). This variation may be explained by the use of different definitions for dental pain as well different sample dimensions and selection ( e.g. community dwelling adults, patients attending dental practices, factory workers, armed forces, etc). Additionally, this review showed that younger patients and those from lower socio-economic groups were more likely to report pain (51). Two subsequent empirical studies reported a prevalence of dental pain of 43% among working population (56) and of 77.6% among adults with severe dental anxiety (50). Regarding the Portuguese population, a study with a sample of 1102 individuals, over 15 years of age, aiming to characterise oral-health status, habits and perceptions, found that 69.3% had experienced toothache or gingival pain at least once in their life (57). 10 3.3.2 Structures and mechanisms involved in dental pain Dental pain is caused by noxious stimuli that may cause an insult of the dental pulp. Some examples are bacterial infections, chemical or mechanical erosion of enamel, or recession of gingiva (58,59). The dental pulp resides in a rigid compartment consisting of dentin and enamel, which provides a support structure and protects it from the microbes present in the mouth (59). When that protective chamber is damaged, exposing the dentinal tubules, the pulp becomes susceptible to the hostile elements present in the oral cavity. An inflammation of the pulp, or pulpitis, may occur, which is characterized by increasingly intense and prolonged painful responses to thermal or osmotic stimulation. In an early stage, the inflammatory responses may be reversible, but as the pathology advances, the process becomes irreversible, and may result in the development of spontaneous pain. When left untreated, infection and inflammation progress, eventually leading to pulpal necrosis and periapical pathology (59). Caries removal and filling therapy are adequate procedures during reversible pulpitis. However, endodontic therapy is necessary when pulpitis has reached an irreversible stage (60). Figure 3 illustrates the anatomy of the dentin-pulp complex. Figure 3. Dentin-pulp complex anatomy Figure 4. Intradental innervation Figure 3. Illustration of the anatomy of the dentin-pulp complex [adapted from Närhi et al. (2016) (60)] Figure 4. Illustration of the distribution of intradental Aand C-fibers [adapted from Närhi et al. (2016) (60)] Dentinal tubules 11 According to the hydrodynamic theory, movement of fluid within the dentinal tubules induces pain via nociceptive fibers located around the odontoblast process and at the dentin-pulp border (60). Both trigeminal nerve and trigeminal nucleus caudalis play an important role in processing the orofacial sensory information and may also be involved in dental pain transmission (32). The activation of intradental nerves is able to induce extremely intense pain, which can be explained by the dense and predominantly nociceptive innervation of the dental pulp. Each tooth is innervated by about a thousand trigeminal axons and approximately 20 000 – 30 000 nociceptive nerve endings/mm2 are found in the dentin-pulp border (60). The nerve supply of the dentin-pulp complex is mainly made up of mechanosensitive nociceptors, namely A fibers (both δ and ) and C fibers. Figure 4 illustrates the intradental innervation. The A-δ fibers transmit nociceptive stimuli directly to the thalamus inducing a sharp pain that can be easily localized. The C fibers are influenced by many modulating interneurons before reaching the thalamus thus resulting in a slow pain, which is generally characterized as dull and aching (58). A-fibers react to cold or mechanical stimuli, such as cold drinks or toothbrushing, while Cfibers are mainly activated by inflammatory mediators (60). In addition, nerve fibers release neuropeptides, such as calcitonin gene-related peptide, substance P, neurokinin A and neuropeptide Y. The increased release of these neuropeptides in the dental pulp causes vasodilation, leading to increased local tissue pressure and capillary permeability, causing plasma extravasation and edema formation. Clinically, this can be perceived as throbbing pain, sometimes difficult to localize, making diagnosis a challenging situation for the dentist (60). 3.3.3 Associated factors The sensory reaction to pain is complex and individuals vary widely in their pain sensitivity. Not everyone feels the same pain intensity with the same stimulus (59). The main factors that are thought to influence pain intensity in dental context are previous pain experiences, emotional state and gender (32). First, previous pain experiences may influence pain perception since the repetition of similar circumstances can amplify nociception, such as in face of former traumatic experiences. Another possible explanation is that a patient who had experienced painful dental treatments could feel more pain due to increased sensitization (2,32). Second, the role of emotional state in pain perception can be explained by the activation of the limbic system, within the process of descending modulation (Figure 2). When nociceptive impulses reach the thalamus, they are directed to cortex 12 and limbic structures where pain experience is processed at an emotional level, in which emotions such as fear, rage, sadness or depression can be triggered and affect pain experience (32). Additionally, a positive correlation between stress and the frequency and severity of pain has been reported. Prolonged stressful experiences increase sympathetic nervous system activity even in the absence of the real physical threat. Previous studies have shown that dental anxiety is a significant predictor of expected and experienced pain during oral treatments (26,61,62). Anxiety may lower the pain threshold levels and cause a usually innocuous stimulus to be perceived as painful. Third, according to the results of classical pain studies, women are more likely than men to report more severe pain and for longer duration (32). In turn, men tend to present greater pain thresholds together with higher pain tolerance. It has been proposed that gender effects on pain result from an interaction of biological, psychological, and sociocultural factors (52). For example, males are thought to have been socialized to suppress outward signs of pain (32,63). 3.4 Pain catastrophizing Pain catastrophizing can be defined as an exaggerated negative mental set of cognitions and emotions in response to an actual or anticipated painful experience (64). People who catastrophize have exaggerated negative thoughts when interpreting their pain (65). They are more likely to excessively focus on pain, pain related objects or procedures (rumination), they tend to magnify the threat value of pain (magnification) and they have an inability to successfully cope with pain (helplessness) (66). Pain catastrophizing is associated with higher levels of dental anxiety (10,61,66). Moreover, previous studies suggest that pain catastrophizing is directly associated with increased pain in dental context (64,66,67). In the same line, Lin et al. (2013) demonstrated that participants with higher pain catastrophizing scores reported increased levels of pain and anxiety in an unpredictable and stressful dental context (61). Additionally, the authors found that brain activation at the right posterior hippocampus, a region critically related to associative learning of aversive stimuli and context, was correlated with the individual pain catastrophizing level. The study highlights therefore the role of cognitive-affective factors in pain control of dental patients (61). Another research reported statistically significant differences in pain between patients with high and low pain catastrophizing scores, following the application of orthodontic separators (a dental treatment procedure) (68). Another study (69), among patients who underwent removal of an impacted mandibular third molar, found that postoperative pain and analgesic consumption was higher in 13 patients with higher pain catastrophizing. According to the authors, individuals who catastrophize more have a tendency to exaggerate the sensation of pain and also a lower ability to cope with it, which may adversely affect the dental treatment (69). Besides the direct influence of pain catastrophizing on the experience of pain and anxiety, it also indirectly reinforce avoidance behaviour (66). 3.5 Discomfort Discomfort is a subjective concept, often related to pain (70). Discomfort associated with dental treatment can be defined as a set of emotions felt during the treatment, caused mainly by pain and anxiety. This implies that discomfort is multidimensional, consisting of a combination of behavioural, cognitive and physiological components (71,72). According to Ashkenazy and Ganz (2019), who recently proposed a clarification of the concept, discomfort can be defined as a negative physical and/or emotional state, causing unpleasant feelings or sensations (70). This results in a natural response of avoidance or reduction of its source. It can be divided in two main domains, physical and psychological (70). Physical discomfort is defined as an unpleasant body feeling or sensation, such as fatigue, sleeplessness, shortness of breath, or thirst. Pain is often described as the main source of physical discomfort, but there are other non-pain-related sources, such as adverse environmental conditions, postoperative discomfort or pregnancy (70). Psychological discomfort refers to unpleasant emotions that a person might experience and can lead to feelings such as anxiety, fear, depression, embarrassment, isolation or vulnerability. Researchers have found strong and significant correlations between some of the physical symptoms of discomfort ( e.g. thirst, hunger, and dyspnoea) and anxiety (73). Furthermore, one of the conditions that can accelerate psychological discomfort is physical discomfort (70). In the dental context, there are several moments during the appointment that may cause discomfort to patients. Examples are the discomfort of local anaesthesia injection (74); discomfort during treatment of carious lesions when using rotating instruments, such as burs, as well as during application of the matrix and wedge (72); discomfort during oral surgery procedures (71); or discomfort after placement of orthodontic appliances, which is expressed as feelings of pressure, tension, soreness of teeth and pain (32). 20 AIMS 1. General aim − To investigate the association between dental anxiety, pain and mindfulness and further explore predictors of pain, discomfort and anxiety in patients undergoing dental procedures. 2. Specific aims − Assess the baseline levels of dental anxiety and mindfulness in patients undergoing dental procedures. − Describe the intensity of pain, discomfort and anxiety reported by patients during dental procedures. − Examine the differences on demographic (age, sex), clinical (previous traumatic experience, previous oral pain complaint) and psychological baseline measures, as well as on the outcome measures intensity of pain, discomfort and anxiety, according to the type of dental procedure performed ("Conservative and Prophylactic" versus "Invasive and Urgency"). − Compare the demographic (age, sex), clinical (previous traumatic experience, previous oral pain complaint) and psychological baseline measures, as well as the outcome measures intensity of pain, discomfort and anxiety, according to the level of dental anxiety (low/moderate versus high). − Investigate the predictive value of psychological baseline measures (dental anxiety, mindfulness, general anxiety symptoms, depression symptoms, pain catastrophizing, preprocedural anxiety and expected pain), on the outcome measures pain, discomfort and anxiety. 21 METHODS AND MATERIALS 1. Design This study has an observational and exploratory design with longitudinal assessment at two moments: before and after the dental appointment. Immediately before the dental appointment (T0), participants were assessed in terms of sociodemographic and clinical information, dental anxiety, mindfulness, general anxiety and depression symptoms, pain catastrophizing, preprocedural anxiety and expected pain. Right after the dental appointment (T1), pain, discomfort and anxiety, experienced during the procedure, were assessed and the dentists filled in a clinical report. 2. Participants The study was conducted in three dental clinics: Clínicas Dentárias FA - Carvalhos (Vila Nova de Gaia), Clínica das Granjas (Braga) and Clínica Dentária Medivila (Vila Verde). Recruitment took place between August 2019 and July 2020. No data was collected from the 6th of March to the 17th of May 2020, due to the Covid-19 pandemic and the contingency measures that were in place at that time. The inclusion criteria were: adult female or male individuals attending one of the dental clinics referred above, with ages between 18 to 75 years old. Due to the exploratory nature of this study, all types of dental treatments were included, to analyse potential associations between the outcomes and the procedure type. The exclusion criteria were: individuals that were reporting intense pain that could influence their focus and interfere with the completion of the questionnaires; inability to understand, speak and write Portuguese or to give informed consent to the study; severe and debilitating organic or neurological conditions ( e.g . cancer, dementia); and severe psychiatric conditions ( e.g . schizophrenia). There were no restrictions in recruitment based on pain treatments or other medications ( e.g. antidepressants). Sample size estimations were performed using G*Power V.3.1.9, accounting for a multiple linear regression, medium effect size (f2 = 0.15), significance level (, type I error) of 0.05 and statistical power (1-, type II error) of 0.95. The sample size estimation indicated a total of 146 participants, 22 which was not possible to reach due to the recruitment limitations imposed by the Covid-19 containment measures. After these were lifted, the number of patients attending the clinics decreased and the strict protection rules adopted made it difficult to collect data. Recruitment stopped in July 2020 in order to comply with the planned timeline of this study. This was a convenience sample in which the first 111 participants who met the inclusion criteria and were willing to participate in the study were recruited. From the approached patients (n=118), five denied participating due to dental pain, nervousness and time constraints. Other two patients did not complete the T1 assessment due to lack of time after the end of the dental appointment. The flow diagram of study enrolment is described in figure 5. The statistical power for the final sample (n=111) is 0.86. Figure 5. Flow diagram of the study enrolment Participants approached (n=118) Excluded (n=5) - Dental pain (n=2) - Nervousness (n=1) - Time constraints (n=2) Informed consent and baseline assessment (T0) (n=113) Excluded (n=2) - Time constraints after the dental appointment (n=2) Follow-up (T1) (n=111) 23 3. Procedure Before the study started, the researcher received training to ensure proficiency and uniformity in data collection. All instruments and study procedures were piloted in a sample of 10 patients, to evaluate comprehension and feasibility. For data collection, the patients were approached by the researcher in the waiting room, before the dental appointment, to present the study, invite for participation and clarify possible doubts. After acceptance, patients signed the informed consent and answered the questionnaires (T0). Following the dental appointment, the participants completed T1 assessments, and the dentist filled in the clinical report. 4. Variables and Measures The information was collected using the Portuguese versions of the following questionnaires: 4.1 Baseline Measures (T0) • Dental anxiety was evaluated using The Dental Fear Survey (DFS) (126–128), which has 20 items answered through a 5-point Likert scale (1= “never” or “not at all”, 2= “once or twice” or “a little”, 3= “few times” or “some”, 4= “often” or “great” and 5= “nearly every time” or “very much”). It has three subscales: avoidance of dental treatments, physiological arousal during dental treatments and fearfulness of dental stimuli (126). The score ranges from 20 (lower level of dental anxiety) to 100 (higher level of dental anxiety). A cut-off for high dental anxiety has been suggested at ≥ 60 (1,129). This questionnaire has as target population adult individuals and presents satisfactory data regarding fidelity and validity (127). The Portuguese version of the DFS has good psychometric properties and follows the original factorial structure of 3 factors, with a Cronbach’s alpha () of 0.94 (127). In the current study, internal consistency was very high for the global scale (= 0.97), as well as for the three subscales: avoidance (= 0.94), physiological arousal (= 0.91) and fearfulness of stimuli (= 0.95). • Mindfulness was assessed through The Mindful Attention Awareness Scale (MAAS) (130,131), containing 15 items intended to assess a central feature of trait mindfulness, that is, the general tendency to be aware of the present moment, in the various experiences of daily life (131). In the original version, the items are assessed using a 6-point Likert 24 scale (1= almost always, 2= very frequently, 3= somewhat frequently, 4= somewhat infrequently, 5= very infrequently, 6= almost never) and give rise to a score that can range from 15 to 90, where higher scores reflect greater mindfulness capacity (131). However, in the pilot study, the participants had some difficulty in understanding the Likert scale options, especially when it was necessary to differentiate between the options 3 “somewhat frequently” and 4 “somewhat infrequently”. Therefore, it was decided to change the scale to a 5-point Likert scale (1= almost always, 2= very frequently, 3= frequently, 4= less frequently, 5= almost never). This new answer format was well accepted by the study sample. Another change had to be made, with the item number 12 that asks about mindfulness attitude while driving: “I drive to places on ‘automatic pilot’ and then wonder why I went there.” Some patients that did not drive, could not answer the question properly, so an extra option was added to answer this question: “I don´t drive”. With these two changes, the total score had to be modified and is now given by the sum of the scores obtained in each item (ranging from 15 to 75), divided by the total number of questions items and varies between 1 and 5, where higher scores indicate greater mindfulness skills. The authors of the original version reported strong psychometric properties for this scale and a one-dimensional structure, with internal consistency coefficient (Cronbach’s alpha) of 0.84 (130). The subsequent studies of MAAS confirmed a single factor structure through factor analyses. The Portuguese version reported also a single-factor model, with good psychometric properties, and a Cronbach´s alpha of 0.90 and 0.89 (tested in two different samples) (131). In the current sample, the Cronbach’s alpha coefficient was 0.86, indicating good reliability. • General anxiety and depression symptoms were evaluated through the short form PROMIS 1.0 anxiety and depression questionnaire, translated from the original version of Pilkonis (2011) (132). The PROMIS (Patient Reported Outcomes Measurement Information System) is a National Institute of Health item bank that enables the quantification of symptoms and key health concepts of various chronic diseases. The questionnaires used in this study consist of a total of 4 items each and evaluate symptoms of general anxiety and depression according to a 5-point Likert scale (1= never, 2= almost never, 3= sometimes, 4= almost always and 5= always). Scores range from 4 (lowest possible score) to 20 (highest score), with higher scores indicating more severe symptoms (132). A score 25 of 8 has been proposed as the cut-off for clinically relevant symptoms in both scales (133). In the current sample, internal consistency was adequate for both anxiety (= 0.82) and depression (= 0.91). • Pain catastrophizing was assessed using the pain catastrophizing subscale from the Coping Strategies Questionnaire – revised form (134), which has 6 items, classified on a 5-point Likert scale (1= never, 2= almost never, 3= sometimes, 4= almost always and 5= always). The total score is given by the sum of the scores obtained in each item and varies between 6 and 30, with higher scores revealing a greater trend to catastrophize (135). In this study, the internal consistency for the pain catastrophizing subscale scores was high (= 0.89). • Pre-procedural anxiety was evaluated through a Numeric Anxiety Rating Scale (NARS), from 0 to 10, with the value "0" corresponding to the absence of anxiety and the value "10" corresponding to the worst possible anxiety. • Expected pain was assessed by a Numeric Pain Rating Scale (NPRS) from 0 to 10, with the value "0" meaning the absence of pain and the value "10" indicating the worst possible pain. 4.2 Outcome Measures (T1) • Pain during the dental procedure was assessed by the NPRS described above. • Discomfort associated with the dental procedure was assessed by the Numeric Discomfort Rating Scale (NDRS), analogous to the NPRS, from 0 to 10. The value "0" corresponds to the absence of discomfort and the value "10" corresponds to the worst possible discomfort. • Anxiety during the dental procedure was evaluated through the NARS described for T0 assessment of pre-procedural anxiety. For all the Numeric Rating Scales (NRS) mentioned above, the values between "1-3" correspond to mild pain, discomfort or anxiety, those between "4-6" correspond to moderate pain, discomfort or anxiety and finally those between "7-10" reflect severe pain, discomfort or anxiety. 26 Participants were also asked to fill in a sociodemographic and clinical questionnaire, to collect data regarding age, sex, marital status, level of education, profession and professional status, among other information. Additionally, the presence or absence of oral pain complaint before the appointment, the existence of a previous traumatic experience during a dental appointment, as well as first-time attendance, were also registered. The dentists completed a clinical report with relevant information regarding the treatment performed, such as the reason for the appointment (routine or emergency), type of treatment, duration of the appointment, and type and dose of local anaesthesia, if administered. The type of treatment was classified, a posteriori, in two categories "Conservative and Prophylactic" (oral examination, scaling, dental restoration, orthodontics, fixed or removable prosthesis) or "Invasive and Emergency" (simple or surgical tooth extraction, endodontic treatment, implant placement, urgency-resolution painful situation). When more than one treatment was performed, only the most invasive one was considered (127). 5. Statistical analysis Data was analysed using IBM Statistical Package for the Social Sciences version 25 (IBM © SPSS Statistics; Chicago, IL, USA). Internal consistency of responses to the questionnaires was assessed using Cronbach’s alpha (136). For self-report instruments, the scales or subscales were only considered acceptable if alpha coefficients were above 0.70 (137). All variables were tested for normality using Kolmogorov–Smirnov and Shapiro-Wilk tests. When the results of these tests were statistically significant (p< 0.05, suggesting non-normality of distribution), the absolute skewness and kurtosis values were analysed. Values below 2.0 and 7.0, respectively, indicate small departures from normality and, in these cases, the indication to proceed with parametric statistics was followed (138). No significant violation of normality was observed, except for the variable depression (PROMIS) (skewness = 2.303). Descriptive statistics were computed on sample characteristics. These are expressed as absolute and relative frequencies (n, %) for categorical data. To provide a thorough account of continuous variables, these are described as mean (M), standard deviation (SD), median (Md), minimum and maximum values (Min-Max). 27 A new composite dependent variable “pain/discomfort” was created by computing the mean value of the variables pain and discomfort during dental treatment. This decision was based on the fact that the participants were not always able to discriminate between these two concepts. This new variable was used in the remaining statistical analyses. Fisher´s exact tests and Mann-Whitney tests (for categorical and continuous variables, respectively) were performed to analyse differences between groups: type of dental procedure performed (conservative and prophylactic versus invasive and emergency) and dental anxiety level [low/moderate (DFS < 60) versus high (DFS ≥ 60)]. Fisher´s exact tests was used due to the fact that more than 20% of cells had expected frequency of less than five (139). Mann-Whitney nonparametric test was used due to largely different sample sizes in each group (140). To determine the meaningfulness of the differences (practical significance), since statistical significance (p-value) is dependent on group size, the associated effect sizes (ES) were also computed. They were expressed as Phi (φ) for categorical variables and r score (r= Z/√n) for continuous variables. Cohen’s guidelines for r score are that a large effect is above 0.5, a medium effect is above 0.3, and a small effect is above 0.1 (141). The same guidelines are applied for Phi (φ) effect size of 1 degree of freedom (142). In addition, Pearson’s and point-biserial correlation coefficients were computed to determine the strength of relationships between variables and to select the set of demographic (age and sex), clinical (previous traumatic experience, previous oral pain complaint and anaesthesia) and psychological (dental anxiety, mindfulness, general anxiety symptoms, depression symptoms, pain catastrophizing, pre-procedural anxiety and expected pain) predictors to include in the regression models, based on the presence of a significant correlation with the dependent variables. Due to non-normality of distribution, Spearman correlation was computed for the variable depression. Multiple linear hierarchical regression models were used to find associations between the psychological baseline measures (dental anxiety, mindfulness, general anxiety and depression symptoms, pain catastrophizing, pre-procedural anxiety and expected pain) and the outcome measures pain/discomfort and anxiety reported during the dental treatment. For each regression model, a maximum of 7 variables were selected, based on the principle of 15 participants per independent variable (143). The influence of age and sex was controlled in the first block of each model irrespectively of their statistical significance. The second block included relevant clinical variables that presented a significant correlation with each outcome. The third block included the psychological variables that showed a significant association with the outcome 28 variables. In case of a strong correlation between independent variables (r≥ 0.7) (144), only the variable with the strongest correlation with the outcome was selected. For the regression model to be valid, the assumptions of normal distribution of the residuals, homoscedasticity, linearity and multicollinearity were checked (145). Additionally, the presence of outliers was identified through visual inspection of histograms and frequency distributions (146), and by looking at the standardised residual, making sure that the minimum and maximum values do not exceed ± 3 (147). Statistical significance for all tests was set at p< 0.05. 6. Ethical Considerations Ethical approval for this study was granted by the Life Sciences and Health Ethics Subcommittee (University of Minho) (CEICVS 024/2019). Also, the clinic directors of the clinics involved in the research authorized the recruitment of patients in their clinics. All procedures were conducted following the guidelines and good ethical research practices, in order to fulfil the precepts of the Declaration of Helsinki and the Convention on Human Rights and Biomedicine. Before data collection, the study was explained to all participants and the written informed consent was obtained. The study was conducted ensuring the anonymity and confidentiality of the participants. Furthermore, participation was entirely voluntary, with participants being free to refuse or abandon the study at any time. The involvement in the study did not interfere with dental treatment and did not interfere with physical and/or psychological integrity. 29 RESULTS 1. Sociodemographic, clinical and dental appointment characteristics Sociodemographic and clinical characteristics for the total sample (N=111) are presented in Table 1. The sample mean age was 38.83 years (SD=13.92). It included 73 (65.8%) women and 38 (34.2%) men. Half of the patients were married/cohabiting (56, 50.5%). The majority of the patients had a college or postgraduate education (73, 65.8%) and were employed (80, 72.1%). Regarding clinical indicators (Table 1), 23 (20.7%) participants suffered from a chronic disease. High blood pressure, asthma and depression were the most commonly reported. The same number of patients (23, 20.7%) reported taking medication daily. With respect to variables related to dental appointment (Table 2), 26 (23.4%) patients stated having experienced a previous traumatic experience during a dental appointment. The majority of the participants visited the dentist every 6 months (46, 41.4%) or once a year (35, 31.5%) and 15 (13.5%) participants went to the dentist just in emergency situations (pain/other problems). One patient took an anxiolytic medication before the appointment. The type of treatment administered was most frequently conservative or prophylactic (97, 87.4%), often planned as a routine procedure (101, 91.0%). The majority of the participants did not present any oral pain complaint pre-treatment (90, 81.9%) and 9 (8.1%) participants were meeting that dentist for the first time. Most of the dental procedures took less than 30 minutes (63, 56.8%) or 30 to 60 minutes (43, 38.7%), often without anaesthesia (67, 60.4%). Table 1. Sociodemographic and clinical characteristics of study participants (N=111) Sociodemographic characteristics n (%) Age (years) M=38.83, SD=13.92 Md=37.00, Min-Max=18 - 74 Sex Female Male 73 (65.8%) 38 (34.2%) Marital status Single Married/cohabiting Separated/divorced 45 (40.5%) 56 (50.5%) 10 (9.0%) 36 NOTE: Continuous variables are presented as Mean Rank; Categorical variables are presented as n (%); sex, 0= men and 1= women; previous traumatic experience, 0= no and 1= yes; previous oral pain complaint, 0= no and 1= yes; Abbreviations: df, degrees of freedom; DFS, Dental Fear Survey; MAAS, Mindful Attention Awareness Scale; PROMIS, Patient-Reported Outcomes Measurement Information System; CSQ-R, Coping Strategies Questionnaire – revised form; NARS, Numeric Anxiety Rating Scale; NPRS, Numeric Pain Rating Scale; NRS, Numeric Rating Scale. 4. Differences on baseline demographic, clinical and psychological measures, and on pain/discomfort and anxiety levels during the dental procedure, according to the level of dental anxiety Patients were compared according to the level of dental anxiety: low or moderate dental anxiety (DFS < 60) and high dental anxiety (DFS ≥ 60) (1,129) (Table 5). Patients with high dental anxiety presented statistically significant lower levels of mindfulness with a small ES (U=354.00, p=.004, r=-.27), than those with low or moderate dental anxiety. Moreover, high dental anxious patients presented higher levels of pain catastrophizing (large ES) (U=95.50, p<.001, r=-.50), pre-procedural anxiety (medium ES) (U=296.50, p<.001, r=-.33) and expected pain (medium ES) (U=329.00, p=.002, r=-.30), as well as pain/discomfort (small ES) (U=431.50, p=.027, r=-.21) and anxiety (medium ES) (U=278.50, p<.001, r=-.35), than those with low or moderate dental anxiety. Looking at the demographic and clinical variables, only age (small ES) (U=434.50, p=.030, r=-.21) and the presence of previous traumatic dental experience (medium ES) (χ2(1)=21.363, p=<.001, r=.453) provided statistically significant results. Table 5. Differences on baseline demographic, clinical and psychological measures, and on pain/discomfort and anxiety levels during the dental procedure, according to the level of dental anxiety (Fisher’s exact test and Mann-Whitney test) Dental Anxiety Low/Moderate (n=97) High (n=14) U/ χ2 (df) p - value Effect size r / φ Baseline measures (T0): Before dental procedure Age 53.48 73.46 434.50 .030 -.21 Sex (woman) 63 (64.9%) 10 (71.4%) .228 (1) .768 .045 Previous traumatic experience (yes) 16 (17.6%) 10 (76.9%) 21.363 (1) <.001 .453 37 Previous oral pain complaint (yes) 17 (17.5%) 4 (28.6%) .973 (1) .299 .094 Mindfulness (MAAS) 59.35 32.79 354.00 .004 -.27 General anxiety symptoms (PROMIS) 53.84 71.00 469.00 .058 -.18 Depression symptoms (PROMIS) 55.11 62.14 593.00 .397 -.08 Pain catastrophizing (CSQ-R) 49.98 97.68 95.50 <.001 -.50 Pre-procedural anxiety (NARS) 52.06 82.32 296.50 <.001 -.33 Expected pain (NPRS) 52.39 81.00 329.00 .002 -.30 Outcome measures (T1): During dental procedure Pain/Discomfort (NRS) 53.45 73.68 431.50 .027 -.21 Anxiety (NARS) 51.87 84.61 278.50 <.001 -.35 NOTE: Continuous variables are presented as Mean Rank; Categorical variables are presented as n (%); sex, 0= men and 1= women; previous traumatic experience, 0= no and 1= yes; previous oral pain complaint, 0= no and 1= yes; Abbreviations: df, degrees of freedom; DFS, Dental Fear Survey; MAAS, Mindful Attention Awareness Scale; PROMIS, Patient-Reported Outcomes Measurement Information System; CSQ-R, Coping Strategies Questionnaire – revised form; NARS, Numeric Anxiety Rating Scale; NPRS, Numeric Pain Rating Scale; NRS, Numeric Rating Scale. 5. Association of baseline demographic, clinical and psychological measures with pain/ discomfort and anxiety levels during dental procedure As shown in Table 6, the levels of pain/discomfort and anxiety reported during the dental procedure are significantly correlated with each other (r=.688, p<.001). None of the demographic factors (age and sex) were significantly correlated with these outcome measures. In terms of clinical factors, patients who had a previous traumatic experience during a dental appointment had more pain/discomfort (r=302, p=.002) and anxiety (r=.356, p<.001) than those who did not. Previous oral pain complaint was significantly associated with pain/discomfort intensity (r=.400, p<.001), but not with anxiety. Regarding psychological measures, pain/discomfort reported during the dental procedure was significantly correlated with the baseline measures dental anxiety (r=.421, p<.001), the DFS subscales of avoidance (r=.458, p<.001), physiological arousal (r=.333, p<.001) and fearfulness of stimuli (r=.384, p<.001), as well as with pain catastrophizing (r=.360, p<.001), pre-procedural anxiety (r=.548, p<.001) and expected pain (r=.620, p<.001). Other psychological variables, such as mindfulness, general anxiety and depression symptoms, did not correlate significantly with pain/discomfort. 38 In a similar way, the level of anxiety reported during the dental procedure was significantly correlated with dental anxiety (r=.670, p<.001) and the respective subscales of avoidance (r=.718, p<.001), physiological arousal (r=.523, p<.001) and fearfulness of stimuli (r=.626, p<.001), as well as with general anxiety symptoms (r=.277, p=.003), depression symptoms (rsp=.237, p=0.12), pain catastrophizing (r=.420, p<.001), pre-procedural anxiety (r=.748, p<.001) and expected pain (r=.687, p<.001). The variable mindfulness did not correlate significantly with the anxiety reported during the procedure. Table 6 also reveals that dental anxiety was significantly associated with previous traumatic experience (r=.457, p<.001), as well as with its subscales of avoidance, physiological arousal and fearfulness of stimuli (r=.930, p<.001; r=.922, p<.001; r=.955, p<.001; respectively). Moreover, dental anxiety significantly correlates with all baseline psychological variables under study. Apart from the variable mindfulness, with which it shows a negative association (r=-.363, p<.001), a positive correlation is presented with the remaining variables: general anxiety symptoms (r=.304, p=.001), depression symptoms (rsp=.236, p=.013), pain catastrophizing (r=.677, p<.001), preprocedural anxiety (r=.574, p<.001) and expected pain (r=.449, p<.001). Regarding mindfulness, this variable significantly correlates with dental anxiety and the respective subscales: avoidance (r=-.312, p=.001), physiological arousal (r=-.385, p<.001) and fearfulness of stimuli (r=-.336, p<.001). Additionally, mindfulness presents a negative significant correlation with general anxiety symptoms (r=-.505, p<.001), depression symptoms (rsp =-.495, p<.001) and pain catastrophizing (r=-.354, p<.001). Besides the abovementioned significant correlation with mindfulness, general anxiety symptoms are also significantly correlated with dental anxiety and its subscales: avoidance (r=.229, p=.015), physiological arousal (r=.314, p=.001) and fearfulness of stimuli (r=.310, p=.001), as well as with depression symptoms (rsp=.628, p<.001), pain catastrophizing (r=.301, p=.001) and preprocedural anxiety (r=.302, p=.001). In addition to the significant correlations with mindfulness and general anxiety symptoms, depression symptoms are also significantly correlated with the DFS subscales of physiological arousal (rsp=.251, p=.008) and fearfulness of stimuli (rsp=.196, p=.039), and with pre-procedural anxiety (rsp=.226, p=.017). Finally, pain catastrophizing reveals a significant correlation with all three dental anxiety subscales of avoidance (r=.615, p<.001), physiological arousal (r=.622, p<.001) and fearfulness of stimuli (r=.659, p<.001), with preprocedural anxiety (r=.436, p<.001) and expected pain (r=.382, p<.001), as well as with mindfulness and general anxiety symptoms, as reported above. 39 Table 6. Pearson and point-biserial correlation coefficients between baseline demographic, clinical and psychological measures and pain/discomfort and anxiety during dental procedure 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1. Pain/discomfort T1 (NRS) 1 2. Anxiety T1 (NARS) .688*** 1 3. Age .003 .048 1 4. Sex .045 .087 -.138 1 5. Previous traumatic experience .302** .356*** .140 -.069 1 6. Previous oral pain complaint .400*** .141 -.045 -.136 .041 1 7. Anaesthesia .073 .131 -.078 -.114 .023 .314** 1 8. Dental anxiety (DFS) .421*** .670*** .097 .040 .457*** .080 -.043 1 9. Avoidance1 .458*** .718*** .073 .024 435*** .127 .078 .930*** 1 10. Physiological arousal1 .333*** .523*** .102 .043 .452*** .047 -.127 .922*** .800*** 1 11. Fearfulness of stimuli1 .384*** .626*** .097 .041 .406*** .051 -.073 .955*** .820*** .827*** 1 12. Mindfulness (MAAS) -.091 -.063 -.033 -.115 -.084 -.080 -.051 -.363*** -.312** -.385*** -.336*** 1 13. General anxiety symptoms (PROMIS) .169 .277** .151 .177 .089 .025 -.031 .304** .229* .314** .310** -.505*** 1 14. Depression symptoms (PROMIS) 2 .158 .237* .036 .075 -.009 .093 -.039 .236* .174 .251** .196* -.495*** .628*** 1 15. Pain catastrophizing (CSQ-R) .360*** .420*** .185 .093 .446*** .082 .032 .677*** .615*** .622*** .659*** -.354*** .301** .134 1 16. Pre-procedural anxiety (NARS) .548*** .748*** .204* .133 .288** .178 .087 .574*** .582*** .488*** .536*** -.050 .302** .226* .436*** 1 17. Expected pain (NPRS) .620*** .687*** .078 .047 .273** .294** .170 .449*** .469*** .335*** .437*** -.071 .167 .163 .382*** .770*** 1 *p<.05, **p<.01, ***p<.001 NOTE. T1, during the dental procedure; sex, 0= men and 1= women; previous traumatic experience, 0= no and 1= yes; previous oral pain complaint, 0= no and 1= yes; anaesthesia, 0= no and 1= yes; Abbreviations: NRS, Numeric Rating Scale; NARS, Numeric Anxiety Rating Scale; DFS, Dental Fear Survey; MAAS, Mindful Attention Awareness Scale; PROMIS, Patient-Reported Outcomes Measurement Information System; CSQ-R, Coping Strategies Questionnaire – revised form; NPRS, Numeric Pain Rating Scale. 1 Dental Fear Survey Subscale 2 For the variable depression Spearman correlation was used 40 6. Prediction of pain/discomfort and anxiety levels during dental procedure To determine the predictors of pain/discomfort and anxiety levels during the dental procedure, separate hierarchical multiple regression analyses were conducted (Tables 7 and 8). In each regression, age and sex were included in the first block. For pain/discomfort prediction, previous oral pain complaint was added to the second block due to its significant correlation with the dependent variable (DV) (r=.400, p<.001). For the third block, dental anxiety and pain catastrophizing were selected along with pre-procedural anxiety and expected pain. However, dental anxiety and pain catastrophizing presented high correlation between them (r=.677 ≃.7), what made that pain catastrophizing was excluded due to lower correlation with DV (r=.360) than dental anxiety (r=.421). In the same way, preprocedural anxiety and expected pain were highly correlated (r=.770), and pre-procedural anxiety was thus excluded from this block as it presented values of correlation with DV (r=.548) lower than expected pain (r=.620). For anxiety prediction, previous traumatic experience was added in the second block due to a significant correlation with the DV (r=.356, p<.001). For the third block, four variables were selected: dental anxiety, pain catastrophizing, pre-procedural anxiety and expected pain. For the same reason mentioned above, pain catastrophizing was excluded from this step due to lower correlation with DV (r=.420) than dental anxiety (r=.670). Additionally, expected pain was also excluded as it presented values of correlation with DV (r=.687) lower than pre-procedural anxiety (r=.748). General anxiety and depression symptoms did not enter the model since only 7 variables were selected from the beginning and these were the psychological variables with lower correlation with the DV (r=.277 and rsp=.237 respectively). Table 7 shows the results of the hierarchical multiple regression model for the prediction of pain/discomfort intensity during dental procedures. All the assumptions were checked and fulfilled. Age and sex in the first block did not reach statistical significance (ß=.010, p=.922; ß=.047, p=.632, respectively). When adding previous oral pain complaint (block 2), it emerged as a significant predictor (ß=.416, p<.001), accounting for an additional 16.9% of the variance. Psychological variables, dental anxiety and expected pain, were entered in the third block, both yielding significance (ß=.197, p=.015 and ß=.458, p<.001, respectively), and explaining an additional 29.9% of the variance in pain/discomfort intensity. The final model explained 44.5% of the variance with previous oral pain complaint keeping its significance (ß =.253, p=.001). 41 Table 7. Hierarchical multiple regression results for predictors of pain/discomfort level during dental procedure (N = 111) Variables B Beta (ß) t CI 95% [LL, UL] R2 Adj. R2 ∆R2 ∆F Block 1 .002 -.016 .002 .116 Age .001 .010 .098 [-.027; .030] Sex .199 .047 .480 [-.624; 1.023] Block 2 .171 .148 .169 21.849*** Age .005 .037 .098 [-.020; .031] Sex .458 .107 .480 [-.304; 1.220] Previous oral pain complaint 2.158 .416 4.674*** [1.243; 3.073] Block 3 (Final model) .470 .445 .299 29.653*** Age -.005 -.034 -2.034 [-.026; .016] Sex .195 .046 .049 [-.424; .814] Previous oral pain complaint 1.318 .253 3.356** [.539; 2.096] Dental anxiety .023 .197 2.464* [.005; .042] Expected pain .422 .458 5.485*** [.269; .574] *p<.05, **p<.01, ***p<.001 NOTE. sex, 0 = men and 1 = women; previous pain complaint, 0 = no and 1 = yes. Abbreviations: CI, confidence interval; LL, lower limit; UL, upper limit; Adj. R2, Adjusted R2 The results of the multiple hierarchical regression for the prediction of anxiety intensity during dental procedures are presented in Table 8. The assumptions to perform regression were checked. Looking at the standardised residuals, two participants had values greater than 3 and a decision was made to remove these two outliers, resulting in the fulfilment of all the assumptions. In this model, age and sex entered in the first block, without reaching a statistical significance (ß=.038, p=.711; ß=.108, p=.288, respectively). Previous traumatic experience was added in the second block demonstrating to be a significant predictor (ß=.359, p<.001), explaining 12.6% of the variance in anxiety. Dental anxiety and pre-procedural anxiety were included in the last block, both emerging as significant predictors (ß=.288, p<.001 and ß=.639, p<.001; respectively) and adding 58.4% to the explained variance. In the final model, previous traumatic experience ceased to be significant (ß=.068, p=.257) while age became significant (ß=-.113, p=.045). This final model explained 70.8% of the total variance in anxiety with dental anxiety and pre-procedural anxiety remaining the best predictors of anxiety during dental procedures. 42 Table 8. Hierarchical multiple regression results for predictors of anxiety level during dental procedure (N = 102) Variables B Beta (ß) t CI 95% [LL, UL] R2 Adj. R2 ∆R2 ∆F Block 1 .012 -.008 .012 .593 Age .006 .038 .371 [-.026; .038] Sex .494 .108 1.068 [-.424; 1.411] Block 2 .138 .112 .126 14.344*** Age .000 .002 .024 [-.029; .030] Sex .631 .138 1.449 [-.233; 1.496] Previous traumatic experience 1.871 .359 3.787*** [.891; 2.851] Block 3 (Final model) .772 .708 .584 100.980*** Age -.018 -.113 -2.034* [-.035; .000] Sex .012 .003 .049 [-.493; .518] Previous traumatic experience .357 .068 1.141 [-.264; .978] Dental anxiety .038 .288 4.170*** [.020; .056] Pre-procedural anxiety .604 .639 9.582*** [.479; .729] *p<.05, ***p<.001 NOTE. sex, 0 = men and 1 = women; previous traumatic experience, 0 = no and 1 = yes. Abbreviations: CI, confidence interval; LL, lower limit; UL, upper limit; Adj. R2, Adjusted R2 43 DISCUSSION This study aimed to investigate the association between dental anxiety, pain and mindfulness in patients undergoing dental procedures, and to explore the predictors of pain, discomfort and anxiety during the appointment. The results showed that higher dental anxiety is significantly associated with lower mindfulness levels, more general anxiety and depression symptoms, increased pain catastrophizing levels, more pre-procedural anxiety and expected pain. Furthermore, this study revealed the significant main influence of psychological factors in the prediction of pain/discomfort and anxiety during dental appointment. For pain/discomfort levels reported during the dental procedure, previous oral pain complaint, dental anxiety and expected pain were the significant predictors. For anxiety levels, dental anxiety and pre-procedural anxiety emerged as significant psychological predictors, along with age. These findings could be useful for the design of interventions targeting pain, discomfort and anxiety management in dental context and ultimately promote patients’ adherence to dental care and improve general oral health of the population. 1. Sociodemographic, clinical and dental appointment characteristics Looking at the demographic characteristics of the sample, most of the participants in the study were female. The same trend was observed in other studies conducted in dental clinics (25,57,148,149). Higher attendance of women may occur due to a greater concern with health and aesthetics in this group (150). Cultural factors may also justify this greater female demand, as women are more predisposed to seek clinical care (15,150). With respect to variables related to dental appointment, just over a fifth of patients reported having experienced a previous traumatic dental experience. Another study (148) conducted with a Portuguese sample reported a higher percentage of positive answers to this question (48%). According to that study (148), there is a significant association between individuals with previous traumatic experience and those who avoid the dental appointment due to fear. Indeed, most of the individuals that used to miss dental appointments reported having suffered a previous traumatic experience and a tendency to postpone the appointment, until the onset of painful symptoms. In addition, another study revealed that those who did not have previous traumatic experiences were less dental anxious (26). Similar conclusions can be drawn from current study, where the previous traumatic experience is associated with higher levels of dental 44 anxiety. Together, these findings support the direct conditioning pathway for the development of dental anxiety. It seems likely that, after a negative experience in the dental office, patients begin to associate all or most of dentistry stimuli as fearful or aversive (2). Findings from this study also showed that the majority of the participants visited the dentist with some regularity: every six months or once a year, as recommended by international and national dental federations (151–153). The same tendency was reported by Siviero et al. (2008)(154) and Ferreira et al. (2008) (148), where more than half of the evaluated patients reported to visit the dentist at least once a year. Regarding the type of dental treatment administered, conservative and prophylactic treatments (checkup, scaling, dental restoration, orthodontic, fixed and removable prosthesis) were the most frequent in current study, often planned as a routine procedure, which might explain that the majority of the participants did not present any oral pain complaint pre-treatment and reported lower levels of pain and anxiety during the dental procedure. Actually, previous studies show that patients undergoing more invasive dental procedures such as dental extractions and root canal therapy, tend to experience more pain (155–157) and anxiety (127) during the appointment. However, some patients also report experiencing no pain at all, even when undergoing these more invasive procedures (155). Congruently, in the present study, patients scheduled for invasive/emergency procedures only differed from patients undergoing conservative/prophylactic treatments in terms of pain catastrophizing, with no significant differences on the other variables, namely on pain/discomfort and anxiety reported during the procedure. One possible explanation is that, although patients tend to catastrophize previous to more invasive procedures, the administration of local anaesthetics prior to these treatments decreases, or even eliminates, the pain sensation that may be caused. Additionally, several patients used to meet the same dentist or the same clinic regularly, which may have contributed to a successful and trustful patientdentist relationship. Establishing a good communication with the patient may induce feelings of ease and confidence, which can help to reduce anxiety and possible fears in relation to the treatment approach (158,159). Even when facing more complex and possibly painful treatments, the trust already established with the dentist may help to mitigate anxiety and possibly also the pain/discomfort intensity. 2. Psychological and pain characteristics Concerning psychological characteristics, participants revealed low levels of dental anxiety, without clinically relevant general anxiety or depressive symptoms, as well as low tendency for pain catastrophizing. The majority scored as having high mindfulness skills. Moreover, participants also 45 reported low levels of pre-procedural anxiety and expected pain before the dental procedure. Lastly, few patients reported oral pain complaint pre-treatment. About dental anxiety, the scores reported in current work are similar to those reported by other authors using the Dental Fear Survey (DFS) questionnaire (127,160). Additionally, the prevalence of high dental anxious individuals found in current study (12.6%; DFS>60) is within the interval of 10-20% (11,12,15,16) shown in the literature for adult populations. It is although below the figures reported in another study with Portuguese patients, where 23.3% presented "high dental anxiety" (17). A possible explanation for this discrepancy is that in that study 33% of patients had suffered a previous traumatic experience in a dental office (17). Given the reported association between traumatic experiences and dental anxiety (2,3,19), it is likely that the high frequency of these traumatic experiences has contributed to increased dental anxiety levels in the abovementioned study (17). Consistently, patients in current study with high dental anxiety have undergone more often a previous dental traumatic experience. For the variable mindfulness, the mean level reported by this sample of participants was surprisingly high, when compared with the results reported by other studies using the same questionnaire, the Mindful Attention Awareness Scale (MAAS) (130,161–165). This was an unexpected result, since a literature search on articles using MAAS questionnaire with more than 6000 individuals, showed that participants do not generally have mindfulness scores as high as those achieved in the present study (130,161–168). Nevertheless, it may be the case that most participants of current study did actually possess high mindfulness skills. One could also wonder whether participants understood the items appropriately, despite the fact that in the pilot study no doubt or question was posed concerning those. Regardless of these considerations, it should be noted that the reduced variability of responses to MAAS in this study may preclude findings regarding the potential association between this variable and the outcomes under study. The results also indicate that the individuals engaged in this study seem to have good mental health indicators. On average, patients’ levels of general anxiety and depression symptoms were below the cut point of 8 for relevant clinical symptomatology (133). Thus, the great majority of the participants did not present noticeable anxiety (75.68%) or depressive symptoms (89.19%). Regarding pain catastrophizing, participants revealed low levels of this maladaptive pain-coping strategy, corroborating the results published in previous Portuguese studies conducted on postsurgical pain context (134,135,169–172), where the same scale (Coping Strategies Questionnaire - revised form, CSQ-R) was used. 52 visiting a dentist were approached, while patients with an aversion to dental visits were probably underrepresented in the sample. Finally, a greater range and hence greater complexity of treatment procedures would have been preferred to better account for their influence on the outcomes. 53 CONCLUSIONS AND IMPLICATIONS FOR CLINICAL PRACTICE The present study focused on variables that have been scarcely analysed in scientific research, such as the association between mindfulness and dental anxiety and the assessment of discomfort during dental procedures. The results identified psychological factors influencing pain/discomfort and anxiety during dental procedures, namely expected pain, dental anxiety and pre-procedural anxiety, which can be managed beforehand with appropriate interventions. This knowledge has the potential to guide prevention and treatment strategies, aiming to improve patients’ experience in the dental office. Concerning expected pain, the present study suggests that patients who anticipated painful procedures would likely experience a greater amount of pain, and could thus benefit from interventions to decrease this variable. Dentists should be trained to better manage patients’ expectations of pain by the use of interpersonal and psychological strategies (157), besides applying effective local anaesthetic techniques. Altogether, these actions would potentially reduce patients perceptions of pain and, in the long term, improve their attitudes and beliefs regarding dental treatment (157). Dental anxiety and pre-procedural anxiety can be managed by pharmacological (sedation or general anaesthesia) and non-pharmacological interventions or a combination of both (1,18,199). In this scope, brief interventions such as “tell-show-do”, distraction, positive reinforcement, stop-signalling modelling or relaxation would be particularly useful in the dental context. These could be used by the dentist, in a timeeffective manner, before appointments with dental anxious patients. Other techniques, such as systematic desensitization, guided imagery, aromatherapy, biofeedback, hypnosis or acupuncture relaxation, have also been used (1,18,199), yet requiring more time and specific knowledge and training. Overall, these techniques aim to stimulate a positive attitude towards dentistry (206), reversing the fear/anxiety into a state of acceptance and calm (18). Regarding mindfulness, the interest in incorporating it into clinical interventions in medicine and psychology is growing (78). Although the results of present study have not revealed mindfulness as a predictor of pain/discomfort or anxiety during dental procedures, mindfulness-based approaches may also represent potentially useful strategies, particularly if we consider its association with dental anxiety. Further studies are needed to investigate the role of mindfulness among individuals with dental anxiety and to analyse the usefulness of incorporating mindfulness techniques into current treatments. 54 It is thus clear that pain and anxiety in the dental office should be controlled for as much as possible. The first step should be the use of anxiety measurement scales as a routine (207). Using a simple 0 – 10 rating scale would be an effortless and time-effective way to achieve this, but this method has been rarely reported in research papers. Already in 1988, Corah drew attention to the fact that patient satisfaction improved when dentists inquired about their anxiety (208). In fact, practitioners who address these issues demonstrate concern, promote communication and increase patients’ confidence and comfort (202). The current findings also demonstrate that age and previous oral pain complaint should be taken into consideration. Dentists should pay special attention to younger patients, who seem to have higher anxiety levels, as well as to patients complaining about pain prior to the procedure and thus more prone to experience higher levels of pain. The present study also emphasizes the importance of taking into consideration the patient's perspective to the development of patient-centred dental care (2). This development reflects the recognition that somatic and psychological processes are integrated and thereby have a great impact on anxiety and pain (10). This seems to point that the emphasis on purely biological aspects should be shifted by giving greater focus to psychological and social aspects, in the scope of a biopsychosocial approach, thus making dental care more individualized and integrated, which will promote patient's health and well-being (15). In conclusion, present findings suggest that dental patients could benefit from pre-treatment interventions, targeting pain expectations and anxiety before treatment, to reduce pain and anxiety during the treatment. More precisely, interventions targeting dental anxiety, a predictor of both outcomes, could benefit experienced pain/discomfort and anxiety, favouring a less aversive treatment and more positive experiences in the dental office. This can be promoted by incorporating behavioral and psychosocial curricula in the training of dentists, with current findings drawing attention to the need of implementing such in Portuguese dental medical schools. Ultimately, this could contribute to improve patients’ adherence to dental care and improve general oral health of the population. 55 REFERENCES 1. Appukuttan DP. Strategies to manage patients with dental anxiety and dental phobia: Literature review. Clin Cosmet Investig Dent. 2016;8:35–50. 2. Morgan AG, Porritt J. Background and prevalence of dental fear and anxiety. In: Dental fear and anxiety in pediatric patients. Springer International Publishing; 2017. p. 3–19. 3. Facco E, Zanette G. The odyssey of dental anxiety: From prehistory to the present. A narrative review. Front Psychol. 2017;8:1–15. 4. Association AP. Anxiety Disorders. In: Publishing AP, editor. Diagnostic and statistical manual of mental disorders. 5 th. Washington, DC; 2013. p. 189–234. 5. Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015;17(3):327–35. 6. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21(3):169–84. 7. Caldas de Almeida JM, Xavier M, Cardoso G, Gonçalves Pereira M, Gusmão R, Corrêa B, et al. Estudo epidemiológico nacional de saúde mental. Faculdade de Ciências Médicas Universidade Nova de Lisboa, editor. Lisboa; 2013. 8. Bystritsky A, Khalsa SS, Cameron ME, Schiffman J. Current diagnosis and treatment of anxiety disorders. Pharm Ther. 2013;38(1):30–44. 9. Corrigan PW, Druss BG, Perlick DA. The impact of mental illness stigma on seeking and participating in mental health care. Psychol Sci Public Interes Suppl. 2014;15(2):37–70. 10. Öst L-G, Skaret E. Cognitive behavioral therapy for dental phobia and anxiety. John Wiley & Sons; 2013. 11. White AM, Giblin L, Boyd LD. The prevalence of dental anxiety in dental practice settings. J Dent Hyg JDH. 2017;91(1):30–4. 12. Stefano R De. Psychological factors in dental patient care: Odontophobia. Medicina (B Aires). 2019;55(10):678. 13. Jaakkola S, Rautava P, Alanen P, Aromaa M, Pienihäkkinen K, Räihä H. Dental fear: One single clinical question for measurement. Open Dent J. 2009;3:161–6. 14. Stan D, Voicu DF. Dental Fear - Prevalence and ways to combat it. Brain Broad Res arteficial Intell Neurosci. 2020;11(1Sup2):51–6. 15. Queiroz MF, Verli FD, Marinho SA, Paiva PCP, Santos SMC, Soares JA. Pain, anxiety and quality of life related to the oral health of patients treated in a dental emergency clinic. Cien Saude Colet. 2019;24:1277– 56 86. 16. Jevean P, Ramseier C. Management of dental anxiety - a cross-sectional survey in private dental practices in the Swiss Romandy. Swiss Dent J. 2020;4:308–20. 17. Silva ACM. Medo e ansiedade dentária: Uma realidade. [Porto]: Universidade Fernando Pessoa; 2012. 18. Carter AE. Pathways of fear and anxiety in dentistry: A review. World J Clin Cases. 2014;2(11):642. 19. Ravishankar RKS. Anxiety and pain managment in dental office. Int J Sci Dev Res. 2020;5(2):220–6. 20. Cardaciotto L, Herbert JD, Forman EM, Moitra E, Farrow V. The assessment of present-moment awareness and acceptance: The philadelphia mindfulness scale. Assessment. 2008;15(2):204–23. 21. Beaudette JR, Fritz PC, Sullivan PJ, Piccini A, Ward WE. Investigation of factors that influence pain experienced and the use of pain medication following periodontal surgery. J Clin Periodontol. 2018;45(5):578–85. 22. Edmunds R, Buchanan H. Cognitive vulnerability and the aetiology and maintenance of dental anxiety. Community Dent Oral Epidemiol. 2012;40:17–25. 23. Afroz S, Rathi S, Rajput G, Rahman SA. Dental esthetics and its impact on psycho-social well-being and dental self confidence: A campus based survey of north indian university students. J Indian Prosthodont Soc. 2013;13(4):455–60. 24. Daniel S, Harfst S, Wilder R. Mosby’s dental hygiene concepts, cases, and competencies. 2nd ed. St. Louis: Mosby, Inc.; 2008. 754 p. 25. Omezli MM, Torul D, Kahveci K. Does watching video increase the perioperative anxiety in patients undergoing third molar surgery? A randomized trial. J Oral Maxillofac Surg. 2020;78(2):216.e1-216.e9. 26. Caltabiano ML, Croker F, Page L, Sklavos A, Spiteri J, Hanrahan L, et al. Dental anxiety in patients attending a student dental clinic. BMC Oral Health. 2018;18(1):1–8. 27. Fédération Dentaire Internationale. Oral Infection / Inflammation as a Risk Factor for Systemic Diseases. FDI. 2013. p. 2011–2. 28. Ramesh S, Neelakantan P. Systemic diseases and oral health. Indian J Med Spec. 2014;5(2):107–11. 29. Nazir MA, Izhar F, Akhtar K, Almas K. Dentists’ awareness about the link between oral and systemic health. J Fam Community Med. 2019;26(3):206–12. 30. Sanchez P, Everett B, Salamonson Y, Ajwani S, Bhole S, Bishop J, et al. Oral health and cardiovascular care: Perceptions of people with cardiovascular disease. PLoS One. 2017;12(7):e0181189. 31. Kurki P, Korhonen M, Honkalampi K, Suominen AL. Patients’ multifaceted views of dental fear in a diagnostic interview. Acta Odontol Scand. 2021;79(3):194–204. 32. Polat Ö. Pain and discomfort after orthodontic appointments. Semin Orthod. 2007;13(4):292–300. 33. Ringkamp M, Raja SN, Campbell JN, Meyer RA. Peripheral mechanisms of cutaneous nociception. In: McMahon S, Koltzenburg M, Tracey I, Turk DC, editors. Wall & Melzack’s textbook of pain. 6th ed. Philadelphia: Elsevier Health Sciences; 2013. p. 1–30. 57 34. Cohen M, Quintner J, Van Rysewyk S. Reconsidering the international association for the study of pain definition of pain. Pain Reports. 2018;3(2):1–7. 35. Raja S, Carr D, Cohen M, Finnerup N, Flor H, Gibson S, et al. The revised international association for the study of pain definition of pain: Concepts, challenges, and compromises. Pain. 2020;161(9):1976–82. 36. Merskey H, Bogduk N. “Part III: Pain terms, a current list with definitions and notes on usage.” In: Taxonomy ITF on, editor. Classification of Chronic Pain. second. IASP Press; 1994. p. 209–14. 37. McCaffery M. Nursing practice theories related to cognition, bodily pain, and man-environment interactions. UCLA Stude. Los Angeles; 1968. 38. Flor H, Turk DC. Cognitive and learning aspects. In: McMahon S, Koltzenburg M, Tracey I, Turk DC, editors. Wall & Melzack’s textbook of pain. 6th ed. Philadelphia: Elsevier Health Sciences; 2013. p. 256–72. 39. Rainville P. Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol. 2002;12(2):195– 204. 40. Melzack R. Pain - an overview. Acta Anaesthesiol Scand. 1999;43(9):880–4. 41. Chapman C. Pain perception, affective mechanisms, and conscious experience. In: Craig K, editor. Pain: Psychological perspectives. Lawrence Erlbaum Associates; 2004. 42. Melzack R, Wall PD. Pain mechanisms - a new theory. Science. 1965;150(3699):971–9. 43. Almeida A, Leite-Almeida H, Tavares I. Medullary control of nociceptive transmission: Reciprocal dual communication with the spinal cord. Drug Discov Today Dis Mech. 2006;3(3):305–12. 44. Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest. 2010;120(11):3779–87. 45. Melzack R. From the gate to the neuromatrix. Pain. 1999;82(SUPPL.1):121–6. 46. Melzack R, Casey KL. Sensory, motivational and central control determinants of chronic pain: a new conceptual model. In: Kenshalo D, editor. International Symposium on the Skin Senses. Springfield: Charles C Thomas; 1968. p. 423–35. 47. Cho I-C, Min SK. Proposed new pathophysiology of chronic prostatitis/chronic pelvic pain syndrome. Urogenit Tract Infect. 2015;10(2):92. 48. Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: Scientific advances and future directions. Psychol Bull. 2007;133(4):581–624. 49. Papadimitriou GN. The “Biopsychosocial model”: 40 years of application in Psychiatry. Psychiatr Psychiatr. 2020;28(2):107–10. 50. Svensson L, Hakeberg M, Wide U. Dental pain and oral health-related quality of life in individuals with severe dental anxiety. Acta Odontol Scand. 2018;76(6):401–6. 51. Pau AKH, Croucher R, Marcenes W. Prevalence estimates and associated factors for dental pain: A review. Oral Health Prev Dent. 2003;1(3):209–20. 52. Shaefer JR, Khawaja SN, Bavia PF. Sex, gender, and orofacial pain. Dent Clin North Am. 2018;62(4):665– 82. 58 53. Hossain MZ, Bakri MM, Yahya F, Ando H, Unno S, Kitagawa J. The role of transient receptor potential (TRP) channels in the transduction of dental pain. Int J Mol Sci. 2019;20(3):1–31. 54. Vickers ER, Zakrzewska JM. Dental causes of orofacial pain. In: Zakrzewska JM, editor. Orofacial pain. Oxford University Press; 2013. p. 69–82. 55. Erdogan O, Malek M, Janal MN, Gibbs JL. Sensory testing associates with pain quality descriptors during acute dental pain. Eur J Pain. 2019;23(9):1701–11. 56. Miotto MHM de B, Silotti JCB, Barcellos LA. Dor dentária como motivo de absenteísmo em uma população de trabalhadores. Cien Saude Colet. 2012;17:1357–63. 57. Melo P, Marques S, Silva OM. Portuguese self-reported oral-hygiene habits and oral status. Int Dent J. 2017;67(3):139–47. 58. Kumarswamy A. Multimodal management of dental pain with focus on alternative medicine: A novel herbal dental gel. Contemp Clin Dent. 2016;7(2):131–9. 59. Dabiri D, Harper DE, Kapila Y, Kruger GH, Clauw DJ, Harte S. Applications of sensory and physiological measurement in oral-facial dental pain. Spec Care Dent. 2018;38(6):395–404. 60. Närhi M, Bjørndal L, Pigg M, Fristad I, Haug SR. Acute dental pain I: Pulpal and dentinal pain. Nor Tann Tid. 2016;126(1):10–8. 61. Lin C, Niddam D, Hsu M, Hsieh J. Pain catastrophizing is associated with dental pain in a stressful context. J Dent Res. 2013;92(2):130–5. 62. Zhang X, Wang B, Dds BNSQ, Dds YG, Dds JSHL. A study on the prevalence of dental anxiety, pain perception, and their interrelationship in Chinese patients with oral implant surgery. Clin Implant Dent Relat Res. 2019;21(3):428–35. 63. Suresh S, Soniya S, Rajendran G. Gender based comparison of impact of dental pain on the quality of life among out patients of a private dental college in Tamil Nadu. J Indian Assoc Public Heal Dent. 2015;13(4):486–91. 64. Sullivan MJ, Neish N. Catastrophic thinking and the experience of pain during dental procedures. J Indiana Dent Assoc. 2000;79(4):16–9. 65. Philpott R, Gulabivala K, Leeson R, Ng YL. Prevalence, predictive factors and clinical course of persistent pain associated with teeth displaying periapical healing following nonsurgical root canal treatment: A prospective study. Int Endod J. 2019;52(4):407–15. 66. Lin CS. Pain catastrophizing in dental patients. J Am Dent Assoc. 2013;144(11):1244–51. 67. Sullivan MJL, Neish NR. Catastrophizing, anxiety and pain during dental hygiene treatment. Community Dent Oral Epidemiol. 1998;26(5):344–9. 68. Beck VJ, Farella M, Chandler NP, Kieser JA, Thomson WM. Factors associated with pain induced by orthodontic separators. J Oral Rehabil. 2014;41(4):282–8. 69. Altan A, Akkoç S, Erdil A, Çolak S, Demir O, Altan H. Effects of pain catastrophizing and anxiety on analgesic 59 use after surgical removal of impacted mandibular third molars. J Dent Anesth Pain Med. 2019;19(6):379. 70. Ashkenazy S, DeKeyser Ganz F. The differentiation between pain and discomfort: A concept analysis of discomfort. Pain Manag Nurs. 2019;20(6):556–62. 71. Chaves AM, Loffredo L de CM, Valsecki Júnior A, Chaves OM, Campos JÁDB. Estudo epidemiológico da ansiedade dos pacientes ao tratamento odontológico. Rev Odontol da UNESP. 2006;35(4):263–8. 72. van Bochove JA, van Amerongen WE. The influence of restorative treatment approaches and the use of local analgesia, on the children’s discomfort. Eur Arch Paediatr Dent. 2006;7(1):11–6. 73. Li DT, Puntillo K. A pilot study on coexisting symptoms in intensive care patients. Appl Nurs Res. 2006;19(4):216–9. 74. Davoudi A, Rismanchian M, Akhavan A, Nosouhian S, Bajoghli F, Haghighat A, et al. A brief review on the efficacy of different possible and nonpharmacological techniques in eliminating discomfort of local anesthesia injection during dental procedures. Anesth Essays Res. 2016;10(1):13–6. 75. Gibson J. Mindfulness, interoception, and the body: A contemporary perspective. Front Psychol. 2019;10(2012). 76. Sanada K, Montero-Marin J, Barceló-Soler A, Ikuse D, Ota M, Hirata A, et al. Effects of mindfulness-based interventions on biomarkers and low-grade inflammation in patients with psychiatric disorders: A metaanalytic review. Int J Mol Sci. 2020;21(7):1–20. 77. Lindsay EK, Creswell JD. Mechanisms of mindfulness training: Monitor and Acceptance Theory (MAT). Clin Psychol Rev. 2017;51:48–59. 78. Kabat-Zinn J. Mindfulness-based interventions in context: Past, present, and future. Clin Psychol Sci Pract. 2003;10(2):144–56. 79. Ludwig DS, Kabat-Zinn J. Mindfulness in medicine. JAMA. 2008;300(11):1350–2. 80. Bishop SR, Lau M, Shapiro S, Carlson L, Anderson ND, Carmody J, et al. Mindfulness: A proposed operational definition. Clin Psychol Sci Pract. 2004;11(3):230–41. 81. Bush HE, Rossy L, Mintz LB, Schopp L. Eat for life: A work site feasibility study of a novel mindfulnessbased intuitive eating intervention. Am J Heal Promot. 2014;28(6):380–8. 82. Bowen S, Chawla N, Collins SE, Witkiewitz K, Hsu S, Grow J, et al. Mindfulness-based relapse prevention for substance use disorders: A pilot efficacy trial. Subst Abus. 2009;30(4):295–305. 83. Carlson LE, Garland SN. Impact of Mindfulness-Based Stress Reduction (MBSR) on sleep, mood, stress and fatigue symptoms in cancer outpatients. Int J Behav Med. 2005;12(4):278–85. 84. Carlson LE, Speca M, Patel KD, Goodey E. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients. Psychosom Med. 2003;65(4):571–81. 85. Norman J, Fu M, Ekman I, Björck L, Falk K. Effects of a mindfulness-based intervention on symptoms and signs in chronic heart failure: A feasibility study. Eur J Cardiovasc Nurs. 2018;17(1):54–65. 60 86. Röthlin P, Birrer D, Horvath S, Grosse Holtforth M. Psychological skills training and a mindfulness-based intervention to enhance functional athletic performance: Design of a randomized controlled trial using ambulatory assessment. BMC Psychol. 2016;4(1):39. 87. Sibinga EMS, Webb L, Ghazarian SR, Ellen JM. School-based mindfulness instruction: An RCT. Pediatrics. 2016;137(1). 88. Kabat-Zinn J, Chapman-Waldrop A. Compliance with an outpatient stress reduction program: Rates and predictors of program completion. J Behav Med. 1988;11(4):333–52. 89. Crane RS, Brewer J, Feldman C, Kabat-Zinn J, Santorelli S, Williams JMG, et al. What defines mindfulnessbased programs? The warp and the weft. Psychol Med. 2017;47(6):990–9. 90. Teasdale JD, Segal Z V., Williams JMG, Ridgeway VA, Soulsby JM, Lau MA. Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin Psychol. 2000;68(4):615–23. 91. Teixeira RJ, Pereira MG. Examining mindfulness and its relation to self-differentiation and alexithymia. Mindfulness (N Y). 2015;6(1):79–87. 92. Kladnitski N, Smith J, Uppal S, James MA, Allen AR, Andrews G, et al. Transdiagnostic internet-delivered CBT and mindfulness-based treatment for depression and anxiety: A randomised controlled trial. Internet Interv. 2020;20:100310. 93. Querstret D, Morison L, Dickinson S, Cropley M, John M. Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy for psychological health and well-being in nonclinical samples: A systematic review and meta-analysis. Int J Stress Manag. 2020;27(4):394–411. 94. La Torre G, Raffone A, Peruzzo M, Calabrese L, Cocchiara RA, D’Egidio V, et al. Yoga and mindfulness as a tool for influencing affectivity, anxiety, mental health, and stress among healthcare workers: Results of a single-arm clinical trial. J Clin Med. 2020;9(4):1037. 95. Rönnlund M, Koudriavtseva A, Germundsjö L, Eriksson T, Åström E, Carelli MG. Mindfulness promotes a more balanced time perspective: Correlational and intervention-based evidence. Mindfulness (N Y). 2019;10(8):1579–91. 96. Waszczuk MA, Zavos HMS, Antonova E, Haworth CM, Plomin R, Eley TC. A multivariate twin study of trait mindfulness, depressive symptoms and anxiety sensitivity. Depress Anxiety. 2015;32(4):254–61. 97. Greeson JM, Chin GR. Mindfulness and physical disease: A concise review. Curr Opin Psychol. 2019;28:204–10. 98. Plaza I, Demarzo MMP, Herrera-Mercadal P, García-Campayo J. Mindfulness-based mobile applications: Literature review and analysis of current features. J Med Internet Res. 2013;15(11):1–19. 99. Ramaci T, Bellini D, Presti G, Santisi G. Psychological flexibility and mindfulness as predictors of individual outcomes in hospital health workers. Front Psychol. 2019;10:1–12. 100. Beerse ME, Van Lith T, Stanwood G. Therapeutic psychological and biological responses to mindfulness- 61 based art therapy. Stress Heal. 2020;36(4):419–32. 101. Crowley C, Kapitula LR, Munk D. Mindfulness, happiness, and anxiety in a sample of college students before and after taking a meditation course. J Am Coll Heal. 2020;1–8. 102. Ghawadra SF, Lim Abdullah K, Choo WY, Danaee M, Phang CK. The effect of mindfulness‐based training on stress, anxiety, depression and job satisfaction among ward nurses: A randomized control trial. J Nurs Manag. 2020;28(5):1088–97. 103. Roy A, Druker S, Hoge EA, Brewer JA. Physician anxiety and burnout: Symptom correlates and a prospective pilot study of app-delivered mindfulness training. JMIR mHealth uHealth. 2020;8(4):e15608. 104. Hoge EA, Hölzel BK, Marques L, Metcalf CA, Brach N, Lazar SW, et al. Mindfulness and self-compassion in generalized anxiety disorder: Examining predictors of disability. Evid Based Complement Altern Med. 2013;2013:576258. 105. Curtin KB, Norris D. The relationship between chronic musculoskeletal pain, anxiety and mindfulness : Adjustments to the fear-avoidance model of chronic pain. Scand J Pain. 2017;17:156–66. 106. Di Giuseppe M, Ciacchini R, Piarulli A, Nepa G, Conversano C. Mindfulness dispositions and defense style as positive responses to psychological distress in oncology professionals. Eur J Oncol Nurs. 2019;40:104– 10. 107. Mazaheri M. Difficulties in emotion regulation and mindfulness in psychological and somatic symptoms of functional gastrointestinal disorders. 2015;9(4):0–6. 108. Nekić M, Mamić S. Intolerance of uncertainty and mindfulness as determinants of anxiety and depression in female students. Behav Sci (Basel). 2019;9(12):135. 109. Tubbs JD, Savage JE, Adkins AE, Amstadter AB, Dick DM. Mindfulness moderates the relation between trauma and anxiety symptoms in college students. J Am Coll Heal. 2019;67(3):235–45. 110. Jaiswal S, Muggleton NG, Juan CH, Liang WK. Indices of association between anxiety and mindfulness: A guide for future mindfulness studies. Personal Neurosci. 2019;2(e9):1–11. 111. Shires A, Sharpe L, Davies JN, Newton-John TRO. The efficacy of mindfulness-based interventions in acute pain: A systematic review and meta-analysis. Pain. 2020;161(8):1698–707. 112. Hilton L, Hempel S, Ewing BA, Apaydin E, Xenakis L, Newberry S, et al. Mindfulness meditation for chronic pain: Systematic review and meta-analysis. Ann Behav Med. 2017;51(2):199–213. 113. Izgu N, Gok Metin Z, Karadas C, Ozdemir L, Metinarikan N, Corapcıoglu D. Progressive muscle relaxation and mindfulness meditation on neuropathic pain, fatigue, and quality of life in patients with type 2 diabetes: A randomized clinical trial. J Nurs Scholarsh. 2020;52(5):476–87. 114. Garland EL, Baker AK, Larsen P, Riquino MR, Priddy SE, Thomas E, et al. Randomized controlled trial of brief mindfulness training and hypnotic suggestion for acute pain relief in the hospital setting. J Gen Intern Med. 2017;32(10):1106–13. 115. Schütze R, Rees C, Preece M, Schütze M. Low mindfulness predicts pain catastrophizing in a fear- 68