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1.  Late cortical positivity and cardiac responsitivity in female dental phobics when exposed to phobia-relevant pictures 
Dental phobia is currently classified as a specific phobia of the blood-injection-injury (BII) subtype. In another subtype, animal phobia, enhanced amplitudes of late event-related potentials have consistently been identified for patients during passive viewing of disorder-relevant pictures. However, this has not been shown for BII phobics, and studies with dental phobics are lacking. Findings on cardiac responses in BII phobia during exposure are heterogeneous, as some studies showed a diphasic pattern of heart rate acceleration and deceleration, whereas others observed pure acceleration. In contrast, heart rate increase has consistently been shown for dental phobics, resembling the reaction of animal phobics. Moreover, the BII subtype is characterized by elevated disgust reactivity whereas the role of habitual disgust proneness in dental phobia is unclear.
We recorded the electroencephalogram and the electrocardiogram from 18 dental phobic and 18 healthy women while they watched pictures depicting dental treatment, disgust, fear and neutral items.
Phobics relative to controls showed an enhanced late positive potential (300–700 ms) and heart rate acceleration towards phobic material, reflecting motivated attention and fear. Affective ratings revealed that dental phobics experienced significantly higher levels of fear than disgust during exposure to phobia-relevant material. Patients' elevated habitual disgust proneness was restricted to specific domains, such as the oral incorporation of offensive objects.
The psychophysiology of dental phobia resembles the fear-dominated subtypes of specific phobia reported in earlier studies. Future studies should continue to investigate whether the current classification of this disorder as BII phobia needs to be reconsidered.
Research Highlights
►Dental phobics show enhanced late positivity during symptom provocation. ►Dental phobics display heart rate acceleration during symptom provocation. ►Dental phobics show domain-specifically enhanced disgust sensitivity. ►The current classification of dental phobia should be reconsidered.
PMCID: PMC3072525  PMID: 21238507
Dental phobia; EEG; ERP; Heart rate; Late positive potential; Disgust; Fear
2.  Comparison of lidocaine with and without bupivacaine for local dental anesthesia. 
Anesthesia Progress  1997;44(3):83-86.
The purpose of this study was to investigate the effectiveness of a combination of bupivacaine and lidocaine and that of lidocaine alone for local dental anesthesia. First, on different days, healthy volunteers were given 2% lidocaine with 1/80,000 epinephrine or 2% lidocaine with 1/80,000 epinephrine + 0.5% bupivacaine, after which pain was produced with a pulp tester. No difference was found in the time until onset of anesthetic effect between the preparations. However, the duration of anesthetic effect was longer with both lidocaine and bupivacaine than with lidocaine alone. Next, patients undergoing dental surgery were given one of the anesthetic preparations, after which serum concentrations of the anesthetics and epinephrine were measured. The maximal serum concentration of lidocaine was higher and was reached sooner after injection in patients receiving lidocaine alone (1.74 microgram/ml after 5 min) than in patients receiving both anesthetics (0.85 microgram/ml after 3 min). The mean maximal serum concentration of lidocaine was higher in patients receiving lidocaine alone (1.77 +/- 0.03 microgram/ml) than in those receiving both anesthetics (0.99 +/- 0.45 microgram/ml). Furthermore, the mean plasma concentration of epinephrine 1 min after injection was significantly higher in patients receiving lidocaine alone (0.671 ng/ml) than in patients receiving both lidocaine and bupivacaine (0.323 ng/ml). The results of this study suggest that the combination of lidocaine with epinephrine and bupivacaine produces lower systemic levels of the anesthetic and epinephrine and a longer duration of activity than lidocaine with epinephrine alone for local dental anesthesia.
PMCID: PMC2148928  PMID: 9481966
3.  A randomized controlled trial comparing mandibular local anesthesia techniques in children receiving nitrous oxide-oxygen sedation. 
Anesthesia Progress  2004;51(1):19-23.
The aim of this study was to test the hypothesis that dental pain control using infiltration/intrapapillary injection was less effective than inferior alveolar block/long buccal infiltration anesthesia in children. A total of 101 healthy children, aged 5-8 years, who had no contraindication for local anesthetic and who needed a pulpotomy treatment and stainless steel crown placement in a lower primary molar were studied. A 2-group randomized blinded controlled design was employed comparing the 2 local anesthesia techniques using 2% lidocaine, 1:100,000 epinephrine. All children were given 40% nitrous oxide. Children self-reported pain using the Color Analogue Scale. The study was conducted in a private pediatric dental practice in Mount Vernon, Wash. Overall pain levels reported by the children were low, and there were no differences between conditions at any point in the procedure. Pain reports for clamp placement were block/long buccal 2.8 and infiltration/intrapapillary 1.9 (P = .1). Pain reports for drilling were block/long buccal 2.0 and infiltration/intrapapillary 1.8 (P = .7). Nine percent of children required supplementary local anesthetic: 4 of 52 (7.7%) in the block/long buccal group and 5 of 49 (10.2%) in the infiltration/intrapapillary group (P = .07). The hypothesis that block/long buccal would be more effective than infiltration/intrapapillary was not supported. There was no difference in pain control effectiveness between infiltration/intrapapillary injection and inferior alveolar block/long buccal infiltration using 2% lidocaine with 1:100,000 epinephrine when mandibular primary molars received pulpotomy treatment and stainless steel crowns.
PMCID: PMC2007457  PMID: 15106686
4.  Impaired conditioned fear response and startle reactivity in epinephrine deficient mice 
Behavioural pharmacology  2013;24(1):1-9.
Norepinephrine and epinephrine signaling is thought to facilitate cognitive processes related to emotional events and heightened arousal, however, the specific role of epinephrine in these processes is less known. To investigate the selective impact of epinephrine on arousal and fear-related memory retrieval, mice unable to synthesize epinephrine (phenylethanolamine N-methyltransferase knockout, PNMT-KO) were tested in context and cued fear conditioning. To assess the role of epinephrine in other cognitive and arousal-based behaviors these mice were also tested for acoustic startle, prepulse inhibition, novel object recognition and open field activity. Our results show that compared to wild-type (WT) mice, PNMT-KO mice displayed reduced context fear but normal cued fear. Mice exhibited normal memory performance in the short-term version of the novel object recognition task suggesting PNMT mice exhibit more selective memory effects on highly emotional and/or long term memories. Similarly, open field activity was unaffected by epinephrine deficiency, suggesting differences in freezing are not related to changes in overall anxiety or exploratory drive. Startle reactivity to acoustic pulses was reduced in PNMT-KO mice while prepulse inhibition was increased. These findings provide further evidence for a selective role of epinephrine in contextual fear learning, and support its potential role in acoustic startle.
PMCID: PMC3558035  PMID: 23268986
PNMT; epinephrine; conditioned fear; memory; acoustic startle; prepulse inhibition; arousal
5.  Pharmacokinetics of Lidocaine With Epinephrine Following Local Anesthesia Reversal With Phentolamine Mesylate 
Anesthesia Progress  2008;55(2):40-48.
Phentolamine mesylate accelerates recovery from oral soft tissue anesthesia in patients who have received local anesthetic injections containing a vasoconstrictor. The proposed mechanism is that phentolamine, an alpha-adrenergic antagonist, blocks the vasoconstriction associated with the epinephrine used in dental anesthetic formulations, thus enhancing the systemic absorption of the local anesthetic from the injection site. Assessments of the pharmacokinetics of lidocaine and phentolamine, and the impact of phentolamine on the pharmacokinetics of lidocaine with epinephrine were performed to characterize this potentially valuable strategy. The blood levels of phentolamine were determined following its administration intraorally and intravenously. Additionally, the effects of phentolamine mesylate on the pharmacokinetics of intraoral injections of lidocaine with epinephrine were evaluated. Sixteen subjects were enrolled in this phase 1 trial, each receiving 4 drug treatments: 1 cartridge lidocaine/epinephrine followed after 30 minutes by 1 cartridge phentolamine (1L1P), 1 cartridge phentolamine administered intravenously (1Piv), 4 cartridges lidocaine/epinephrine followed after 30 minutes by 2 cartridges phentolamine (4L2P), and 4 cartridges lidocaine/epinephrine followed by no phentolamine (4L). Pharmacokinetic parameters estimated for phentolamine, lidocaine, and epinephrine included peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve from 0 to the last time point (AUClast) or from time 0 to infinity (AUCinf), elimination half-life (t1/2), clearance (CL), and volume of distribution (Vd). The phentolamine Tmax occurred earlier following the intravenous administration of 1Piv (7 minutes than following its submucosal administration in treatment 1L1P (15 minutes) or 4L2P (11 minutes). The phentolamine t1/2, CL, and Vd values were similar for 1L1P, 1Piv, and 4L2P. The Tmax for lidocaine occurred later and the Cmax for lidocaine was slightly higher when comparing the 4L2P treatment and the 4L treatment. The phentolamine-induced delay of the lidocaine Tmax likely represents phentolamine's ability to accelerate the systemic absorption of lidocaine from oral tissues into the systemic circulation.
PMCID: PMC2424015  PMID: 18547152
Pharmacokinetics; Dental local anesthesia; Lidocaine; Phentolamine; Epinephrine
6.  Stress-Mediated Increases in Systemic and Local Epinephrine Impair Skin Wound Healing: Potential New Indication for Beta Blockers 
PLoS Medicine  2009;6(1):e1000012.
Stress, both acute and chronic, can impair cutaneous wound repair, which has previously been mechanistically ascribed to stress-induced elevations of cortisol. Here we aimed to examine an alternate explanation that the stress-induced hormone epinephrine directly impairs keratinocyte motility and wound re-epithelialization. Burn wounds are examined as a prototype of a high-stress, high-epinephrine, wound environment. Because keratinocytes express the β2-adrenergic receptor (β2AR), another study objective was to determine whether β2AR antagonists could block epinephrine effects on healing and improve wound repair.
Methods and Findings
Migratory rates of normal human keratinocytes exposed to physiologically relevant levels of epinephrine were measured. To determine the role of the receptor, keratinocytes derived from animals in which the β2AR had been genetically deleted were similarly examined. The rate of healing of burn wounds generated in excised human skin in high and low epinephrine environments was measured. We utilized an in vivo burn wound model in animals with implanted pumps to deliver β2AR active drugs to study how these alter healing in vivo. Immunocytochemistry and immunoblotting were used to examine the up-regulation of catecholamine synthetic enzymes in burned tissue, and immunoassay for epinephrine determined the levels of this catecholamine in affected tissue and in the circulation. When epinephrine levels in the culture medium are elevated to the range found in burn-stressed animals, the migratory rate of both cultured human and murine keratinocytes is impaired (reduced by 76%, 95% confidence interval [CI] 56%–95% in humans, p < 0.001, and by 36%, 95% CI 24%–49% in mice, p = 0.001), and wound re-epithelialization in explanted burned human skin is delayed (by 23%, 95% CI 10%–36%, p = 0.001), as compared to cells or tissues incubated in medium without added epinephrine. This impairment is reversed by β2AR antagonists, is absent in murine keratinocytes that are genetically depleted of the β2AR, and is reproduced by incubation of keratinocytes with other β2AR-specific agonists. Activation of the β2AR in cultured keratinocytes signals the down-regulation of the AKT pathway, accompanied by a stabilization of the actin cytoskeleton and an increase in focal adhesion formation, resulting in a nonmigratory phenotype. Burn wound injury in excised human skin also rapidly up-regulates the intra-epithelial expression of the epinephrine synthesizing enzyme phenylethanolamine-N-methyltransferase, and tissue levels of epinephrine rise dramatically (15-fold) in the burn wounded tissue (values of epinephrine expressed as pg/ug protein ± standard error of the mean: unburned control, 0.6 ± 0.36; immediately postburn, 9.6 ± 1.58; 2 h postburn, 3.1 ± 1.08; 24 h post-burn, 6.7 ± 0.94). Finally, using an animal burn wound model (20% body surface in mice), we found that systemic treatment with βAR antagonists results in a significant increase (44%, 95% CI 27%–61%, p < 0.00000001) in the rate of burn wound re-epithelialization.
This work demonstrates an alternate pathway by which stress can impair healing: by stress-induced elevation of epinephrine levels resulting in activation of the keratinocyte β2AR and the impairment of cell motility and wound re-epithelialization. Furthermore, since the burn wound locally generates epinephrine in response to wounding, epinephrine levels are locally, as well as systemically, elevated, and wound healing is impacted by these dual mechanisms. Treatment with beta adrenergic antagonists significantly improves the rate of burn wound re-epithelialization. This work suggests that specific β2AR antagonists may be apt, near-term translational therapeutic targets for enhancing burn wound healing, and may provide a novel, low-cost, safe approach to improving skin wound repair in the stressed individual.
Rivkah Isseroff and colleagues describe how stress-induced elevation of epinephrine levels can impair the healing of burns in mice and suggest that β2 adrenergic receptor antagonists may have a role in improving skin wound repair.
Editors' Summary
Skin—the largest organ in the human body—protects the rest of the body against infection by forming an impervious layer over the whole external body surface. Consequently, if this layer is damaged by rubbing, cutting, or burning, it must be quickly and efficiently repaired. Wound repair (healing) involves several different processes. First, the clotting cascade stops bleeding at the wound site and immune system cells attracted into the site remove any bacteria or debris in the wound. Various factors are released by the immune cells and the other cells in and near the damaged area that encourage the migration of several different sorts of cells into the wound. These cells proliferate and prepare the wound for “re-epithelialization.” In this process, keratinocytes (a type of epithelial cell that makes a tough, insoluble protein called keratin; epithelial cells cover all the surfaces of the body) migrate into the wound site and form a new, intact epithelial layer. If any of these processes fail, the result can be a chronic (long-lasting) nonhealing wound. In particular, if the wound does not re-epithelialize, it remains open and susceptible to infection and loss of body fluids.
Why Was This Study Done?
One factor that impairs the repair of skin wounds is stress. In stressful situations (including situations in which wounds are likely to occur), the human body releases several chemicals that prepare the body for “fight or flight,” including cortisol and epinephrine (also called adrenaline). Most scientists ascribe the effects of stress on wound healing to stress-induced increases in cortisol, but might stress-induced epinephrine also affect wound healing? In this study, the researchers test whether epinephrine impairs keratinocyte migration and re-epithelialization of burn wounds (keratinocytes have a receptor for epinephrine called the β2 adrenergic receptor [β2AR] on their cell surface that allows them to respond to epinephrine). They chose to study burn wounds for two reasons. First, major burns cause a massive release of stress chemicals into the bloodstream that raises blood levels (systemic levels) of cortisol and epinephrine for days or weeks after the initial trauma. Second, despite recent therapeutic advances, many people still die from major burns (4,000 every year in the USA alone) so there is a pressing need for better ways to treat this type of wound.
What Did the Researchers Do and Find?
The researchers investigated the effects of epinephrine on wound healing in three types of experiments. First, they looked at the effect of epinephrine on keratinocytes growing in dishes (in vitro experiments). Levels of epinephrine similar to those in the blood of stressed individuals greatly inhibited the motility and migration of human keratinocytes (isolated from the foreskin of newborn babies) and of mouse keratinocytes. It also inhibited the repair of scratch wounds made in monolayers of keratinocytes growing on dishes. Treatment of the cultures with a β2AR antagonist (a chemical that prevents epinephrine activating the β2AR) reversed the effects of epinephrine. In addition, the migration of mouse keratinocytes that had been genetically altered so that they did not express β2AR was not inhibited by epinephrine. Next, the researchers investigated the healing of burn wounds made in small pieces of human skin growing in dishes (ex vivo experiments). Burn injuries rapidly increased the amount of epinephrine in these tissue explants, they report, and treatment of the explants with a βAR antagonist (an inhibitor of all types of βARs) greatly increased wound re-epithelialization. Finally, the researchers report that the re-epithelialization of burn wounds in living mice was improved when the mice were treated with a β2AR antagonist.
What Do These Findings Mean?
These findings reveal a second pathway by which stress can impair wound healing. They show that stress-induced increases in systemic and local epinephrine activate β2ARs on keratinocytes and that this activation inhibits keratinocyte motility and wound re-epithelialization. Although results obtained in animals do not always reflect what happens in people, the finding that the treatment of mice with β2AR antagonists improves the rate of burn wound re-epithelialization, suggests that beta blockers—drugs that inhibit all βARs and that are widely used to treat high blood pressure and to prevent heart disease—or specific β2AR antagonists might provide a new therapeutic approach to the treatment of burns and, perhaps, chronic nonhealing wounds.
Additional Information.
Please access these Web sites via the online version of this summary at
Wikipedia has pages on wound healing, burn injuries, and epinephrine (Note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The MedlinePlus Encyclopedia has a page on burns (in English and Spanish)
MedlinePlus provides links to other information on burns (in English and Spanish)
PMCID: PMC2621262  PMID: 19143471
7.  Association between Childhood Dental Experiences and Dental Fear among Dental, Psychology and Mathematics Undergraduates in Brazil 
The aim of the present study was to evaluate the association between childhood dental experiences and dental fear in adulthood among dentistry, psychology and mathematics undergraduate students. A cross-sectional study of 1,256 students from the city of Belo Horizonte, Brazil, was performed. Students responded to the Brazilian version of the Dental Fear Survey (DFS) and a questionnaire regarding previous dental experiences. Both the DFS and the questionnaire were self-administered. Association was tested using descriptive, bivariate and multivariate linear regression analysis, with a 5% significance level. Dentistry undergraduates reported lower scores than psychology (p < 0.001) and mathematics undergraduates (p < 0.05) for all three dimensions of the DFS. Negative dental experiences in childhood was associated with dimensions of Avoidance (B = 2.70, p < 0.001), Physiological arousal (B = 1.42, p < 0.001) and Fears of specific stimuli/situations (B = 3.44, p < 0.001). The reason for first visit to dentist was associated with dimensions of Physiological arousal (B = 0.76, p < 0.01) and Fears of specific stimuli/situations (B = 1.29, p < 0.01). Dentists should be encouraged to evaluate the dental fear of their patients before treatment. The DFS has been found to be an effective instrument for this purpose.
PMCID: PMC3546783  PMID: 23247225
dental fear; dental phobias; epidemiology; pediatric dentistry; questionnaires; behavior; undergraduate student
8.  Locoregional Anesthesia for Dental Treatment in Cardiac Patients: A Comparative Study of 2% Plain Lidocaine and 2% Lidocaine with Epinephrine (1:100,000) 
Clinics (Sao Paulo, Brazil)  2009;64(3):177-182.
This study analyzes hemodynamic changes in patients with cardiac valvular diseases submitted to dental treatment under local anesthesia containing epinephrine.
This randomized clinical trial was performed at the Dental Division of the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Brazil). Patients were separated into two groups with the help of an aleatory number table: 2% plain lidocaine (PL, n= 31) and 2% lidocaine with epinephrine (1:100,000) (LE, n= 28). Blood pressure, heart rate, oxygenation and electrocardiogram data were all recorded throughout the procedure. State and trait anxiety levels were measured.
Fifty-nine patients were selected for the LE group (n=28), with an average age of 40.3 ± 10.9, or for the PL group (n=31), age 42.2 ± 10.3. No differences were shown in blood pressure, heart rate and pulse oximetry values before, during and after local anesthesia injection between the two groups. State and trait anxiety levels were not different. Arrhythmias observed before dental anesthesia did not change in shape or magnitude after treatment. Complaints of pain during the dental procedure were more frequent within the PL group, which received a higher amount of local anesthesia.
Lidocaine with epinephrine (1:100,000) provided effective local anesthesia. This treatment did not cause an increase in heart rate or blood pressure and did not cause any arrhythmic changes in patients with cardiac valvular diseases.
PMCID: PMC2666461  PMID: 19330241
Anesthesia; Local; Lidocaine; Dental care; Arrhythmias; Cardiac; Anxiety
9.  Effects of local anesthesia of the cerebellum on classical fear conditioning in goldfish 
Besides the amygdala, of which emotion roles have been intensively studied, the cerebellum has also been demonstrated to play a critical role in simple classical fear conditioning in both mammals and fishes. In the present study, we examined the effect of local administration of the anesthetic agent lidocaine into the cerebellum on fear-related, classical heart-rate conditioning in goldfish.
The effects of microinjection of the anesthetic agent lidocaine into the cerebellum on fear conditioning were investigated in goldfish. The fear conditioning paradigm was delayed classical conditioning with light as a conditioned stimulus and electric shock as an unconditioned stimulus; cardiac deceleration (bradycardia) was the conditioned response.
Injecting lidocaine into the cerebellum had no effect on the base heart rate, an arousal/orienting response to the novel stimulus (i.e., the first presentation of light), or an unconditioned response to electric shock. However, lidocaine injection greatly impaired acquisition of conditioned bradycardia. Lidocaine injection 60 min before the start of the conditioning procedure showed no effect on acquisition of conditioned bradycardia, indicating that the effect of lidocaine was reversible.
The present results further confirm the idea that the cerebellum in teleost fish, as in mammals, is critically involved in classical fear conditioning.
PMCID: PMC2848191  PMID: 20331854
10.  Dental Fear among Medical and Dental Undergraduates 
The Scientific World Journal  2014;2014:747508.
Objective. To assess the prevalence and level of dental fear among health related undergraduates and to identify factors causing such fear using Kleinknecht's Dental Fear Survey (DFS) questionnaire. Methods. Kleinknecht's DFS questionnaire was used to assess dental fear and anxiety among the entire enrollment of the medical and dental undergraduates' of the University of Malaya. Results. Overall response rate was 82.2%. Dental students reported higher prevalence of dental fear (96.0% versus 90.4%). However, most of the fear encountered among dental students was in the low fear category as compared to their medical counterpart (69.2 versus 51.2%). Significantly more medical students cancelled dental appointment due to fear compared to dental students (P = 0.004). “Heart beats faster” and “muscle being tensed” were the top two physiological responses experienced by the respondents. “Drill” and “anesthetic needle” were the most fear provoking objects among respondents of both faculties. Conclusion. Dental fear and anxiety are a common problem encountered among medical and dental undergraduates who represent future health care professionals. Also, high level of dental fear and anxiety leads to the avoidance of the dental services.
PMCID: PMC4216710  PMID: 25386615
11.  Cardiovascular effect of epinephrine in endodontic microsurgery: a review 
Epinephrine is one of the most widely-used vasoconstrictors in dental treatment including endodontic microsurgery. However, the systemic safety of epinephrine has been in debate for many years because of its potential risk to cause cardiovascular complications. The purpose of this review was to assess the cardiovascular effect of epinephrine use in endodontic microsurgery. Endodontic microsurgery directly applies epinephrine into the bone cavity, and the amount is reported to be much larger than other dental surgeries. Moreover, when considering that systemic potency of intraosseous application is reported to be comparable to intravenous application, the systemic influence of epinephrine could be increased in endodontic microsurgery. Besides, pre-existing cardiovascular complications or drug interactions can enhance its systemic influence, resulting in increased susceptibility to cardiovascular complications. Although clinical studies have not reported significant complications for patients without severe systemic complications, many epinephrine-induced emergency cases are warning the cardiovascular risk related with pre-existing systemic disease or drug interactions. Epinephrine is a dose-sensitive drug, and its hypersensitivity reaction can be fatal to patients when it is related to cardiovascular complications. Therefore, clinicians should recognize the risk, and the usage of pre-operative patient evaluation, dose control and patient monitoring are required to ensure patient's safety during endodontic microsurgery.
PMCID: PMC3843028  PMID: 24303352
Cardiovascular diseases; Drug interactions; Endodontic microsurgery; Epinephrine; Hemostasis; Vasoconstrictor agents
12.  Plasma Epinephrine Levels and Cardiovascular Response to High Administered Doses of Epinephrine in Local Anesthesia 
Anesthesia Progress  1987;34(1):10-13.
The effects of administering an epinephrine-containing local anesthetic on plasma catecholamine levels and cardiovascular parameters were evaluated. Significant elevations were observed following administration of 8 dental cartridges of 2% lidocaine with epinephrine 1:100,000 (144 μg) throughout the 20 minute observation period, while minimal changes were observed in the patients who received 6 cartridges of 3% mepivicaine. One minute after injection, the mean plasma epinephrine level in the group receiving epinephrine was 27.5 times higher than baseline. Concurrent elevations in systolic pressure (15%), heart rate (33%), and the rate-pressure product (52%) were also observed. These results indicate that significant amounts of epinephrine can be systemically absorbed following intraoral injection and the absorbed epinephrine can alter the cardiovascular status of the patient.
PMCID: PMC2186227  PMID: 3472472
13.  Self-Reported Dental Fear among Dental Students and Their Patients 
The aim of the present study was to compare self-reported dental fear among dental students and patients at a School of Dentistry in Belo Horizonte, Brazil. Eighty students ranging in age from 20 to 29 years and 80 patients ranging in age from 18 to 65 years participated in the study. A self-administered pre-tested questionnaire consisting of 13 items was used for data acquisition. The city of Belo Horizonte Social Vulnerability Index (SVI) was employed for socioeconomic classification. The chi-square test and binary and multinomial logistic regression were employed in the statistical analysis, with the significance level set at 0.05. The majority of dental students (76.5%) sought the dentist for the first time for a routine exam, while patients (77.3%) mostly sought a dentist for the treatment of dental pain. Dental fear was more prevalent among the patients (72.5%) than the students (27.5%). A total of 47.1% of the students and 52.9% of the patients reported having had negative dental experiences in childhood. The logistic model revealed an association between dental fear and a pain-related experience (OR: 1.8; 95%CI: 1.3–2.6). Patients were more prone to dental fear (OR: 2.2; 95%CI: 1.0–5.0). Although at different percentages, both students and patients experienced dental fear. Current patient with previous experience of dental pain had more dental fear.
PMCID: PMC3315073  PMID: 22470277
behavior; fear; pain; undergraduate student; dentistry; epidemiology; health; patients
14.  Interactions between epinephrine, ascending vagal fibers, and central noradrenergic systems in modulating memory for emotionally arousing events 
It is well-established that exposure to emotionally laden events initiates secretion of the arousal-related hormone epinephrine in the periphery. These neuroendocrine changes and the subsequent increase in peripheral physiological output play an integral role in modulating brain systems involved in memory formation. The impermeability of the blood brain barrier to epinephrine represents an important obstacle in understanding how peripheral hormones initiate neurochemical changes in the brain that lead to effective memory formation. This obstacle necessitated the identity of a putative pathway capable of conveying physiological changes produced by epinephrine to limbic structures that incorporate arousal and affect related information into memory. A major theme of the proposed studies is that ascending fibers of the vagus nerve may represent such a mechanism. This hypothesis was tested by evaluating the contribution of ascending vagal fibers in modulating memory for responses learned under behavioral conditions that produce emotional arousal by manipulating appetitive stimuli. A combination of electrophysiological recording of vagal afferent fibers and in vivo microdialysis was employed in a second study to simultaneously assess how elevations in peripheral levels of epinephrine affect vagal nerve discharge and the subsequent potentiation of norepinephrine release in the basolateral amygdala. The final study used double immunohistochemistry labeling of c-fos and dopamine beta hydroxylase (DBH), the enzyme for norepinephrine synthesis to determine if epinephrine administration alone or stimulation of the vagus nerve at an intensity identical to that which improved memory in Experiment 1 produces similar patterns of neuronal activity in brain areas involved in processing memory for emotional events. Findings emerging from this collection of studies establish the importance of ascending fibers of the vagus nerve as an essential pathway for conveying the peripheral consequences of physiological arousal on brain systems that encode new information into memory storage.
PMCID: PMC3384987  PMID: 22754515
amygdala; emotional arousal; epinephrine; learning; memory; vagus nerve
15.  Comparison of anesthetic efficacy of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:80,000 epinephrine for inferior alveolar nerve block in patients with irreversible pulpitis 
Objectives: This study was done to compare the anesthetic efficacy of 4% articaine with 1:100,000 epinephrine with that of 2% lidocaine with 1:80,000 epinephrine during pulpectomy in patients with irreversible pulpitis for inferior alveolar nerve block in mandibular posterior teeth. Material and Methods: Patients with irreversible pulpitis referred to the Department of Conservative Dentistry and Endodontics, K.D. Dental College, randomly received a conventional inferior alveolar nerve block containing 1.8 mL of either 4% articaine with 1:100,000 epinephrine or 2% lidocaine with 1:80,000 epinephrine. After the patient’s subjective assessment of lip anesthesia, the absence/presence of pulpal anesthesia through electric pulp stimulation was recorded and the absence/presence of pain was recorded through visual analogue scale. Results: The pulpal anesthesia success for articaine (76%) was slightly more than with lidocaine (58%) as measured with pulp tester as well as for the pain reported during the procedure the success rate of articaine (88%) was slightly more than that of lidocaine (82%) although the difference between the two solutions was not statistically significant. Conclusions: Both the local anesthetic solutions had similar effects on patients with irreversible pulpitis when used for inferior alveolar nerve block.
Key words:Anesthesia, articaine, lignocaine, pulpitis.
PMCID: PMC4312679
16.  Nitrous Oxide and Occupational Exposure: It's Time to Stop Laughing 
Anesthesia Progress  1989;36(6):252-257.
Although nitrous oxide (N2O) has been widely used since 1844, in recent years it has been implicated in a number of serious health hazards such as reproductive, nerve, liver, and kidney disorders. The National Institute of Safety and Health (NIOSH) recommends a limit of 25 ppm for chronic exposure to N2O in the dental office. Our study monitored ambient N2O levels in the dental office. N2O levels were compared for procedures performed in open clinics and private operatories as well as with and without a gas-scavenging system. Measurements were taken in the Dental Breathing Zone (DBZ) and Dental Chair Foot (DCF) at regular intervals. A four- to eightfold increase in average N2O levels was noted in the DBZ for unscavenged versus scavenged procedures. A three- to fourfold increase for unscavenged versus scavenged procedures was similarly noted in the DCF. N2O were significantly higher in private operatories than in open clinics, due to limited room volumes and in the DBZ over the DCF, due to mask leakage and increased oral exhalation. Scavenged N2O levels for both operatory types did not meet NIOSH guidelines. In contrast to previous studies using any form of gas removal, our study shows a significant decrease in N2O level achieved with an adequate scavenger system. With only four states regulating the use of N2O, and with concern over its deleterious effects growing, additional states and the federal government are expected to enact legislation regulating the use of N2O in the near future.
PMCID: PMC2163978  PMID: 2490056
17.  An echocardiographic study of interactions between pindolol and epinephrine contained in a local anesthetic solution. 
Anesthesia Progress  1995;42(2):29-35.
An increasing number of dental patients are taking beta-adrenergic blockers for the treatment of hypertension or angina pectoris. If epinephrine-containing local anesthetics are administered to such patients, interactions between epinephrine and the beta-blocking agent may induce cardiovascular complications. We assessed in volunteers the effects of intraoral injection with 2% lidocaine containing 1:80,000 epinephrine (L-E) on cardiac function after pretreatment with the beta-blocking agent pindolol. M-Mode echocardiography was used for the assessment. The injection of L-E after administration of pindolol did not alter cardiac preload, whereas it reduced the stroke volume, due to an increase in afterload and a decrease in myocardial contractility. Reductions in stroke volume and heart rate led to a decrease in cardiac output. Because total peripheral vascular resistance increased markedly, blood pressure was elevated despite the reduced cardiac output. These results suggest that cardiac function of dental patients on beta-blocker therapy can be adversely affected by epinephrine-containing local anesthetics. Therefore, when such an anesthetic solution has to be used in patients on beta-blocker therapy, careful systemic monitoring is needed.
PMCID: PMC2148851  PMID: 8934951
18.  Dental Fear and Concomitant Factors in 3-6 Year-old Children 
Background and aims
Dental fear/anxiety as a barrier in accessing oral health care is poorly investigated in Iranian children. The aims of this study were to evaluate the prevalence of dental fear and behavior management problems, as well as to examine the relationship between dental fear/anxiety and probable concomitant factors.
Materials and methods
Mothers of 200 children aged 3-6 were participated in this descriptive-analytic study, and completed the CFSS-DS, SDQ, Chora and Spielberger questionnaires for both child and parents’ general and dental anxiety in this descriptive- analytic study. Behavior was evaluated according to Frankl scale. Statistical approaches included T-test, chi-sq, and Pearson Linear correlation.
The mean score of dental fear was 32.15 ± 10 and the prevalence was 22.2%. Significant correlations were found between child’s dental fear, general fear and behavior management problems; however, no relationship was found between child’s dental fear and parental dental or general fear.
According to results of this study dental fear/anxiety seems to be more conditional and related to child’s temperament than parental impact. Parental evaluation of dental fear can be used as a predictor of child’s dental behavior.
PMCID: PMC3445318  PMID: 22991640
Behavior management; child; dental fear and anxiety; general anxiety
19.  Quantitative analysis of bacterial aerosols in two different dental clinic environments. 
Microbial aerosols are generated during dental treatments and may represent an important source of infection. This study was designed to quantify bacterial air contamination during dental treatments in both a closed dental operatory and a multichair dental clinic. Air was sampled by using a slit type of biological air sampler. Following air sampling, blood-supplemented Trypticase soy agar plates were incubated at 37 degrees C under anaerobic conditions for 7 days. The maximum levels of air contamination in the closed dental operatory were observed while dental treatments were being performed (four trials; 216 +/- 75 CFU/m3 for ultrasonic scaling treatments and 75 +/- 22 CFU/m3 for operative treatments). At 2 h after completion of the treatments, the bacterial counts were about the same as the pretreatment levels (12 to 14 CFU/m3). In the second part of the study, a multichair dental clinic was divided into four areas, and air contamination was monitored at each site. Three sites were located in active dental treatment areas, whereas no dental treatments were performed within an 11-m radius of the fourth site. At 3 h after the beginning of dental treatments, the highest bacterial counts were obtained in the three active dental treatment areas (76 to 114 CFU/m3). However, there was noticeable contamination in the inactive dental treatment area (42 CFU/m3). Thus, bacterial aerosols were able to spread into areas where there was no dental activity. My data show that dental treatments significantly increased the levels of bacterial air contamination in both a closed dental operatory and a multichair dental clinic.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC167591  PMID: 7487047
20.  Perceiving Control Over Aversive and Fearful Events Can Alter How We Experience Those Events: An Investigation of Time Perception in Spider-Fearful Individuals 
We used a time perception task to study the effects of the subjective experience of control on emotion and cognitive processing. This task is uniquely sensitive to the emotionality of the stimuli: high-arousing negative stimuli are perceived as lasting longer than high-arousing positive events, while the opposite pattern is observed for low-arousing stimuli. We evaluated the temporal distortions of emotionally charged events in non-anxious (Experiments 1 and 5) and spider-fearful individuals (Experiments 2–4). Participants were shown images of varying durations between 400 and 1600 ms and were asked to report if the perceived duration of the image seemed closer to a short (400 ms) or to a long (1600 ms) standard duration. Our results replicate previous findings showing that the emotional content of the image modulated the perceived duration of that image. More importantly, we studied whether giving participants the illusion that they have some control over the emotional content of the images could eliminate this temporal distortion. Results confirmed this hypothesis, even though our participant population was composed of highly reactive emotional individuals (spider-fearful) facing fear-related images (spiders). Further, we also showed that under conditions of little-to-no control, spider-fearful individuals perceive temporal distortions in a distinct manner from non-anxious participants: the duration of events was entirely determined by the valence of the events, rather than by the typical valence × arousal interaction. That is, spider-fearful participants perceived negative events as lasting longer than positive events, regardless of their level of arousal. Finally, we also showed that under conditions of cognitive dissonance, control can eliminate temporal distortions of low arousal events, but not of high-arousing events, providing an important boundary condition to the otherwise positive effects of control on time estimation.
PMCID: PMC3444055  PMID: 23060824
feeling of control; time perception; spider-fearful; emotion and cognition; emotion regulation
21.  Dental fear among university students: implications for pharmacological research. 
Anesthesia Progress  1998;45(2):62-67.
University students are often subjects in randomized clinical trials involving anxiolytic and analgesic medications used during clinical dental and medical procedures. The purpose of this study was to describe a typical university student population available for research by using data from a mail survey. Subjects were 350 students chosen randomly from all enrolled, full-time, traditional students on the main campus at the University of Washington in Seattle, WA. The aim was to determine the extent and nature of dental anxiety in this population. In addition, the relationships between subject willingness to receive dental injections and general and mental health and medical avoidance and medical fears were examined. The Dental Anxiety Scale (DAS) was used to measure dental anxiety. Dental anxiety was prevalent in this population; 19% of students reported high rates of dental fear. Thirteen percent of students had never had a dental injection. Students with no experience with dental injections were more reluctant than those with experience to receive an injection if one were needed. DAS scores were correlated with injection reluctance. Students who were reluctant to go ahead with a dental injection also reported poorer general and mental health than those who were less reluctant. These students also reported higher medical avoidance and medical anxiety scores. University students provide a rich source of potential subjects for clinical research. The student population, like the community at large, contains people with high levels of dental and medical fear.
PMCID: PMC2148972  PMID: 10356434
22.  Dental subscale of children's fear survey schedule and dental caries prevalence 
European Journal of Dentistry  2013;7(2):181-185.
To assess the level of fear of dental procedures among 6-12 year school children and correlate the prevalence of dental caries with their dental fears scores.
Materials and Methods:
The study sample of 444 school children, comprising of 224 girls and 220 boys in the age group of 6-12 years old from a private English medium school were selected. Each student was asked to independently complete a Children's Fear Survey Schedule – Dental Subscale (CFSS-DS) questionnaire. Children having a score of ≥ 38 were included in the “dental fear” group while those scoring <38 were placed in the “without dental fear” group. All dental examinations were performed in the classroom.
Fear scores were highest for “Injections,” (3.76 ± 0.68) “Choking,” (3.48 ± 0.63) and “Dentist drilling” (2.88 ± 0.69). The overall mean score of CFSS-DS in our study was 37.0 ± 8.89, mean score of DMFT and DMFS were 0.58 ± 0.74 and 0.73 ± 1.09, respectively. Mean score of deft and defs were 4.40 ± 2.34 and 7.28 ± 5.49, respectively.
The study showed the prevalence of dental fear in 6-12 year old children and there was no statistically significant co-relation between the level of dental fear and dental caries in these children.
PMCID: PMC4023184  PMID: 24883023
Children; dental caries; dental fear; prevalence
23.  A Comparative Study of Lidocaine and Lidocaine­ Mannitol in Anesthetizing Human Teeth with Inflamed Pulps 
Iranian Endodontic Journal  2006;1(1):19-23.
INTRODUCTION: Failure to achieve adequate and profound anesthesia in teeth with acute pulp inflammation is a common condition during emergency visits in root canal therapy. Many different anesthetic solutions such as morphine and capsaicin have accordingly been examined. Mannitol­ an alcoholic sugar with high osmotic pressure level- is applicated for reducing intracranial and post retinal pressure in medicine. It has also been used for its diuretic effect. In combination with local anesthetic solution, it increases permeability of the nerve fiber sheath and leads to influx of the local anesthetic through cytoplasmic membrane .The purpose of the present study was to compare the efficacy of routine local anesthesia with or without using mannitol in teeth with inflamed pulps.
MATERIALS AND METHODS: one hundred patients with acute dental pain in posterior teeth were selected. Vials with 3 ml anesthetic solution containing 2.5% lidocaine with 1/80000 epinephrine or 2.5% lidocaine with 1/80000 epinephrine and 0.5 mol mannitol were used for anesthesia. For each patient, the routine injection technique was applied, during the removal of decay and dentine. Depth of anesthesia was evaluated and the supplementary injection was done in case of pain feeling and then pulpotomy was done. The analysis of data was done using chi-square statistical test.
RESULTS: The results showed that complete anesthesia after the first injection was obtained with lidocaine mannitol in 46% and with lidocaine alone in 38% of cases. However, the difference was not significant.
CONCLUSION: These finding suggest that the addition of mannitol to the standard anesthetic solution could insignificantly increase the level of anesthesia in teeth with inflamed pulps.
PMCID: PMC3909611  PMID: 24494021
Anesthesia; Lidocaine; Mannitol
24.  Mechanisms of postprandial glucose counterregulation in man. Physiologic roles of glucagon and epinephrine vis-a-vis insulin in the prevention of hypoglycemia late after glucose ingestion. 
Journal of Clinical Investigation  1983;72(1):278-286.
The transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is not solely attributable to dissipation of insulin and, therefore, must also involve factors that actively raise the plasma glucose concentration--glucose counterregulatory factors. We have shown that the secretion of two of these, glucagon and epinephrine, is specific for glucose ingestion and temporally related to the glucose counterregulatory process. To determine the physiologic roles of glucagon and epinephrine in postprandial glucose counterregulation, we produced pharmacologic interventions that resulted in endogenous glucagon deficiency with and without exogenous glucagon replacement, adrenergic blockade, and adrenergic blockade coupled with glucagon deficiency starting 225 min after the ingestion of 75 g of glucose in normal subjects. Also, we assessed the effect of endogenous epinephrine deficiency alone and in combination with glucagon deficiency late after glucose ingestion in bilaterally adrenalectomized subjects. Glucagon deficiency resulted in nadir plasma glucose concentrations that were approximately 30% lower (P less than 0.01) than control values, but did not cause hypoglycemia late after glucose ingestion. This effect was prevented by glucagon replacement. Neither adrenergic blockade nor epinephrine deficiency alone impaired the glucose counterregulatory process. However, combined glucagon and epinephrine deficiencies resulted in a progressive fall in mean plasma glucose to a hypoglycemic level late after glucose ingestion; the final glucose concentration was 40% lower (P less than 0.02) than the control (epinephrine deficient) value in these patients, and was nearly 50% lower (P less than 0.001) than the control value and approximately 30% lower (P less than 0.05) than the glucagon-deficient value in normal subjects. We conclude (a) the transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is the result of the coordinated diminution of insulin secretion and the resumption of glucagon secretion. (b) Epinephrine does not normally play a critical role in this process, but enhanced epinephrine secretion compensates largely and prevents hypoglycemia when glucagon secretion is deficient.
PMCID: PMC1129183  PMID: 6135707
25.  Behavioral and Perceived Stressor Effects on Urinary Catecholamine Excretion in Adult Samoans 
The effects of perceptions and behaviors related to culturally-patterned socioeconomic obligations on catecholamine excretion rates were studied in a cross-sectional sample of Samoan adults.
378 participants, ages 29-62 years, from 9 villages throughout Samoa, provided timed overnight urine specimens, and self-reported perceptions and behaviors associated with contributions to one's family, aiga, and chief, matai, and communal gift exchanges, fa'alavelave. Urinary norepinephrine and epinephrine excretion rates were measured by high performance liquid chromatography with electrochemical detection. Age (≤40 vs. >40 years) and gender-specific regression models were estimated to detect associations with catecholamine excretion.
Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who view their contribution to their matai to be ‘just right’, had significantly higher residence-adjusted norepinephrine excretion. Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who consider their contribution to their aiga not to be a burden, had higher epinephrine excretion. Older men who contribute more to their aiga and who perceive their contribution to their aiga to be ‘just right’ had increased residence-adjusted epinephrine excretion.
Individual-level perceptions and behaviors related to traditional socioeconomic obligations are a significant correlate of increased overnight catecholamine excretion rates. Higher excretion rates may be attributed to psychosocial stress arousal associated with a discordance between personal desires for upward social mobility, and family and community-based socioeconomic obligations. Changes in patterns of individual-level psychosocial stress arousal may contribute to cardiovascular disease risk in modernizing Samoans.
PMCID: PMC3152635  PMID: 21793091
Epinephrine; norepinephrine; Samoans; psychosocial stress

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