When toothache results in asthma diagnosis.

Local anesthetics (LA) have been used for a wide variety of procedures over the years due to their analgesic effect. These drugs have been seen to cause adverse events in the pediatric population, but an actual allergy must be in question. A case of an apparent hypersensitivity reaction to LA used in the setting of dental procedures in a 14.5-year-old girl with a forgotten history of asthma was reported and medical documentation review was performed. After treatment with LA during several dental procedures, the patient presented the shortness of breath, malaise and fainting, which then resolved spontaneously. After proper history taking, and skin and provocation tests, the patient was diagnosed with bronchial asthma and emotional sensitivity. The patient's recommendation included using an antihistamine and controlling her asthma before the use of LA, and administering the drug in a supine position. It is essential to consider all possible etiologies of an adverse event after using drugs in the pediatric population and to perform proper testing before making the diagnosis of a drug allergy.

Mode of delivery alters dental pulp nociception and pain-induced changes in cognitive performance in adults male rats.

This study examined the effects of delivery mode on the response to inflammatory pulpal pain and pain-induced changes in cognitive performance in adult rats. Experiments were done on rats born by vaginal or caesarean section (C-section) delivery. Dental pulp was irritated by intradental capsaicin (100 µg) application and then nociceptive scores were recorded for 40 min. Spatial and passive avoidance learning and memory were assessed using the Morris water maze (MWM) and shuttle box tools, respectively. Additionally, in vivo recording of field excitatory postsynaptic potential (fEPSP) in the CA1 of the hippocampus was used to verify synaptic plasticity. Capsaicin produced more significant nociceptive behavior in vaginally delivered rats compared to C-section rats (P < 0.01). C-section-delivered rats show better performance in both MWM and shuttle box tests. Likewise, C-section rats had greater fEPSP slopes compared to the vaginally delivered group (P < 0.05). Capsaicin impairs cognitive performance in rats born by each delivery route. However, capsaicin effects were more significant in rats delivered vaginally than by C-section. Overall, C-section-delivered rats show lower sensitivity to capsaicin-evoked pulpal nociception and better cognitive performance than vaginally delivered rats. These effects are in part mediated by reduced neuroinflammation and enhanced neuronal synaptic plasticity following C-section delivery.

Salivary opiorphin in dental pain: A potential biomarker for dental disease.

OBJECTIVES: Opiorphin is a recently discovered peptide shown to inhibit the enkephalin-degrading enzymes and prolong the effects of enkephalins. Although opiorphin is found in high concentrations in saliva, the relationship between salivary opiorphin and orofacial pains is not yet fully understood. We aimed to determine salivary opiorphin concentrations in dental pain related to symptomatic irreversible pulpitis (SIP), and symptomatic apical periodontitis (SAP). DESIGN: 39 patients participated in this study. The participants were categorized into SIP and SAP based on their diagnosis. All the patients were treated with root canal treatment. Saliva specimens were collected, and pain levels were recorded at pre-treatment, 7 days post-treatment and 30 days post-treatment. Saliva opiorphin levels were measured using a commercially available ELISA kit. Pre-treatment and post-treatment opiorphin levels were evaluated using repeated measures ANOVA. Correlations between VAS scores, opiorphin levels and age were evaluated using Spearman's Rank Correlation. RESULTS: The average saliva opiorphin level pre-treatment, 7 days post-treatment and 30 days post-treatment were 31.28 ± 7.10 ng/ml, 20.41 ± 2.67 ng/ml and 18.61 ± 2.05 ng/ml respectively. Significantly higher pre-treatment opiorphin levels were observed in the SIP group compared to the SAP group. A strong correlation was observed between the pre-treatment pain levels and the saliva opiorphin concentrations. CONCLUSIONS: Our findings indicate that saliva opiorphin levels increase in inflammation related dental pain. The level of salivary opiorphin is strongly correlated with the reported level of pain. The extent of the inflammation (pulpal vs. periodontal) also affects the opiorphin level.

Activation of trigeminal ganglion satellite glial cells in CFA-induced tooth pulp pain in rats.

This study further investigated the mechanisms underlying the rat model of tooth pulp inflammatory pain elicited by complete Freund's adjuvant (CFA), in comparison to other pulpitis models. Pulps of the left maxillary first molars were accessed. In the CFA group, the pulps were exposed, and CFA application was followed by dental sealing. In the open group, the pulps were left exposed to the oral cavity. For the closed group, the pulps were exposed, and the teeth were immediately sealed. Naïve rats were used as negative controls. Several parameters were evaluated at 1, 2, 3 and 8 days. There was no statistical significant difference among the groups when body weight variation, food or water consumption were compared. Analysis of serum cytokines (IL-1ß, TNF or IL-6) or differential blood cell counts did not reveal any evidence of systemic inflammation. The CFA group displayed a significant reduction in the locomotor activity (at 1 and 3 days), associated with an increased activation of satellite glial cells in the ipsilateral trigeminal ganglion (TG; for up to 8 days). Amygdala astrocyte activation was unaffected in any experimental groups. We provide novel evidence indicating that CFA-induced pulp inflammation impaired the locomotor activity, with persistent activation of ipsilateral TG satellite cells surrounding sensory neurons, without any evidence of systemic inflammation or amygdala astrogliosis.

Tooth whitening with hydrogen peroxide in adolescents: study protocol for a randomized controlled trial.

BACKGROUND: Technological innovations in dental materials have been fueled by the desire of patients to improve the esthetics of their teeth. This emphasis on esthetics has led dentists to seek resources that respect the standards established by society, but without compromising the integrity of the teeth. METHODS/DESIGN: The aim of the proposed controlled clinical trial will be to assess colorimetric changes and increased dental sensitivity in adolescent patients submitted to tooth whitening with 6% and 7.5% hydrogen peroxide using home kits with whitening strips. Adolescents aged 12 to 20 years will be allocated to different groups based on treatment (n = 16 per group): (1) placebo; (2) 6.0% hydrogen peroxide (White Class with Calcium, FGM); (3) 7.5% hydrogen peroxide (White Class with Calcium, FGM); and (4) 7.5% hydrogen peroxide (Oral B 3D White, Oral-B). After the whitening procedures, the participants will be evaluated using a visual analog scale for tooth sensitivity and digital spectrophotometry to measure changes in color. Descriptive analysis of the data will be performed. Either the chi-squared test or Fisher's exact test will be used for the determination of associations among the categorical variables. Student's t-test and analysis of variance will be used to compare mean colorimetric data. Pearson's correlation coefficients will be calculated to determine the strength of correlations among the continuous variables. DISCUSSION: This randomized trial will provide an opportunity to evaluate products such as whitening strips in comparison to other self-administered methods, especially in adolescents. TRIAL REGISTRATION: The protocol for this study was submitted to Clinical Trials in November 2013 with registration number NCT01998386.

Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model.

Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states.

The role of N-methyl-D-aspartate receptor subunits in the rat thalamic mediodorsal nucleus during central sensitization.

We have identified tooth pulp-driven neurons (TPDNs) in the thalamic mediodorsal nucleus (MD) in rats and showed that the TPDNs' responsiveness in the MD is increased by chemical conditioning stimulation of allyl-isothiocyanate (mustard oil) to the molar tooth pulp. The aim of the present study was to address the role of N-methyl-d-aspartate receptors (NMDA receptors) in the sensitized central nervous system following the mustard oil application to the rat tooth pulp. Microinjection of MK-801, a noncompetitive NMDA receptor antagonist, to the thalamic MD nucleus reduced the TPDNs' responsiveness in the thalamic MD nucleus. Gene expression analysis showed that expression levels of NMDA receptor subunits NR2A and NR2D mRNAs in the thalamus were increased by the mustard oil application and that the increases were reduced by MK-801. When naloxone, an opioid receptor antagonist, was given systemically following the MK801 microinjection, the TPDNs' responsiveness was rekindled and expression levels of NR2D and NR2A mRNAs were increased. Moreover, lidocaine pretreatment abolished the mustard oil-induced upregulation of NR2D and NR2A mRNAs. These results suggest that, during central sensitization, interaction of NMDA receptors and endogeneous opioid-related inhibitory mechanisms plays critical role in the alteration of the TPDNs' responsiveness in the thalamic MD nucleus.

Cytotoxic chemotherapy-induced odontalgia: a differential diagnosis for dental pain.

INTRODUCTION: Peripheral neurotoxicity and neuropathic pain are well-known complications of several anti-cancer chemotherapeutic agents. Such pain might cause an impairment of the patient's quality of life and is a common limiting factor of anti-cancer chemotherapy. Neurotoxicity in orofacial structures has been previously described as diffuse jaw pain or numbness. Currently, localized pulpal pain is not listed as a possible complication of cytotoxic therapy. The aim of this report was to suggest cytotoxic-induced neurotoxicity as a differential diagnosis for toothache during anti-cancer therapy. METHODS: We described the diagnostic process in a patient suffering from severe pulpal pain in apparently intact teeth during cytotoxic therapy. A non-Hodgkin's lymphoma patient complained of 2 episodes of excruciating dental pain evoked by mouth breathing, which caused nocturnal awakenings. RESULTS: Both episodes developed immediately after administrations of cyclophosphamide as part of an anti-cancer chemotherapy protocol. Clinical parameters and radiographic characteristics eliminated other possible dental and facial etiologies. Pulp extirpation (pulpectomy) resulted in immediate pain relief. In both episodes, cytologic evaluation of the extirpated pulp tissue failed to show inflammation or an infiltration of lymphoma cells. CONCLUSIONS: This case presented a circumstantial relation between the clinical presentation of dental pain, with associated significant impairment of the patient's quality of life, and the timing of administrations of high-dose cyclophosphamide. It suggests that chemotherapy-induced toxicity might manifest as pulpitis-like toothache, which might present a diagnostic challenge for the dental practitioner.

Arsenic trioxide associated toothache.

Arsenic trioxide in the treatment of acute promyelocytic leukaemia is relatively safe with minimal side effects. Dental toxicities associated with its use are uncommon. We describe the first case report of toothache associated with arsenic trioxide. A 45-year-old male with relapsed APL was commenced on a treatment schedule of all-trans-retinoic acid 20mg four times a day for 14 days concurrent with a 10mg intravenous infusion of arsenic trioxide for 28 days. After 14 doses of the 6th cycle of treatment he experienced severe acute pain in various parts of the oral cavity. Extensive examination including an orthodontic review concluded there was no indication that the pain symptoms were due to a dental or endodontic cause. Four days after completing his 6th cycle the pain completely resolved. The mechanism of this adverse event remains unclear. Physicians with patients receiving arsenic trioxide with unexplained toothache should consider the arsenic as the cause of the pain.

A clinical evaluation of two in-office bleaching regimens with and without tray bleaching.

This study evaluated the degree of color change of teeth, the rebound effect and the sensitivities of teeth and gingiva associated with the use of an in-office bleaching agent followed by an at-home bleaching agent to lighten stained teeth in an in vivo study. Thirty-seven subjects who met the Inclusion/Exclusion criteria were divided into two cells. Twenty-five subjects received three 15-minute in-office bleaching treatments in succession with 36% hydrogen peroxide (HP) on the maxillary anterior teeth, followed by at-home overnight bleaching with 15% carbamide peroxide (CP) for seven days on one side of the dental arch. Twelve other subjects received a 40-minute in-office bleaching treatment on their maxillary anterior teeth, followed by at-home overnight bleaching for seven days on one side of the dental arch with the same product. The cells of teeth on the other side of the dental arch received the same in-office treatment but were not bleached overnight for seven days. Color was subjectively evaluated using the Vitapan Classical Shade Guide and was objectively evaluated using the Chroma Meter at the baseline appointment, immediately after in-office bleaching and at 4, 7 and 14 days and 3 months after the in-office treatment. For two weeks, the subjects completed sensitivity evaluations of gingival tissues and hard tooth tissues. The cells that did not receive the at-home bleaching had significantly less color change than the cells that received at-home bleaching. The cell that was bleached for 40 minutes and received the at-home treatment had significantly less overall change (deltaE) at 14 days and 3 months than the cell that received three 15-minute treatments with the at-home treatment. Throughout the study, the subjects in the three 15-minute treatment cells had less gingival and tooth sensitivity than the other cells.

Blink reflexes in patients with atypical odontalgia.

AIMS: To use the human blink reflex (BR) to explore possible neuropathic pain mechanisms in patients with atypical odontalgia (AO). METHODS: In 13 AO patients, the BR was elicited using a concentric electrode and recorded bilaterally with surface electromyographic (EMG) electrodes on both orbicularis oculi muscles. Electrical stimuli were applied to the skin above branches of the V1, V2, and V3 nerves and to the V branch contralateral to the painful branch. Sensory and pain thresholds were determined. The BR examination of the painful V branch was repeated during a capsaicin pain-provocation test. The data were analyzed with nonparametric statistics. RESULTS: The BR responses (R2 and R3) evoked by stimulation of V3 were significantly smaller than the BR responses evoked by stimulation of V1 and V2 (P < .004). There were no differences in BR (R2 or R3) between the painful and nonpainful sides (P > .569), and the BR (R2 and R3) was not significantly modulated by experimental pain (P > .080). The sensory thresholds were significantly lower on the painful side compared to the nonpainful side (P = .014). The pain thresholds were not different between sides (P > .910). CONCLUSION: No major differences between the V nociceptive pathways on the right and left sides were found in a relatively small group of AO patients. Future studies that compare BRs in AO patients and healthy volunteers are needed to provide further knowledge on the pain mechanisms in AO.

Drug-induced disorders of teeth.

It is essential that every health care professional who is involved with the prescription or recommendation of drugs be fully aware of any resultant disorders that may arise as a side-effect. A range of drugs can affect the teeth. In this review article, drugs that have the potential to induce changes in teeth have been classified as those leading to tooth discoloration (intrinsic and extrinsic), physical damage to tooth structure (enamel, dentin, and cementum), and alteration in tooth sensitivity.

Three-week clinical trial of a 14% hydrogen-peroxide, strip-based bleaching system.

This clinical trial tested the efficacy and safety of a professional strip-based whitening system (Crest Whitestrips Supreme) using the manufacturer's recommended 3-week treatment regimen. These strips have a higher concentration, but a similar amount of hydrogen peroxide relative to Crest Professional Whitestrips, because the thickness of the gel on strips is reduced. Tooth whitening was measured using the value-oriented VITA Classic Shade Guide before and after treatment. Twenty-nine subjects were treated with either Crest Whitestrips Supreme or placebo strips that did not contain hydrogen peroxide. Participants in the experimental group achieved a mean lightening of nearly eight VITA shades relative to placebo, with minimal side effects.

Placebo-controlled, 6-week clinical trial on the safety and efficacy of a low-gel, 14% hydrogen-peroxide whitening strip.

Clinical research was conducted to evaluate the extended-use safety and efficacy of Crest Whitestrips Supreme, a low-gel (100 mg on maxillary strip), 14% hydrogen-peroxide professional tooth-whitening system. The parallel-group study was randomized, double-blind, and placebo-controlled, and involved 39 healthy adults. During the treatment phase, subjects used the investigational products twice daily (for 30 minutes each) for 6 weeks (42 days). Safety and efficacy measurements were obtained at baseline and at the completion of each 3-week treatment period. Results showed that twice-daily use of Crest Whitestrips Supreme for 3 weeks resulted in a highly significant (P < .0001) improvement in tooth color, with a mean yellowness reduction (delta b*) of -3.3 and a mean brightness improvement (delta L*) of 2.4 relative to placebo. Color improvement continued with extended strip use over 6 weeks for all parameters (P < .0005). Relative to placebo at 6 weeks, color improvement was highly significant (P < .0001), with a mean delta b* of -4.1 and a mean delta L* of 3.2. Mild and transient tooth sensitivity and oral irritation were the most common adverse events. There was no evidence of any meaningful increase in adverse events with extended treatment through 6 weeks. Twice-daily use of Crest Whitestrips Supreme resulted in a highly significant improvement in tooth color after 3 weeks, with color improvement continuing over 6 weeks.

Clinical trial comparing two daytime hydrogen-peroxide professional vital-bleaching systems.

A randomized clinical trial was conducted to compare the whitening effectiveness and tolerability of two daytime, professional, hydrogen-peroxide, vital-bleaching systems. Adults who had never bleached their teeth were randomly assigned to use either 14% hydrogen-peroxide whitening strips or a marketed 9.5% hydrogen-peroxide custom-tray-based system. Maxillary arch treatment was twice daily for 30 minutes for 9 to 21 days, depending on the labeled instructions for use. Whitening response was measured objectively as L*a*b* (which represent three-dimensional tooth color from light to dark, green to red, and blue to yellow, respectively) from digital images of the maxillary anterior teeth, while comparative at-home tolerability was assessed from bleaching tolerability severity days (BTSD) scores. A total of 31 participants aged 18 to 64 were evaluated. At the end of treatment, the adjusted mean (standard deviation [SD]) delta b* was -3.35 (0.37) for the strips and -1.67 (0.344) for the trays. Treatments differed significantly (P < .05) with respect to delta b*, as well as to delta L* and delta W* values at the end of treatment. Overall, at-home strip use was better tolerated, especially with respect to oral irritation. BTSD means (SD) were 0.09 (0.25) and 0.38 (0.49), with treatments differing significantly (P = .036), favoring the strips. This comparative research demonstrated that at the end of treatment, the 14% hydrogen-peroxide whitening strips resulted in a superior, twofold reduction in yellowness and better in-use tolerability compared to the 9.5% hydrogen-peroxide custom-tray system.

Clinical comparison of two self-directed bleaching systems.

PURPOSE: This randomized clinical trial compared the clinical efficacy and tolerability of 2 marketed self-directed vital tooth-whitening systems. MATERIALS AND METHODS: Balancing for baseline tooth color, self-reported coffee/tea use, and age, 57 adult volunteers were randomized to either a whitening strip containing 6% hydrogen peroxide or a tray-based 10% carbamide peroxide/dentifrice/mouth rinse combination system. Following the manufacturer's directions, the strip group bleached twice daily for 30 minutes, whereas the tray group bleached twice daily for 20-30 minutes, preceded by tooth brushing with a whitening dentifrice and followed by mouth rinsing with a whitening solution. Treatment extended for 14 days, with evaluation at day 7 and again at day 14. Whitening response was measured objectively as L*a*b* from standardized digital images of maxillary anterior teeth. Tolerability was assessed by oral examination and subject interview. Efficacy comparisons were made using analysis of covariance, whereas tolerability was compared using the nonparametric Wilcoxon rank-sum test. RESULTS: Both treatments resulted in statistically significant (P < 0.01) improvements from baseline for all color parameters. For between-group comparisons, the 6% hydrogen peroxide strips yielded a nearly 3-fold reduction in yellowness (deltab*), a nearly 2-fold improvement in lightness (deltaL*), 2.6 times greater redness reduction (deltaa*), and a more than 2-fold change in overall color (deltaE*) compared to the tray-based combination system. Between-group comparisons were statistically significant for the all color parameters at both the day 7 and day 14 evaluations (P < 0.001). In general, 7-day use of the whitening strips provided significantly greater color improvement relative to the combination dentifrice/gel/rinse system at day 14. In addition, the groups differed significantly (P < 0.05) in bleaching tolerability severity-days, with the strip system demonstrating better overall tolerability compared to the combination system. CONCLUSIONS: The single-step 6% hydrogen peroxide strips demonstrated better overall clinical response, in terms of both tooth-whitening efficacy and tolerability, than the multiple-step tray-based combination system.

Nociceptive behaviour induced by dental application of irritants to rat incisors: a new model for tooth inflammatory pain.

Animal models simulating acute human pulpitis are still lacking. The rat incisors present a particular situation where most of their innervation is considered to be unmyelinated and concentrated mainly in the tooth pulp. This study reports on a new model for dental pain induced by inflammatory agents applied to the tooth pulps of incisors. In different groups of rats, artificial crowns were fixed on the lower incisors, after cutting 1-2mm of their distal extremities. A volume of 7-10 microl of solutions of saline, capsaicin (1-10mg/ml) or formalin (2.5% or 5%) was injected in the crown cavity, and the nociceptive behaviour was quantitated following a devised scoring method of four scales. Intradental application of capsaicin produced nociceptive scores in the form of one plateau for 1-2h depending on the concentration used. Similar results were obtained with intradental application of formalin 2.5%. The one plateau of nociceptive scores obtained with formalin contrasts with the biphasic aspect of nociceptive behaviour described with the intradermal formalin test. This discrepancy could be attributed to a difference in the types of afferent fibres involved in each situation. Pretreatment with morphine (2 mg/kg) attenuated, in a naloxone-reversible manner, the nociceptive behaviour observed following intradental application of capsaicin. Pretreatment with meloxicam (a cyclo-oxygenase-2 inhibitor) exerted a less pronounced attenuation of the nociceptive scores when compared with morphine. These results provide evidence for the validity of the described model for the simulation of tooth pulp inflammatory pain in awake animals.

Neuroplasticity induced by tooth pulp stimulation in trigeminal subnucleus oralis involves NMDA receptor mechanisms.

We have recently demonstrated that application of the mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant increases in jaw muscle electromyographic (EMG) activity and neuroplastic changes in trigeminal (V) subnucleus caudalis. Since subnucleus oralis (Vo) as well as caudalis receives projections from molar pulp afferents and is also an integral brain stem relay of afferent input from orofacial structures, we tested whether MO application to the exposed pulp induces neuroplastic changes in oralis neurons and whether microinjection of MK-801, a noncompetitive NMDA antagonist, into the Vo influences the pulp/MO-induced neuroplastic changes in chloralose/urethan-anesthetized rats. Single neuronal activity was recorded in Vo, and neurons classified as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), deep (D), or skin/mucosa and deep (S + D). The spontaneous activity, mechanoreceptive field (RF) size, mechanical threshold, and response to suprathreshold mechanical stimuli applied to the neuronal RF were assessed prior to and throughout a 40- to 60-min period after MO application to the maxillary molar pulp. In animals pretreated with saline microinjection (0.3 microl) into the Vo, MO application to the pulp produced a significant increase in spontaneous activity, expansion of the pinch or deep RF, decrease in the mechanical threshold, and increase in response to suprathreshold mechanical stimuli of the nociceptive (WDR, NS, and S + D) neurons except for those nociceptive neurons having their RF only in the intraoral region. The pulpal application of MO did not produce any significant neuroplastic changes in LTM neurons. Furthermore, in animals pretreated with MK-801 microinjection (3 microg/0.3 microl) into the Vo, MO application to the pulp did not produce any significant changes in the RF and response properties of nociceptive neurons. In other animals pretreated with saline (0.3 microl) or MK-801 (3 microg/0.3 microl) microinjected into the Vo, mineral oil application to the pulp did not produce any significant changes in RF and response properties of nociceptive neurons. These findings indicate that the application of MO to the tooth pulp can induce significant neuroplastic changes in oralis nociceptive neurons and that central NMDA receptor mechanisms may be involved in these neuroplastic changes.