(-)-α-Bisabolol reduces orofacial nociceptive behavior in rodents.

The purposes of this study were to evaluate the anti-nociceptive effect of oral and topical administration of (-)-α-bisabolol (BISA) in rodent models of formalin- or cinnamaldehyde-induced orofacial pain and to explore the inhibitory mechanisms involved. Orofacial pain was induced by injecting 1.5% formalin into the upper lip of mice (20 µL) or into the temporomandibular joint (TMJ) of rats (50 µL). In another experiment, orofacial pain was induced with cinnamaldehyde (13.2 µg/lip). Nociceptive behavior was proxied by time (s) spent rubbing the injected area and by the incidence of head flinching. BISA (100, 200, or 400 mg/kg p.o. or 50, 100, or 200 mg/mL topical) or vehicle was administered 60 min before pain induction. The two formulations (lotion and syrup) were compared with regard to efficacy. The effect of BISA remained after incorporation into the formulations, and nociceptive behavior decreased significantly in all tests. The high binding affinity observed for BISA and TRPA1 in the molecular docking study was supported by in vivo experiments in which HC-030031 (a TRPA1 receptor antagonist) attenuated pain in a manner qualitatively and quantitatively similar to that of BISA. Blockers of opioid receptors, NO synthesis, and K+ ATP channels did not affect orofacial pain, nor inhibit the effect of BISA. In conclusion, BISA had a significant anti-nociceptive effect on orofacial pain. The effect may in part be due to TRPA1 antagonism. The fact that the effect of BISA remained after incorporation into oral and topical formulations suggests that the compound may be a useful adjuvant in the treatment of orofacial pain.

Evidence for the involvement of TNF-α and IL-1ß in the antinociceptive and anti-inflammatory activity of Stachys lavandulifolia Vahl. (Lamiaceae) essential oil and (-)-α-bisabolol, its main compound, in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Stachys lavandulifolia Vahl (Lamiaceae) is a medicinal plant widely used in Turkey and Iranian folk medicine due to its analgesic and anti-inflammatory properties, but little is known about its essential oil. AIM OF THIS STUDY: We studied the antinociceptive and anti-inflammatory effects of S. lavandulifolia essential oil (EOSl) and (-)-α-bisabolol (BIS), its main compound, in algogen-induced orofacial nociceptive behavior in mice, and assessed the possible involvement of pro-inflammatory cytokines in these profiles. MATERIALS AND METHODS: The GC-FID and GC-MS analysis of EOSl demonstrated the presence of (-)-α-bisabolol (56.4%), bicyclogermacrene (5.3%), δ-cadinene (4.2%) and spathulenol (2.9%) as the main compounds. Male Swiss mice were pretreated with EOSl (25 or 50mg/kg, p.o.), BIS (25 or 50mg/kg, p.o.), morphine (3mg/kg, i.p.) or vehicle (saline 0.9% with two drops of tween 80, 0.2%), before formalin- (20µl, 2%), capsaicin- (20µl, 2.5µg) or glutamate- (20µl, 25Mm) injection into the right upper lip (perinasal area) in mice. The anti-inflammatory profile of EOSl or BIS (50mg/kg) was assessed by the inflammatory response induced by carrageenan (2% in 0.2mL) in mice (pleurisy model). RESULTS: Our results showed that p.o. treatment with EOSl and BIS displayed significant inhibitory (p<0.05 or p<0.01 or p<0.001) effects in different orofacial pain tests on mice, but BIS proved to be more effective, significantly reducing nociceptive behavior in all tests including both phases of the formalin test. The analgesic effect is not related to any abnormality since EOSl- or BIS-treated mice exhibited no performance alteration in grip strength. Moreover, EOS1 and BIS exhibited a significant anti-inflammatory effect (p<0.001) in the pleurisy model of inflammation, which seems to be related to a significant reduction (p<0.05) of the pro-inflammatory cytokine TNF-α in BIS treatment, and of the pro-inflammatory cytokine IL-1ß (p<0.01) in EOS1 treatment. CONCLUSION: Our results corroborate the use of S. lavandulifolia in traditional medicine as an analgesic and anti-inflammatory, which seems to be related to (-)-α-Bisabolol, the main compound of EOSl.

Comfort evaluation of non occlusal intraoral appliance use during sleep in patients with muscular temporomandibular dysfunction / Evaluación del confort del uso durante el sueño de un aparato intraoral no oclusal en pacientes con disfunción temporomandibular muscular

The aim of this study was the evaluation of the discomfort level during the utilization of non oclusal intraoral appliance during sleep in patients with muscular temporomandibular dysfunction; time of acceptance; and the effectiveness of non oclusal intraoral appliance related to the relief of pain symptoms. We evaluated 30 patients from Orofacial Pain and Temporomandibular Dysfunction Clinic (UNIFESP/EPM/HSP) with muscular temporamandibular dysfunction, 25 females and 5 males, between 19 to 60 years. We used a non-oclusal intraoral appliance, based on the model developed by Minagi et al. (2001). Patients was conducted to use the appliance during all sleeping period e to persist in use, even when there was any kind of discomfort, which would be natural during the adaptation period, for 30 consecutive days. After this period, the researcher interviewed all patients, answering specific questions designed for this study. The mean time for adaptation was 4 days. Of all patients, 23.33 percent had no difficulty in adapting the appliance, with immediate acceptance. The gradual reduction in the intensity of myofascial pain and discomfort, as well as improving the quality of life in 78.3 percent of the sample confirmed the effectiveness of non-oclusal palatal intraoral appliance without occlusal contact in relieving the painful symptoms of muscular TMD.

El objetivo fue evaluar la respuesta al uso de un aparato intraoral no oclusal durante el sueño en pacientes con disfunción temporomandibular (DTM) muscular. Se evaluaron 30 pacientes de la Clínica de Dolor Orofacial y Disfunción Temporomandibular (UNIFESP/EPM/HSP) con diagnóstico de DTM muscular, 25 mujeres y 5 hombres, entre 19 y 60 años. Se utilizó un aparato intraoral no oclusal, basado en el modelo desarrollado por Minagi et al. (2001) y se evaluó el tiempo de adaptación al aparato y la eficacia en términos de reducción del dolor. Los pacientes utilizaron el aparato al acostarse y mientras dormían por 30 días contínuos. Después de este período, todos los pacientes fueron entrevistados. El tiempo medio para la adaptación fue de 4 días. De todos los pacientes, el 23,33 por ciento no tuvo ninguna dificultad de adaptación al aparato, con aceptación inmediata. La reducción gradual en la intensidad del dolor miofascial y el malestar, así como la mejora de la calidad de vida en el 78,3 por ciento de la muestra confirmó la eficacia del aparato intraoral para aliviar los síntomas dolorosos de DTM muscular.

Effect of low-level laser therapy on the post-surgical inflammatory process after third molar removal: study protocol for a double-blind randomized controlled trial.

BACKGROUND: Low-level laser therapy (LLLT) has been shown to modulate the inflammatory process without adverse effects , by reducing pain and swelling and promoting the repair of damaged tissues. Because pain, swelling and muscle spasm are complications found in virtually all patients following oral surgery for the removal of impacted teeth, this model has been widely used to evaluate the effects of LLLT on the inflammatory process involving bone and, connective tissue and the muscles involved in mastication. METHODS/DESIGN: After meeting the eligibility criteria, 60 patients treated at a Specialty Dental Center for the removal of impacted lower third molars will be randomly divided into five groups according to the type of laser therapy used at the end of surgery (intraoral irradiation with 660 nm laser; extraoral irradiation with 660 nm laser; intraoral irradiation with 808 nm laser; extraoral irradiation with 808 nm laser and no irradiation). To ensure that patients are blinded to the type of treatment they are receiving, the hand piece of the laser apparatus will be applied both intraorally and extraorally to all participants, but the device will be turned on only at the appropriate time, as determined by the randomization process. At 2 and 7 days after surgery, the patients will be evaluated by three blinded evaluators who will measure of swelling, mouth opening (muscle spasm evaluation) and pain (using two different pain scales). The 14-item Oral Health Impact Profile (OHIP-14) will be used to assess QOL. All data will be analyzed with respect to the normality of distribution using the Shapiro-Wilk test. Statistically significant differences between the experimental groups will be determined using analysis of variance, followed by a suitable post hoc test, when necessary. The significance level will be set at α = 0.05. DISCUSSION: The lack of standardization in studies with regard to the samples, methods and LLLT parameters complicates the determination of the actual effect of laser therapy on this model. The present study aims to provide a randomized, controlled, double-blind trial to compare four different LLLT parameters in relation to the outcomes of pain, swelling and muscle spasm following surgery for the extraction of impacted third molars and evaluate the effects os surgery on patients' quality os life (QOL). TRIAL REGISTRATION: Brazilian Registry of Clinical Trials - Rebec (RBR-6XSB5H).

Effect of different protocols for treating cavities in primary molars on the quality of life of children in Brazil--1 year follow-up.

The aim of this study was to test the hypothesis that the conventional restorative treatment (CRT) and the atraumatic restorative treatment (ART) protocols, in comparison with the ultra-conservative treatment (UCT) protocol, would increase the quality of life of children over a period of 1 year. Cavitated primary molars of 302 children 6-7 years of age were treated according to the CRT, ART and UCT protocols at the school compound. Children's parents completed the Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS) at baseline and one year later. Paired t-test, Chi-square test and ANOVA were applied in analysing the data. Questionnaires from 277 and 160 children were collected at baseline and after 1 year, respectively. A statistically significant difference in B-ECOHIS scores over the 1-year period was found for domains 'child symptoms' (P = 0.03) and 'child psychology' (P = 0.02). Treatment protocols did not statistically significantly influence the changes in B-ECOHIS scores over the 1-year period (P = 0.78). It can be concluded that the UCT protocol was as good as the two restorative protocols. All treatment protocols were effective in reducing children's experience of pain, their sleeping problems and their irritability and/or frustration levels over the 1-year period.

Effect of two routes of administration of dexamethasone on pain, edema, and trismus in impacted lower third molar surgery.

PURPOSE: The aim of the present study was to compare pain, edema, and trismus in the postoperative period following third molar surgery using 8 mg of dexamethasone administered either orally or through local injection. METHODS: A prospective, controlled, randomized trial was carried out involving 60 lower third molar surgeries in 67 patients between October 2008 and June 2009. The sample was randomly divided into three groups: group A (local injection), group B (tablets), and group C (control). In all cases, either ostectomy or crown sectioning was employed. On the second and seventh day following surgery, linear edema was determined using facial landmarks, and maximal mouth opening measurements were performed. Postoperative pain was recorded using a visual analog scale. RESULTS: Patient age ranged from 14 to 37 years (mean, 21.0 years). With regard to pain, edema, and trismus, the two administration routes tested (local injection and tablets) demonstrated similar efficacy, and both methods achieved better results in comparison to the control group. CONCLUSION: Both the oral administration and local injection of dexamethasone proved effective in reducing pain, edema, and trismus compared to control group following lower third molar surgeries, achieving similar results.

A double-blind, randomized clinical trial assessing the effects of a single dose of preemptive anti-inflammatory treatment in orthodontic pain.

OBJECTIVE: Strategies about how to mitigate or prevent the appearance of pain associated with orthodontic treatment are poorly defined. Herein we conduct a prospective, double-blind, randomized controlled clinical trial assessing the effects of a single dose of anti-inflammatory medication to preemptively treat pain following the placement of orthodontic separating elastics. MATERIALS AND METHODS: Fifty one participants were randomly selected and divided into three groups: (a) 17 patients took placebo one hour prior to the elastic separator placement; (b) 17 patients took 400 mg lumiracoxib one hour prior to the elastic separator placement; and (c) 17 patients didn't take anything prior to the procedure. Discomfort and pain intensity levels were measured by an analog 10-points visual scale at 2 hours, 6 hours, 24 hours, 2 days and 4 days after the procedure. RESULTS: When comparing the three groups (no treatment, placebo and active) no significant differences were found. Nonetheless, pain severity was always lower in individuals receiving the drug. Similar pattern was seen for the other time points. CONCLUSIONS: Our study does not support the use of a single dose of medication with anti-inflammatory properties in the preemptive treatment of pain following an orthodontic procedure. Further investigation is required in order to ascertain whether recurrent doses (vs a single dose) can impact outcomes.

Botulinum toxin type-A effect as a preemptive treatment in a model of acute trigeminal pain: a pre-clinical double-blind and placebo-controlled study.

The purpose of this study was to investigate if botulinum neurotoxin type-A (BoNT/A) had a preemptive antinociceptive effect in a formalin-induced orofacial pain model (FT). To test this hypothesis, male Rattus norvegicus were injected with isotonic saline solution 0.9% or BoNT/A administered as a 40 µl bolus, lateral to their nose, at 24 hours, 8, 15, 22, 29 or 36 days pre-FT. The procedures were repeated 42 days later. Influence on motor activity was assessed through the open-field test. Pain scores corresponded to the time spent rubbing and flicking the injected area. Animals pre-treated with BoNT/A at the first protocol (8 days subgroup) showed reduced inflammatory scores (p=0.011). For the other groups no significant results were observed at any phase. Motor activity was similar in both groups. BoNT/A showed to be effective preventing inflammatory pain up to eight days after the first treatment, an effect not reproduced on the second dose administration.

Botulinum toxin type-A effect as a preemptive treatment in a model of acute trigeminal pain: a pre-clinical double-blind and placebo-controlled study / Toxina botulínica do tipo-A no tratamento preemptivo da dor trigeminal aguda: estudo pré-clínico duplo cego placebo controlado

The purpose of this study was to investigate if botulinum neurotoxin type-A (BoNT/A) had a preemptive antinociceptive effect in a formalin-induced orofacial pain model (FT). To test this hypothesis, male Rattus norvegicus were injected with isotonic saline solution 0.9 percent or BoNT/A administered as a 40 μl bolus, lateral to their nose, at 24 hours, 8, 15, 22, 29 or 36 days pre-FT. The procedures were repeated 42 days later. Influence on motor activity was assessed through the open-field test. Pain scores corresponded to the time spent rubbing and flicking the injected area. Animals pre-treated with BoNT/A at the first protocol (8 days subgroup) showed reduced inflammatory scores (p=0.011). For the other groups no significant results were observed at any phase. Motor activity was similar in both groups. BoNT/A showed to be effective preventing inflammatory pain up to eight days after the first treatment, an effect not reproduced on the second dose administration.

O objetivo deste estudo foi investigar o efeito preemptivo da neurotoxina botulínica do tipo/A (NTBo/A) através de um modelo de dor orofacial induzida pelo teste da formalina (TF). Rattus norvegicus machos foram injetados no lábio superior com solução salina isotônica 0,9 por cento (SSI) ou NTBo/A (subgrupos 24 horas, 8, 15, 22, 29 ou 36 dias) antes do TF, em dois tratamentos farmacológicos e respectivas avaliações intercalados por 42 dias. Os escores da dor corresponderam ao tempo de fricção da região injetada. Após o primeiro pré-tratamento com NTBo/A no subgrupo 8 dias os escores da fase inflamatória foram menores do que no grupo SSI (p=0,011). Todas as outras comparações não foram significativas. Nos testes de atividade motora não ocorreram diferenças entre SSI e NTBo/A. A NTBo/A pode ser considerada como tratamento preemptivo das dores orofaciais quando utilizada até oito dias antes do estímulo álgico, não havendo consistência terapêutica após um segundo tratamento.

Tenoxicam controls pain without altering orthodontic movement of maxillary canines.

OBJECTIVES: To study the efficacy of tenoxicam for pain control, its potential for preemptive analgesia, and its influence on the orthodontic movement of upper canine teeth. DESIGN: This was a randomized controlled double-blind cross-over study. The patients were divided into three groups. Two groups received tenoxicam in daily doses of 20 mg orally for 3 days. Group A received the first dose of the drug before orthodontic activation and group B, just afterwards. Group C (control) received a placebo for 3 days. All groups had access to 750 mg of paracetamol up to four times a day. Three orthodontic activations were performed at 30-day intervals. Each patient belonged to two different groups. Pain intensity was assessed using a descriptive Pain Scale and a Visual Analog Scale. SETTING AND SAMPLE POPULATION: Private clinic; 36 patients undergoing bilateral canine tooth retraction. RESULTS: The statistical analysis did not show any difference in movement between the active groups and the control at any time. There was no statistical difference between the groups that received tenoxicam. Pain intensity in these groups was lower than in the placebo group. The difference in pain intensity between the active groups and the control was greatest at the assessment made 12 h after activation and it tended to zero, 72 h after activation. CONCLUSIONS: Tenoxicam did not influence orthodontic movement of the upper canines. It was effective for pain control and did not present any preemptive analgesic effect.

Evaluation of different occlusal splints and counselling in the management of myofascial pain dysfunction.

The aim of this study was to compare the effectiveness of different occlusal splints associated with counselling and self-care in the management of signs and symptoms of myofascial pain. In a double-blind controlled clinical trial, 42 myofascial pain patients with chief complaint of pain in the masseter muscle area were randomly assigned to 1 of the 3 experimental groups: hard (HS), soft (SS) or non-occluding (NS) occlusal splints. The Modified Symptom Severity Index (Mod-SSI) and tenderness to palpation were used as outcome measures during a 90-day follow-up. All patients improved over time and all splints offered the benefit. The results showed that all the three different appliances (HS, SS, and NS) associated with counselling were able to equally reduce the Mod-SSI (symptoms-Tukey test) and digital palpation (signed Kruskal-Wallis) test between baseline and 90 days.

Antinoceptive effect of triterpenoid alpha,beta-amyrin in rats on orofacial pain induced by formalin and capsaicin.

The effects of alpha,beta-amyrin, a pentacyclic triterpene isolated from Protium heptaphylum was investigated on rat model of orofacial pain induced by formalin or capsaicin. Rats were pretreated with alpha,beta-amyrin (10, 30, and 100mg/kg, i.p.), morphine (5mg/kg, s.c.) or vehicle (3% Tween 80), before formalin (20 microl, 1.5%) or capsaicin (20 microl, 1.5 microg) injection into the right vibrissa. In vehicle-treated controls, formalin induced a biphasic nociceptive face-rubbing behavioral response with an early first phase (0-5 min) and a late second phase (10-20 min) appearance, whereas capsaicin produced an immediate face-rubbing (grooming) behavior that was maximal at 10-20 min. Treatment with alpha,beta-amyrin or morphine significantly inhibited the face-rubbing response in both test models. While morphine produced significant antinociception in both phases of formalin test, alpha,beta-amyrin inhibited only the second phase response, more prominently at 30 mg/kg, in a naloxone-sensitive manner. In contrast, alpha,beta-amyrin produced much greater antinociceptive effect at 100mg/kg in the capsaicin test, which was also naloxone-sensitive. These results provide first time evidence to show that alpha,beta-amyrin attenuates orofacial pain at least, in part, through a peripheral opioid mechanism but warrants further detailed study for its utility in painful orofacial pathologies.

Efficacy of 1% ropivacaine gel for topical anesthesia of human oral mucosa.

OBJECTIVE: To evaluate the efficacy of 1% ropivacaine for topical anesthesia in dentistry. METHOD AND MATERIALS: Thirty healthy volunteers randomly (blind crossover) received the following treatments: 20 mg of 1% ropivacaine gel (ropivacaine-20), 60 mg of 1% ropivacaine gel (ropivacaine-60), 20 mg of the eutectic mixture of local anesthetics 2.5% lidocaine and 2.5% prilocaine (EMLA cream, AstraZeneca; EMLA-20), 60 mg of EMLA (EMLA-60), 20 mg of 20% benzocaine gel (Benzotop, DFL; benzocaine-20), and 60 mg of 20% benzocaine gel (benzocaine-60), applied on the maxillary buccal fold of the right canine at different sessions. Pain was assessed by visual analog scale (VAS) and 11-point box scale (BS-11) after the insertion of 30-gauge needles. Soft tissue anesthesia was measured by pinprick test. Data were analyzed by Friedman and Pearson correlation tests. RESULTS: All the topical anesthetics evaluated showed similar performance in relation to the pain perceived after needle insertion (P >.05), and there were no significant differences among groups considering VAS or BS-11 (P = .177 and P = .179, respectively). The duration of soft tissue anesthesia was not statistically significantly different for ropivacaine-20, EMLA-20, benzocaine-20, ropivacaine-60, EMLA-60, and benzocaine-60, but EMLA-60 showed significantly longer duration than the other agents (P <.05). CONCLUSION: All topical anesthetics were similar in reducing pain to needle insertion. EMLA-60 promoted longer duration of soft tissue anesthesia.

Anesthetic efficacy and pain induced by dental anesthesia: the influence of gender and menstrual cycle.

OBJECTIVE: To assess the influence of the menstrual cycle and oral contraceptives on pain sensitivity and local anesthetic effectiveness. STUDY DESIGN: Thirty volunteers were designated into 3 groups (n = 10): group 1, women using contraceptives; group 2, women not using contraceptives; and group 3, men. Groups 1 and 2 had a buccal infiltration of 2% lidocaine with 1:100,000 epinephrine at the upper-right canine during each one of the 5 phases of the menstrual cycle and group 3 at a randomly selected day. Pain threshold, latency period, and pulpal anesthesia were measured with an electrical pulp tester. Injection discomfort was recorded. Data were analyzed with Friedman and Kruskal-Wallis tests. RESULTS: Pain threshold was higher in men; however, there were no significant differences (P > .05) in anesthetic duration and injection discomfort. CONCLUSION: Injection discomfort and clinical effectiveness of local anesthetics are not related to sex, phases of the menstrual cycle, or use of oral contraceptives.

Pulp-dentine complex changes and root resorption during intrusive orthodontic tooth movement in patients prescribed nabumetone.

Pulpitis, external root resorption, and pain may be experienced during orthodontic movement. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested to control these changes. The purpose of this study was to observe pulp-dentinal reactions, root resorption, tooth pain, and tooth movement after the application of a 4-ounce intrusive orthodontic force to human maxillary first premolars in patients given the NSAID nabumetone. Thirty-four maxillary first premolars were evaluated. A placebo was prescribed to 17 patients after an intrusive force was activated and reactivated for an 8-week period on the right side. The same procedure was repeated on the left side after patients were given nabumetone. Pulp-dentinal reactions and external root resorption were evaluated by histology. Pain and movement were also evaluated. Nabumetone was found to be useful in reducing pulpitis, external root resorption, and pain caused by intrusive orthodontic movement, without altering tooth movement in response to the application of orthodontic force.

Articaine and lignocaine efficiency in infiltration anaesthesia: a pilot study.

AIM: The purpose of this study was to evaluate the onset of action of pulpal and soft tissue anaesthesia, and pain experience after buccal and palatal infiltrative injections with 4% articaine with 1:100,000 adrenaline, and 2% lignocaine with 1:100,000 adrenaline. METHOD: A double blind cross-over study was conducted with 20 healthy adult subjects who, in two appointments at least two weeks apart, randomly received an infiltration anaesthesia with the solutions in the buccal and palatal regions of the upper right canine. The tooth was tested with a pulp tester before (to establish its baseline response), and after the injection, until return to the base threshold level. The pain experience caused by palatal injection was verified by the visual analogue scale (VAS). Data were analysed using Wilcoxons test (alpha = 0.05). RESULTS: There were no significant statistical differences between the solutions with respect to VAS (p = 0.45), onset of action (p = 0.80) and pulpal (p = 0.08) and soft tissue (p = 0.18) anaesthesia duration, although pulpal anaesthesia may have reached statistical significance if a higher number of volunteers had been used. CONCLUSION: Under the conditions of this study it can be concluded that both anaesthetic solutions showed similar pain experience.