Systemic Chronic Treatment with Cannabidiol in Carioca High- and Low-Conditioned Freezing Rats in the Neuropathic Pain Model: Evaluation of Pain Sensitivity.

Studies have shown high comorbidity of anxiety disorder and chronic pain; generalized anxiety disorder (GAD) and neuropathic pain are among these pathologies. Cannabidiol (CBD) has been considered a promising treatment for these conditions. This study investigated whether chronic systemic treatment with CBD alters pain in high- (CHF) and low-freezing (CLF) Carioca rats (GAD model) and control rats (CTL) submitted to chronic neuropathic pain. The rats were evaluated in the sensory aspects (von Frey, acetone, and hot plate tests) before the chronic constriction injury of the ischiatic nerve (CCI) or not (SHAM) and on days 13 and 23 after surgery. Chronic treatment with CBD (5 mg/kg daily) was used for ten days, starting the 14th day after surgery. The open field test on the 22nd also evaluated locomotion and anxiety-like behavior. CBD treatment had an anti-allodynic effect on the mechanical and thermal threshold in all lineages; however, these effects were lower in the CHF and CLF lineages. Considering emotional evaluation, we observed an anxiolytic effect in CTL+CCI and CHF+CCI after CBD treatment and increased mobility in CLF+SHAM rats. These results suggest that the CBD mechanical anti-allodynic and emotional effects can depend on anxiety level.

Application of photobiomodulation for chronic pain-related TMD on pain points versus pre-established points: Randomized clinical trial.

Photobiomodulation therapy (PTB) is a therapeutic possibility for temporomandibular disorders (TMD), but its effectiveness and protocols for use remain controversial. This study is a RCT that compared the effectiveness of PTB on pain points of the masticatory muscles and TMJs, located through palpation versus application of pre-established points in women with painful TMD, diagnosis by DC/TMD (Diagnostic Criteria for Temporomandibular Disorders - Brazilian Portuguese version). Therefore, a total sample of 54 women, aged between 18 and 60 years, was investigated. Volunteers were randomly randomized and PTB was applied in four different groups with a dose of 4 J and 6 J divided into pre-established application points (PE - G1) and pain points (PD - G2) - Groups 4PE, 4PD, 6PE and 6PD. Four laser applications were performed with a wavelength of 780 nm, one session per week, totaling one month of therapy. The following assessments were performed: DC/TMD, Brief Pain Inventory (BPI), McGill Questionnaire - Short Version (SF-MPQ) and Pain Intensity, Visual Analogue Scale (VAS). Friedman's test was used for within-group comparisons, while the Mann-Whitney test was used for between-group comparisons (p < 0.05). According to the results, laser application on pain points (G2) was more effective. McGill's results showed that regardless of dose, the pain point application group had better outcomes (p = 0.004). Pain intensity evaluation (last days) also showed that application at the pain points was more effective regardless of dose (p = 0.0002). Medians and interquartile deviations showed overall that PTB was more effective at pain points, with a trend towards better outcomes at the 6 J dose. Therefore, it can be concluded that in women with chronic painful TMD, the application of PTB at pain points is more effective than the application at pre-established points. Therefore, individualized PTB protocols are proposed, based on examination palpation of the masticatory structures.

Phenotypic analysis of discordant monozygotic twins for pain-related temporomandibular joint disorder. Case report / Análise fenotípica de gêmeas monozigóticas discordantes para disfunção temporomandibular dolorosa. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: The design of research with monozygotic twins discordant for the disease has emerged as a powerful tool for the detection of phenotypic risk factors. The aim of this study is to report a clinical case of monozygotic twins discordant for pain-related temporomandibular joint disorder (TMD) from a cognitive-behavioral-emotional phenotypic analysis, from the comparison of clinical variables of pain, history of exposure to painful procedures in early childhood, and coping with pain. CASE REPORT: TMD-Twin presented a diagnosis of painful (myofascial pain with referral) and joint (disk displacement with reduction) TMD according to the criteria of the DC/TMD. Control-Twin did not show TMD, however she presented other chronic pains. TMD-Twin showed reduced pressure pain threshold, hyperalgesia in trigeminal and extra-trigeminal regions compared to the Control-Twin. TMD-Twin was more exposed to painful procedures and emotional events due to congenital heart problems. Both had central sensitization based on the Central Sensitization Inventory, although TMD-Twin had more catastrophic thoughts about pain. TMD-Twin presented an internal locus of control. CONCLUSION: Both monozygotic twins presented a chronic pain phenotype, although they were discordant with the TMD-related pain. The main differences were the lower pressure pain threshold and higher hyperalgesia locally presented by TMD-Twin. The internal locus of control indicates greater pain sensitivity, with better coping of the painful experience for the TMD-Twin. One possible explanation for this clinical condition can be that painful experiences in early childhood have shaped a phenotype of greater sensitivity with better coping and resilience to the painful condition.

RESUMO JUSTIFICATIVA E OBJETIVOS: O desenho da pesquisa com gêmeos monozigóticos discordantes para a doença surgiu como uma ferramenta poderosa para a detecção de fatores de risco fenotípicos. O objetivo deste estudo foi relatar um caso clínico de gêmeas monozigóticas discordantes para disfunção temporomandibular (DTM) dolorosa a partir de análise fenotípica cognitivo-comportamental-emocional entre elas, por meio de comparação de variáveis clínicas de dor, histórico de exposição a procedimentos dolorosos na primeira infância e enfrentamento de dor (autoeficácia e lócus de controle). RELATO DO CASO: A gêmea-DTM apresentou diagnóstico de DTM dolorosa (dor miofascial com referência) e articular (deslocamento do disco com redução) segundo os critérios do Critérios de Diagnóstico para Distúrbios Temporomandibulares. A gêmea--controle não apresentou DTM, contudo apresentou manifestação clínica de outras dores crônicas. A gêmea-DTM apresentou limiar de dor à pressão reduzido, hiperalgesia em regiões trigeminais/extra-trigeminais quando comparados à gêmea-controle, que na primeira infância foi mais exposta a procedimentos dolorosos devido a problemas cardíacos congênitos. Ambas apresentaram sensibilização central de acordo com o Inventário de Sensibilização Central, embora a gêmea-DTM apresentou mais pensamentos catastróficos sobre a dor. A gêmea-DTM apresentou lócus de controle interno. CONCLUSÃO: Ambas as gêmeas apresentaram fenótipo de dor crônica, apesar do fato de serem discordantes para a DTM. Dentre as avaliações, as que mais diferiram entre o par foram o baixo limiar de dor à pressão e hiperalgesia local presentes na gêmea com DTM. O lócus de controle interno associado à maior sensibilidade indicou melhor enfrentamento da experiência dolorosa para a gêmea-DTM. Uma possível explicação para esta manifestação clínica está pautada na hipótese de que experiências dolorosas na primeira infância vivenciadas por ela tenham moldado um fenótipo de maior sensibilidade com melhor enfrentamento e resiliência frente à condição dolorosa.

Follow-up results of a randomized clinical trial for low-level laser therapy in painful TMD of muscular origins.

Objective: To characterize short- and long-term assessment of the low-intensity laser therapy (LLLT) effectiveness in women with TMD of muscular origins and to evaluate whether the information about the treatment received (active or placebo) modifies the pain intensity.Methods: Forty-one women with painful TMD (31.7 ± 5.2 years) were divided into laser (n = 20) and placebo (n = 21) groups. The pain intensity was measured at the baseline, after the LLLT (T8), 6 and 12 months. At the 6-month follow-up, the groups received information about the active or placebo treatment.Results: At T8 and 6-month, both active and placebo LLLT were effective in reducing pain (p < .05). After one year, the groups showed similar pain. Active LLLT was more effective in reducing pain palpation (p = .001) and referred pain (p = .04) in the region of the TMJs. The information about the treatment modified the perceived pain intensity.Conclusion: Active and placebo LLLT are effective for painful TMD of muscular origins in the short-term. Information about the treatment impairs the subjective perception of pain.

Intervenção baseada em mindfulness reduz parâmetros de sensibilidade em mulheres com DTM dolorosa crônica / Mindfulness-based intervention reduces sensitivity parameters in women with chronic painful TMD / La intervención basada en la atención plena reduce los parámetros de sensibilidad en mujeres con TMD dolorosa crónica

OBJETIVO: analisar parâmetros clínicos sugestivos de sensibilização central em mulheres com disfunção temporomandibular dolorosa crônica antes e após uma intervenção baseada em mindfulness. MÉTODO: onze mulheres com idade entre 27 e 44 anos (36,36 ± 5,61), com diagnóstico de disfunções temporomandibulares dolorosa crônica (Diagnostic Criteria for Temporomandibular Disorders), participaram do estudo. A hiperalgesia, a alodinia e o limiar de dor à pressão foram avaliados em pontos trigeminais e extra-trigeminais antes e após a intervenção baseada em mindfulness, bem como a aplicação do questionário Mindful Attention Awareness Scale. O programa de mindfulness de 8 semanas foi oferecido às participantes do estudo, com base no protocolo Mindfulness Trainings International, em sessões semanais de 2 horas e uma sessão de 4 horas. RESULTADOS: houve redução significativa da alodinia, da hiperalgesia e aumento do limiar de dor à pressão, além de aumento significativo do nível de atenção plena (p < 0,05) enquanto marcador de efetividade da intervenção baseada em mindfulness oferecida. CONCLUSÃO: índices mais saudáveis nos parâmetros clínicos sugestivos de sensibilização central investigados após a intervenção, representam melhora significativa na relação da pessoa com quadro de enfermidade crônica geradora de experiências desagradáveis contínuas como a disfunções temporomandibulares.

OBJECTIVE: manifestations of allodynia and hyperalgesia are commonly present in chronic painful temporomandibular disorder. Studies point to the benefits of people with chronic pain undergoing mindfulness-based interventions, by demonstrating brain, hormonal, and clinical changes. This study aimed to analyze clinical parameters suggestive of central sensitization (pressure pain threshold, allodynia, and hyperalgesia) in women with chronic painful temporomandibular disorder before and after a mindfulness-based intervention, through a before-and-after intervention study, longitudinal, uncontrolled. METHOD: the analysis included 11 women chosen at random from a total of 20, aged between 27 and 44 years (36.36 ± 5.61), diagnosed with chronic painful temporomandibular disorder according to the Diagnostic Criteria for Temporomandibular Disorders protocol and who completed the 8-week mindfulness-based intervention program. Hyperalgesia, allodynia, and pressure pain threshold were tested at trigeminal and extra-trigeminal points before and after the intervention as well as the application of the questionnaire to measure the level of mindfulness (Mindful Attention Awareness Scale). The 8-week mindfulness program was offered to the study participants, based on the Mindfulness Trainings International - protocol, in weekly 2-hour sessions and a 4-hour session (immersion). RESULTS: the results pointed to a reduction in allodynia, hyperalgesia and an increase in pressure pain threshold, with significant differences in several tested points (p <0.05). The changes identified were accompanied by a significant increase in the level of mindfulness (p < 0.05). CONCLUSION: healthier indexes in clinical parameters suggestive of central sensitization investigated after the intervention represent a significant improvement in the person's relationship with a chronic illness that generates continuous unpleasant experiences such as temporomandibular disorder. Thus, the practice of mindfulness represents an appropriate and particularly interesting care because it is a low-cost, non-invasive intervention with low evidence of adverse effects.

OBJETIVO: las manifestaciones de alodinia y hiperalgesia y están comúnmente presentes en lo trastorno temporomandibular doloroso crónico. Los estudios señalan los beneficios de las personas con dolor crónico que se someten a intervenciones basadas en la atención plena, al demostrar cambios cerebrales, hormonales y clínicos. El objetivo de este estudio fue analizar parámetros clínicos sugestivos de sensibilización central (umbral de dolor por presión, alodinia e hiperalgesia) en mujeres con trastorno temporomandibular doloroso crónico antes y después de una intervención basada en la atención plena, a través de un estudio de intervención antes y después, longitudinal, sin control. MÉTODO: el análisis incluyó a 11 mujeres elegidas al azar de un total de 20, con edades entre 27 y 44 años (36.36 ± 5.61), diagnosticadas con trastorno temporomandibular doloroso crónico de acuerdo con protocolo Criterios de diagnóstico para trastornos temporomandibulares y que completaron el 8- programa de intervención basado en mindfulness de una semana. La hiperalgesia, la alodinia y el umbral de dolor por presión se probaron en los puntos trigémino y extra-trigémino antes y después de la intervención, así como también en la aplicación del cuestionario para medir el nivel de atención plena (Escala de conciencia de atención plena). El programa de atención plena de 8 semanas se ofreció a los participantes del estudio, basado en el protocolo Mindfulness Trainings International, en sesiones semanales de 2 horas y una sesión de 4 horas (inmersión). RESULTADOS: los resultados apuntaron a una reducción en la alodinia, hiperalgesia y un aumento en la umbral de dolor por presión, con diferencias significativas en varios puntos probados (p <0.05). Los cambios identificados fueron acompañados por un aumento significativo en el nivel de atención plena (p <0.05), como un marcador de la efectividad de la capacitación ofrecida para la práctica de la atención plena. CONCLUSIÓN: los índices más saludables en los parámetros clínicos sugestivos de sensibilización central investigados después de la intervención, representan una mejora significativa en la relación de la persona con una enfermedad crónica que genera experiencias continuas desagradables como trastorno temporomandibular doloroso crónico. Por lo tanto, la práctica de la atención plena representa una atención aplicable y particularmente interesante porque es una intervención no invasiva de bajo costo con poca evidencia de efectos adversos.

Non-specific effects and clusters of women with painful TMD responders and non-responders to LLLT: double-blind randomized clinical trial.

The aim was to analyze the non-specific effects (placebo, spontaneous remission, and regression to the mean) of the low-level laser therapy (LLLT) in women with myofascial pain (painful temporomandibular disorder (TMD)), as well as to differentiate between responders and non-responder clusters to active and placebo LLLT according to the anxiety levels, salivary cortisol, use of oral contraceptives, and premenstrual period. Sixty-four women diagnosed with myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD)) were included, divided into laser (n = 20), placebo group (n = 21), and 23 controls (without treatment (WT)). The LLLT applied was 780 nm, masseter and temporal = 5 J/cm2 (20 mW-0.5 W/cm2), and TMJ area = 7.5 J/cm2 (30 mW-0.8 W/cm2), eight sessions, twice a week. The pain intensity (visual analogue scale (VAS)), anxiety (Beck Anxiety Inventory), salivary cortisol, and menstrual cycle's data at the baseline, T1-T8, and 30 days after LLLT (follow-up) were evaluated. The laser group showed 80% of pain reduction, placebo 85%, and WT 43% in T8. Women with severe anxiety and at the premenstrual period did not reduce pain with any LLLT. Active and placebo LLLT had similar effectiveness during the treatment period; however, women with moderate anxiety, cortisol levels above 10 ng/ml, and without contraceptive use maintain analgesia longer with active LLLT than placebo (follow-up 30 days). Women with low levels of anxiety, salivary cortisol below 10 ng/ml, and with contraceptive use showed the higher pain reduction. The analgesia promoted by LLLT in women with myofascial pain is a result of non-specific effects during the treatment period, although active LLLT is more effective in maintaining the analgesia after treatment (30 days) for the cluster of women with moderate anxiety, salivary cortisol above 10 ng/ml, and without contraceptive use.

Effectiveness of low-level laser therapy on pain intensity, pressure pain threshold, and SF-MPQ indexes of women with myofascial pain.

Women with temporomandibular disorders (TMD) frequently report pain areas in body regions. This process is associated with central sensitization phenomena, present in chronic pain. The low-level laser therapy (LLLT) has been reported as a therapeutic option for the painful TMD treatment. The aim of this study was to analyze the effect of LLLT on pain intensity (visual analogue scale, VAS), pain sensitivity in orofacial and corporal points (pressure pain threshold, PPT), and on Short Form-McGill Pain Questionnaire (SF-MPQ) indexes of women with myofascial pain (subtype of muscle TMD). Ninety-one women (18-60 years) were included in the study, among which 61 were diagnosed with myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorder-Ia and Ib) and were divided into laser (n = 31) and placebo group (n = 30), and 30 were controls. The LLLT was applied at pre-established points, twice a week, eight sessions (780 nm; masseter and anterior temporal = 5 J/cm2, 20 mW, 10 s; TMJ area = 7.5 J/cm2, 30 mW, 10 s). Pain intensity, pain sensitivity, and the SF-MPQ indexes were measured at the baseline, during laser sessions, and 30 days after treatment. For intra-group comparisons, the Friedman test was performed, and for inter-group, the Mann-Whitney test. Increased pain sensitivity was found in women with myofascial pain when compared to controls (p < 0.05). There was a reduction in pain intensity for both groups after LLLT. The LLLT did not change the PPT for any group (p > 0.05). Active laser and placebo reduced the indexes of sensory, total pain, and VAS, maintaining the results after 30 days; there was a reduction in the affective pain rating index for both groups, with no maintenance after 30 days for placebo, and the present pain intensity decreased in the laser group and did not change in the placebo after LLLT. In conclusion, the LLLT active or placebo are effective in reducing the overall subjective perception of myofascial pain (VAS and SF-MPQ indexes); however, they have no effectiveness in reducing the pain sensitivity in orofacial and corporal points (PPT increase).

Experimental tooth movement and photobiomodulation on bone remodeling in rats.

Photobiomodulation (PBM) is a therapy induced by a specific type of laser that affects biologic systems through non-thermal ways. The study of its basic mechanism has gained interest since little is known about the causes of the different effects of this treatment. In the present study, we investigated the action of the PBM application rate changes in the peri-implant tissues in rats subjected to tooth movement in different periods. Wistar rats (±250 g) received an apparatus in the region of the central incisors superiors tightly (70 g) or not, and they were also subjected to one or three PBM sessions. After 7 or 14 days, the rats were subjected to euthanasia and the jaws were dissected and processed for histology. For analysis, serial sections were made that were stained by Picrosirius Red for analysis of collagen fibers, Masson's trichrome for newly formed bone scan, and Hematoxylin-Eosin for quantification of osteoblasts. PBM applied in one or three sessions increased the population of osteoblasts. Still, the application of three sessions of PBM increased the density of collagen fibers and new bone formation compared to the controls. An increase was observed in the interincisal distance in irradiated groups with three PBM sessions and the application of force for both 7 or 14 days. These findings suggest that PBM can contribute positively to the orthodontic movement. So the laser therapy can be used as an adjunct procedure to be performed concurrently for orthodontic treatment in the dental clinic.

Functional mapping of the periaqueductal gray matter involved in organizing tonic immobility behavior in guinea pigs.

Tonic immobility behavior (TI) is an innate response characterized by profound motor inhibition that is exhibited by prey when physical contact with a predator is prolonged and the situation inescapable. The periaqueductal gray matter (PAG) is intimately associated with the somatic and autonomic components of defensive reactions. This study investigated whether the TI response was able to recruit specific functional columns of the PAG by examining c-fos immunolocalization in guinea pigs. In the TI group, the innate response was invoked in animals through inversion and physical contention for at least 15 min. In the control group, the animals were physically manipulated only. Our results demonstrate that the defensive behavior of TI is capable of promoting the expression of Fos protein in different areas of the PAG, with higher levels of staining in the ventrolateral (vl) and lateral (l) columns. In addition, our results demonstrate increased Fos immunoreactivity (FOS-IR) in the dorsal raphe nucleus, the Edinger-Westphal nucleus, the cuneiform nucleus and the superior colliculus. In contrast, there were no significant alterations in the number of FOS-IR cells in the inferior colliculus or the oculomotor nucleus. Analysis of the results suggests that neuronal activation after the TI response differs by functional column of the PAG.

Tooth movement activates the central amygdala and the lateral hypothalamus by the magnitude of the force applied.

OBJECTIVE: To determine if the magnitude of the force used to induce incisor tooth movement promotes distinct activation in cells in the central amygdala (CEA) and lateral hypothalamus (LH) of rats. Also, the effect of morphine on Fos immunoreactivity (Fos-IR) was investigated in these nuclei. MATERIALS AND METHODS: Adult male rats were anesthetized and divided into six groups: only anesthetized (control), without orthodontic appliance (OA), OA but without force, OA activated with 30g or 70g, OA with 70g in animals pretreated with morphine (2 mg/kg, intraperitoneal). Three hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing CEA and LH were processed for Fos protein immunohistochemistry. RESULTS: The results show that in the control group, the intramuscular injection of a ketamine/ xylazine mixture did not induce Fos-IR cells in the CEA or in the LH. Again, the without force group showed a little Fos-IR. However, in the 70g group the Fos-IR was the biggest observed (P < .05, Tukey) in the CEA and LH compared with the other groups. In the 30g group, the Fos-IR did not differ from the control group, the without OA group, and the without force group. Furthermore, pretreatment with morphine in the 70g group reduced Fos-IR in these regions. CONCLUSIONS: Tooth movement promotes Fos-IR in the CEA and LH according to the magnitude of the force applied.

Estresse como possível fator de risco para a doença periodontal: revisão da literatura / Stress as possible risk factor for periodontal disease: literature review

Ao longo dos anos os estudos epidemiológicos têm demonstrado que a doença periodontal não afeta os pacientes de uma forma padrão. Isso fez com que os pesquisadores propusessem classificações para as diferentes formas da doença. Além disso, fatores de risco como diabetes mellitus, tabagismo, dentre outros, vêm sendo identificados como possíveis razões para as diferentes formas de progressão da doença. A relação entre estresse e doença periodontal é estudada desde a metade do século passado, sendo, a maioria dos casos, associados a formas necrosantes da doença. Nos últimos anos, estudos observacionais têm encontrado uma relação positiva entre o estresse e formas mais frequentes da doença, como a periodontite crônica. Esses estudos apontam o estresse como um possível fator de risco para a doença periodontal uma vez que, frequentemente, os fatores já conhecidos não são suficientes para explicar o início e progressão da doença. Assim, o objetivo desta revisão foi avaliar o estado atual de entendimento do estresse como um fator de predisposição ao desenvolvimento da doença periodontal.

A long of the years epidemiological studies have been demonstrated that periodontal disease do not affect patients in the same pattern way. Because of this fact, classifications have been proposed for researchers for different kinds of the disease. Beyond that, risk factors have been identified such as, diabetes mellitus, smoking, and others, have been identified as possible reasons for different ways of the disease progression. The relation between stress and periodontal disease has been studied since the middle of last century. Most of the times, it is related with necrotizing forms of the disease. In the last years, observational studies have found a positive relation between stress and more common forms of the disease, such as chronic periodontites. Those studies indicated the stress asa possible risk factor for periodontal disease, once, in many cases, the risk factors already known are not enough to explain the beginning and progression of the periodontal disease. Thus, the aim of this study was to evaluate the actual status about stress as a factor of predisposition to the development of periodontal disease