Antinociceptive effect of ultra-low dose naltrexone in a pre-clinical model of postoperative orofacial pain.

Painmanagement after oral surgeries is essential to enhance recovery, reduce negative outcomes and improve the experience of the patient. Naltrexone (NTX) is a non-selective opioid receptor antagonist that has been shown to modulate neuro-inflammation when employed in low to ultra-low doses. In addition, ultra-low dose naltrexone (ULDN) has been shown to potentiate opioids' analgesia and to have opioid-sparing effects. Herein it was investigated the effect of ULDN in a model of postoperative orofacial pain in rats, and it was tested the hypothesis that blockade of TLR4-signalling pathway contributes to its antinociceptive effect. Systemic NTX reduced heat hyperalgesia in female rats and heat and mechanical hyperalgesia in male rats after incision surgery. Combined treatment with NTX and morphine, both at ineffective doses, resulted in a significant reduction of heat hyperalgesia in male rats. NTX injection at the incision site failed to change heat hyperalgesia, but injection at the trigeminal ganglion (TG) or subnucleus caudalis (Sp5C) caused a significant reduction in heat hyperalgesia. At these sites, blockade of TLR4 impeded NTX effect. Lipopolysaccharide (LPS) injection in the intraoral mucosa resulted in facial heat hyperalgesia an increase in IL-1ß levels in the TG, which were reduced by systemic NTX. Stimulation of macrophages with LPS resulted in increase of nitric oxide, IL-1ß and CXCL-2 levels which were reduced by NTX. Altogether, these results provide evidence for an antinociceptive effect of ULDN in postoperative orofacial pain and suggest that blockade of TLR4 and downstream signaling pathway contribute to its effect.

Antinociceptive effects of bupivacaine and its sulfobutylether-ß-cyclodextrin inclusion complex in orofacial pain.

Bupivacaine hydrochloride (BVC) represents an option to produce long-lasting analgesia, and complexation in cyclodextrins has shown improvements in biopharmaceutical properties. This study aimed to characterize and test the cytotoxicity and antinociceptive effects of BVC complexed in sulfobutylether-ß-cyclodextrin (SBEßCD). The kinetics and stoichiometry of complexation and BVC-SBEßCD association constant were evaluated by phase solubility study and Job's plot. Evidence of the BVC-SBEßCD complex formation was obtained from scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The cytotoxicity was evaluated in keratinocyte (HaCaT) and neuroblastoma (SH-SY5Y). Antinociceptive effects were registered via orofacial pain models: the formalin test, carrageenan-induced hyperalgesia, and postoperative pain (intraoral incision). The complex formation occurred at a 1:1 BVC-SBEßCD molar ratio, with a low association constant (13.2 M-1). SEM, DSC, and FTIR results demonstrated the host-guest interaction. The IC50% values determined in SH-SY5Y were 216 µM and 149 µM for BVC and BVC-SBEßCD, respectively (p < 0.05). There was no difference in HaCaT IC50%. In orofacial pain model, BVC-SBEßCD significantly prolonged antinociceptive effect, in about 2 h, compared to plain BVC. SBEßCD can be used as a drug delivery system for bupivacaine, whereas the complex showed long-lasting analgesic effects.

Trigeminal Schwannoma simulating orofacial pain: differential diagnosis and treatment. Case report / Schwannoma trigeminal simulando dor orofacial: diagnóstico diferencial e tratamento. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Orofacial pain is a major diagnostic challenge for the most experienced clinicians. Due to the complexity regarding the trigeminal-cervical joint, orofacial pain with the same etiology may present different symptoms, and pain with similar symptomatology may have different causes. The objective of this study was to alert health professionals about the importance of differential diagnosis in the hypothesis of trigeminal neuralgia, where the inclusion of the dentist in the medical-hospital team is of paramount importance in establishing the correct diagnosis. CASE REPORT: Twenty-nine-year-old female patient complained of electric shock and pulsatile orofacial pain that covered the third division of the fifth cranial nerve on the right side. Magnetic resonance imaging revealed the presence of trigeminal Schwannoma, causing neuralgia due to its neural compressive nature. Two different neurosurgery departments suggested tumor resection. However, after the evaluation by a third neurosurgery department, in which a dentist, specialized in orofacial pain was part of the team, the complete evaluation established the final diagnosis of right lower first molar odontalgia, with irreversible acute pulpitis as the cause of the symptoms and the expansive lesion was only a radiological finding. CONCLUSION: Interdisciplinary evaluation among physicians and dental surgeons is necessary to obtain the correct diagnosis when considering the hypothesis of trigeminal neuralgia.

RESUMO JUSTIFICATIVA E OBJETIVOS: As dores orofaciais representam grande desafio diagnóstico ao mais experiente clínico. Devido à complexidade do conjunto trigeminocervical, as dores orofaciais com a mesma etiologia podem apresentar sintomas diferentes, e dores com o mesmo sintoma podem ter etiologias diferentes. O objetivo foi alertar o profissional da saúde sobre a importância do diagnóstico diferencial quando aventada a hipótese diagnóstica de neuralgia trigeminal, e a presença do cirurgião-dentista na equipe médico-hospitalar é de suma importância para o estabelecimento do diagnóstico. RELATO DO CASO: Paciente do sexo feminino, 29 anos, apresentou dor orofacial em choque elétrico e pulsátil que percorria o trajeto da terceira divisão do V par craniano, do lado direito. A ressonância nuclear magnética evidenciou Schwannoma trigeminal, sendo diagnosticada neuralgia trigeminal secundária à essa lesão expansiva. Foi sugerida ressecção tumoral em dois serviços de neurocirurgia. Contudo, após a avaliação de um terceiro serviço de neurocirurgia, com a participação de cirurgião-dentista especialista em dor orofacial, foi estabelecido o diagnóstico de odontalgia do primeiro molar inferior direito, com pulpite aguda irreversível, sendo essa a causa do quadro sintomático, e a lesão expansiva, apenas um achado radiológico. CONCLUSÃO: A avaliação interdisciplinar entre médicos e cirurgiões-dentistas é necessária para o diagnóstico correto quando a hipótese diagnóstica for neuralgia trigeminal.

Use of viminol in acute pain management after third molars extraction. Case report / Uso do viminol no controle da dor aguda pós-extração de terceiros molares. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Acute postoperative pain of the third molars requires not only the ability of the dental surgeon in removing them but also the correct pharmacological control of this incidental pain that will install after the effect of the anesthetic blockade has ceased. The objective of this study was to report a case of moderate pain after third molar removal procedure, where the adverse effects of the prescribed medication were determinant for the abandonment of pharmacological treatment and consequently the maintenance of the pain. CASE REPORT: A 22-year-old male patient, student, from the city of Curitiba, sought outpatient care for acute moderate-intensity pain after 48 hours of removal of the third molars. He was experiencing some adverse effects due to the prescription of the combination of oral codeine (30mg) and paracetamol (325mg) at every 6 hours. In view of this, we opted for the prescription of viminol hydroxybenzoate (70mg) orally, every 6 hours. CONCLUSION: The prescription of the viminol hydroxybenzoate analgesic resulted in complete, rapid and effective postoperative analgesia, with excellent tolerability.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor aguda pós-operatória de terceiros molares requer não somente habilidade do cirurgião-dentista em removê-los, mas também no correto controle farmacológico desse quadro álgico que se instalará após o efeito do bloqueio anestésico ter cessado. O objetivo deste estudo foi relatar um caso de dor moderada pós-procedimento de remoção de terceiros molares, em que os efeitos adversos do fármaco prescrito foram determinantes para o abandono do tratamento farmacológico e consequentemente da manutenção da dor. RELATO DO CASO: Paciente do sexo masculino, 22 anos, estudante, natural de Curitiba, procurou atendimento ambulatorial por queixa de dor aguda de moderada intensidade, após 48 horas da remoção dos terceiros molares. Apresentou efeitos adversos devido à prescrição da associação de codeína (30mg) e paracetamol (325mg) por via oral de 6/6 horas. Frente a isso, optou-se pela prescrição de hidroxibenzoato de viminol (70mg) por via oral de 6/6 horas. CONCLUSÃO: A prescrição do analgésico hidroxibenzoato de viminol resultou em completa, rápida e eficaz analgesia pós-operatória, com excelente tolerabilidade.

Tinnitus and temporomandibular disorders: the knowledge of professionals for primary health care in the city of Curitiba.

INTRODUCTION: The high prevalence of temporomandibular disorders and tinnitus along with the negative effects on the quality of life of affected individuals makes this association a matter of public health. OBJECTIVE: To assess the knowledge of primary health care professionals about the interrelationship between temporomandibular disorders and tinnitus. MATERIALS AND METHODS: This was a quantitative cross-sectional study, using a structured, self-administered questionnaire for a group of 54 dental surgeons. The statistical analysis used involved descriptive analyses through absolute and relative frequency distributions. RESULTS: The results showed that the professionals do not, as a routine, examine the temporomandibular joints and masticatory muscles during physical examination. In addition, there was a low percentage of correct answers on questions that assess knowledge. CONCLUSIONS: There is a need to inform dentists about the interrelationship between temporomandibular disorders and tinnitus. Furthermore, there is a need to encourage managers to establish teaching and learning tools that support and strengthen the role of dentists in primary health care. In this way, routine visits might minimize these disorders, and thus contribute to the quality of life of the population.

Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

AIMS: To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. METHODS: Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. RESULTS: Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. CONCLUSION: Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

Clinical aspects and pharmacological treatment of trigeminal neuralgia

Introduction: Trigeminal neuralgia (TN) is defined as sudden, usually unilateral, severe and brief pain episodes within the distribution of one or more branches of the trigeminal nerve. In some patients a constant background pain may persist, additionally to pain attacks, which can make difficult to differentiate the trigeminal neuralgia from other orofacial pain types. Objective: To review the classification, physiopathological aspects, epidemiologic data and pharmacological options to control pain related to trigeminal neuralgia. Literature review: One of the proposed etiologies for this condition is a localcircumscribed demyelination of the trigeminal nerve resulting in neuronal hyperexcitability and generation of ephaptic coupling, which would be responsible for the pain paroxysms. Initially, the treatment of patients with these pain characteristics is based on the use of anticonvulsants, in order to attenuate the ectopic-generated pain impulses. Carbamazepine is the first-line drug, but other anticonvulsants may be employed and have shown variable efficacy in the treatment of trigeminal neuralgia. Conclusion: According to the new classification of the International Headache Society, classic trigeminal neuralgia is divided in purely paroxysmal and with concomitant persistent facial pain. The pathophysiology is unclear, but trigeminal neuralgia seems to be the consequence of vascular compression of the trigeminal nerve near the brain stem. Although TN presents a low prevalence in general population (i.e. 5-30 new patients per 100,000), trigeminal neuralgia is an important clinical concern both by pain severity and difficulty of its satisfactory control. Anticonvulsants are the medication of choice in the treatment of trigeminal neuralgia; however, their use is associated with several adverse effects and possibility of treatment refractoriness.

Chronic pain related to quality of sleep.

OBJECTIVE: To determine the relation between the degrees of chronic pain and drowsiness levels. METHODS: The study was conducted with 115 patients, who answered the questionnaire as diagnostic criteria in the survey. After evaluation based on the protocol of chronic pain registry RDC/TMD- Axis II, the Epworth Sleepiness Scale was applied to assess drowsiness levels. RESULTS: Among the participating patients, there were more females (80%), and the type of pain more prevalent was chronic (70.4%). Concerning the grades of chronic pain, grade II predominated (38.3%), corresponding to high pain intensity and low disability. The ratio observed for levels of sleepiness was more prevalent for sleep debt average (38.3%). CONCLUSION: The grades of chronic pain and the levels of sleepiness did not correlate with each other or with the gender of patients.

Chronic pain related to quality of sleep / Dor crônica relacionada à qualidade do sono

Objective To determine the relation between the degrees of chronic pain and drowsiness levels. Methods The study was conducted with 115 patients, who answered the questionnaire as diagnostic criteria in the survey. After evaluation based on the protocol of chronic pain registry RDC/TMD− Axis II, the Epworth Sleepiness Scale was applied to assess drowsiness levels. Results Among the participating patients, there were more females (80%), and the type of pain more prevalent was chronic (70.4%). Concerning the grades of chronic pain, grade II predominated (38.3%), corresponding to high pain intensity and low disability. The ratio observed for levels of sleepiness was more prevalent for sleep debt average (38.3%). Conclusion The grades of chronic pain and the levels of sleepiness did not correlate with each other or with the gender of patients. .

Objetivo Determinar a relação entre os graus de dor crônica e os níveis de sonolência. Métodos Participaram 115 pacientes que responderam ao questionário usado como critério diagnóstico na pesquisa. Após avaliação segundo protocolo de registro de dor crônica RDC/TMD − Eixo II, aplicou-se a Escala de Sonolência de Epworth para verificar os níveis de sonolência. Resultados Dentre os pacientes participantes havia mais mulheres (80%) e o tipo de dor mais prevalente era crônica (70,4%). Na relação dos graus de dor crônica, predominou o grau II (38,3%), correspondente à alta intensidade de dor e baixa incapacidade. A proporção observada para os níveis de sonolência mostrou maior prevalência para o débito de sono médio (38,3%). Conclusão Os graus de dor crônica e níveis de sonolência não apresentam correlação entre si, nem com o gênero dos pacientes. .

A importância da avaliação da presença de disfunção temporomandibular em pacientes com dor crônica / Importance of evaluating the presence of temporomandibular disorders in chronic pain patients

Justificativa e objetivos:Pacientes com dor crônica apresentam um menor limiar à dor apresentando dessa forma dores em outras topografias. O objetivo deste estudo foi avaliar a presença de disfunção temporomandibular em pacientes com dor crônica em diversas partes do corpo comparando com um grupo controle sem sintomatologia dolorosa. Além disso, buscou-se verificar qual dos grupos apresentou mais sintomas de disfunção temporomandibular e alteração miofascial nos músculos da mastigação. Métodos: A amostra foi composta por 180 indivíduos, divididos em 2 grupos, sendo 90 pacientes com dor crônica em diversas partes do corpo: grupo estudo, e 90 pacientes sem sintomatologia dolorosa: grupo controle. Para o diagnóstico da sintomatologia de disfunção temporomandibular foi utilizado o questionário proposto pela Academia Americana de Dor Orofacial. Foi realizada uma avaliação física dirigida e validada. Análises foram feitas para verificar a frequência de sintoma de disfunção temporomandibular tanto no grupo controle quanto no grupo estudo e a presença de disfunção temporomandibular muscular em ambos os grupos. Resultados: Entre os pacientes com dor crônica 70% apresentaram sintomatologia para disfunção temporomandibular e no grupo controle 55%. Os pacientes que apresentaram sintomatologia foram avaliados fisicamente e constatou-se que 45% apresentaram dor miofascial nos músculos da mastigação, contra 28% no grupo controle. Conclusão: A presença de sintomatologia de disfunção temporomandibular e dor muscular nos músculos da mastigação foi maior em pacientes com dor crônica em relação ao grupo controle e deve ser levada em consideração quando se propõe avaliar e controlar todas as dores nesses pacientes.

Background and objectives:Chronic pain patients have lower pain threshold, thus having pain in other parts of the body. This study aimed at evaluating the presence of temporomandibular disorders in patients with chronic pain in different parts of the body comparing them to a pain-free control group. In addition, we tried to determine which group had more temporomandibular disorder symptoms and myofascial changes in masticatory muscles. Methods: Sample was made up of 180 individuals divided in 2 groups, being 90 patients with chronic pain in different parts of the body: study group, and 90 pain-free patients: control group. The questionnaire proposed by the American Academy of Orofacial Pain was used to diagnose temporomandibular disorder symptoms. A directed and validated physical evaluation was performed. Analyses were done to determine the frequency of temporomandibular symptoms both in the control group and the study group, and the presence of muscular temporomandibular disorders in both groups. Results: Among chronic pain patients, 70% had temporomandibular disorder symptoms and in the control group they were 55%. Patients with symptoms were physically evaluated and it was observed that 45% had masticatory muscles myofascial pain as compared to 28% in the control group. Conclusion: The prevalence of temporomandibular disorder symptoms and masticatory muscles pain was higher among chronic pain patients as compared to the control group and should be taken into consideration when the proposal is to evaluate and control all pains of such patients.