Participação dos receptores opioides capa perifericos na modulação da resposta nociceptiva induzida pela administração de formalina na ATM de ratos de diferentes sexos e fases do ciclo estral

Orientadores: Claudia Herrera Tambeli, Maria Cecilia F. A. VeigaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Este estudo avaliou as diferenças sexuais na resposta nociceptiva induzida pela administração de formalina na articulação temporomandibular (ATM) com ou sem a co-administração do U50,488 (agonista do receptor opióide capa). As fases do ciclo estral das fêmeas foram citologicamente determinadas e apenas aquelas que apresentavam-se na fase diestro ou proestro, e machos foram incluídos. A formalina induziu um comportamento nociceptivo maior nas fêmeas em diestro do que nas fêmeas em proestro ou machos. O U50,488 reduziu significativamente as respostas nociceptivas induzidas pela formalina, e esta redução foi maior nas fêmeas, especialmente nas fêmeas da fase diestro do ciclo estral. A injeção do U50,488 na ATM contralateral não afetou na magnitude do comportamento induzido pela formalina, e o pré-tratamento com o antagonista seletivo do receptor opióide capa nor-binaltorphimine (norBNI) na ATM ipsilateral reduziu os efeitos antinociceptivos do U50,488. Estes resultados demonstram a ação dos receptores opióides capa periféricos na modulação da dor inflamatória. Além disso, considerando que os níveis plasmáticos dos hormônios ovarianos são baixos durante a fase diestro, estes resultados são consistentes com a hipótese de que os hormônios sexuais femininos podem ter uma ação analgésica na redução da dor inflamatória induzida pela formalina, assim como, também ter uma ação anti-analgésica nos efeitos mediados pelos receptores opióides capaAbstract: This study examined sex differences in nociceptive responses induced by intra-temporomandibular joint (TMJ) formalin with and without co-administration of the ?-opioid receptor agonist U50,488. The estrous phase of females was cytologically determined; only those in either proestrus or diestrus, and males, were included. Formalin elicited significantly greater nociceptive behavior in diestrus females than in either proestrus females or males. U50,488 significantly reduced formalin nociceptive responses, and this reduction was significantly greater in females, especially in the diestrus phase of the estrous cycle. U50,488 injection into the contralateral TMJ failed to affect the magnitude of formalininduced behavior, and preinjection of the selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) into the ipsilateral TMJ significantly reduced the antinociceptive effect of U50,488. These findings support a role for peripheral kappa-opioid receptors in the modulation of inflammatory pain. Furthermore, since plasma levels of ovarian hormones are lowest during diestrus, these findings are consistent with the suggestion that female sex hormones may play an analgesic role in reducing formalin-induced inflammatory pain, and may also play an anti-analgesic role, at least in ?-mediated effectsMestradoFisiologia OralMestre em Odontologi

Evaluation of mechanisms involved in a sexual dimorphism of analgesia mediated by kappa opioid receptor in temporomandibular joint

Orientador: Claudia Herrera TambeliTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Recentemente foi demonstrado que a ativação de receptores capa opióides localizados na ATM de ratos reduz o comportamento nociceptivo induzido pela injeção se formalina na ATM de ratos, especialmente nas fêmeas na fase diestro do ciclo estral. Sendo a fase diestro aquela que representa baixos níveis hormonais, estes resultados indicam que os hormônios gonadais diminuem a antinocicepção mediada pelos receptores capa na ATM. O objetivo deste trabalho foi investigar o possível mecanismo pelo qual os hormônios gonadais poderiam diminuir a antinocicepção mediada pelos receptores capa opióides através das seguintes hipóteses: (a) Os hormônios gonadais diminuem a antinocicepção mediada pelos receptores capa na ATM por diminuírem a expressão de receptores capa opióides no gânglio trigeminal; (b) O efeito periférico antinociceptivo dos agonistas dos receptores capa opióides é mediado pela ativação da via L-Arginina/NO/GMPc em machos e fêmeas; (c) Os hormônios gonadais diminuem a antinocicepção mediada pelos receptores capa na ATM por diminuírem a ativação da via L-Arginina/NO/GMPc. A análise pela técnica Western blot demonstrou que a expressão protéica dos receptores capa opióides é maior em fêmeas do que em machos, sugerindo que a testosterona induz acentuada diminuição na expressão dos receptores capa opióides. Nas fêmeas, a expressão dos receptores capa opióides foi significativamente maior nas fêmeas em diestro em relação às fêmeas em proestro, sugerindo que os hormônios gonadais femininos também diminuem a expressão dos receptores capa opióides. A co-administração do inibidor da NO-sintase, L-NMMA, ou do inibidor da guanilil ciclase sensível ao NO, ODQ, com o agonista do receptor capa opióide U50,488 bloqueou a antinocicepção mediada pelos receptores capa na ATM de machos e fêmeas, sugerindo que a antinocicepção induzida pelos receptores capa opióides é mediada pela ativação da via L-Arginina/NO/GMPc em ambos os sexos. No entanto, a co-administração de baixas doses de L-NMMA e ODQ com U50,488 significativamente diminuiu a antinocicepção mediada por receptores capa apenas nas fêmeas em diestro. Estes resultados indicam que a antinocicepção mediada pelos receptores capa opióides depende da ativação da via L-Arginina/NO/GMPc em machos e fêmeas. No entanto, o dimorfismo sexual na antinocicepção mediada pelos receptores capa opióides na ATM se deve, pelo menos em parte, pela diminuição da expressão dos receptores capa opióides no gânglio trigeminal pelos hormônios gonadais, especialmente a testosterona. Apesar do envolvimento da via L-Arginin/NO/GMPc na antinocicepção mediada pelo receptor capa na ATM em ambos os sexos, os hormônios gonadais não diminuem a atividade desta via diminuindo o efeito antinociceptivo mediado por receptores capa opióides na ATMAbstract: We have previously demonstrated that activation of kappa opioid receptors located in the TMJ of rats suppresses formalin-induced TMJ nociception behavior especially in females of the diestrus phase of the estrous cycle. Since diestrus is a phase of low gonadal hormonal serum level, these findings indicate that gonadal hormones decrease kappa-mediated TMJ antinociception. The aim of this study was to investigate some of the mechanisms by which gonadal hormones might decrease kappa-mediated antinociception by testing the following hypothesis: (a) Gonadal hormones decrease kappa-mediated TMJ antinociception through a down regulation in the expression of kappa oipoid receptors in the trigeminal ganglia; (b) The peripheral antinociceptive effect of kappa opioid receptor agonists is mediate by the activation of the L-Arginine/NO/cGMP pathway in both males and females; (c) Gonadal hormones decrease kappa-mediated TMJ antinociception by diminishing the activity of the L-Arginine/NO/cGMP. Western blot analysis demonstrated that protein expression of KORs was significantly higher in females than in males, suggesting that testosterone induces a strong down-regulation in KOR expression. In females, KOR expression was significantly higher in those in diestrus than in proestrus suggesting that female gonadal hormones also down-regulate KOR expression in the trigeminal ganglia. Co-application of the NOS inhibitor L-NMMA or of the NO-sensitive guanylyl cyclase inhibitor ODQ with the kappa opioid receptor agonist U50,488 blocked kappa-mediated TMJ antinociception in males and females suggesting that antinociception induced by activation of peripheral kappa opioid receptors is mediated by the L-arginine/NO/cGMP pathway in both sexes. However, co-application of lower doses of L-NMMA and ODQ with U50,488 significantly diminished kappa -mediated TMJ antinociception only in diestrus females. These results indicate that kappa-mediated TMJ antinociception depends on activation of the L-Arginine/NO/cGMP pathway in both males and females. However, the sexual dimorphism in kappa-mediated TMJ antinociception is mediated, at least in part, by the down regulation in the expression of kappa-oipoid receptors in the trigeminal ganglia induced by gonadal hormones, especially testosterone. Despite the involvement of the L-Arginine/NO/cGMP pathway in kappa-mediated TMJ antinociception in both sexes, gonadal hormones do not diminish the activity of this pathway to decrease kappa-mediated TMJ antinociceptionDoutoradoFisiologia OralDoutor em Odontologi

Histological and mast cells evaluation after application of botulinum toxin type a in masseter muscles of rats

Botulinum Toxin Type A (BTX-A) has been largely used to reduce muscle strength of masseter and temporal muscles by producing a temporary weakening of their activity. This study aimed to evaluate the histological changes and the number of mast cells afte

Remodeling of gingival contour in the rehabilitation with fixed partial dentures – case report / Remodelação do contorno gengival em reabilitação com prótese parcial fixa – relato de caso

One of the most challenging aspects in rehabilitations is the correct manipulation of gingival tissues, aiming to achieve a natural contour, with interdental papillae and emergence profile, compatible with a natural tooth. The rehabilitation is impaired when there is loss of the interproximal papilla. To solve this problem, it is possible to use the gingival conditioning technique, which comprises relining the provisional crown with acrylic resin, applying gradual pressure, leading to formation of a gingival papilla. This paper presents a case of esthetic and functional recovery in a fixed partial denture by remodeling of the gingival contour by the gradual pressure technique, by gradual relining of the provisional crown. It is concluded that this gingival conditioning technique is simple, easy to accomplish and very effective for esthetic-functional reestablishment in rehabilitations with fixed partial dentures, provided the patient maintains correct hygiene and plaque control. 

15d-PGJ(2)-loaded solid lipid nanoparticles: physicochemical characterization and evaluation of pharmacological effects on inflammation

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ(2)-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ(2)-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ(2)-SLN at concentrations of 3, 10 or 30 mu g.kg(-1) before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1 beta, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ(2)-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ(2)-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ(2). Additionally, 15d-PGJ(2)-SLN increased IL-10 levels and reduced IL-1 beta as well as IL-17 in peritoneal fluid. The new 15d-PGJ(2)-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ(2).15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ(2)-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ(2)-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ(2)-SLN at concentrations of 3, 10 or 30 mu g.kg(-1) before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1 beta, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ(2)-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ(2)-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ(2). Additionally, 15d-PGJ(2)-SLN increased IL-10 levels and reduced IL-1 beta as well as IL-17 in peritoneal fluid. The new 15d-PGJ(2)-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ(2)118e0161796FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2014/11016-8303555/2013-

Métodos de ensino em Fisiologia aplicados à geração Z: uma experiência voltada para os estudantes do primeiro ano de Medicina/ Teaching methods in Physiology applied to Generation Z: an experience aimed at first year medical students

A Educação Superior tem vivido uma grande transformação em vários campos do conhecimento, especialmente relacionado ao processo de ensino-aprendizagem. O rápido crescimento das novas tecnologias apresentam um importante desafio às antigas práticas e técnicas de ensino, principalmente devido as novas gerações possuírem acesso a uma ampla base de informações geradas em tempo real. Com isso, o objetivo da pesquisa foi desenvolver materiais de ensino complementares (texto, podcast e cartilha), a fim de verificar suas contribuições no processo de ensino-aprendizagem na disciplina de Fisiologia aos estudantes ingressantes do curso de Medicina. Para tanto, realizou-se um estudo observacional descritivo, que foi desenvolvido através de um questionário estruturado e aplicado após a aula expositiva e ao acesso ao material, de acordo com os diferentes estilos de aprendizagem. Os resultados obtidos permitem levantar considerações sobre as vantagens de se aplicar métodos complementares de ensino, pois apresentam-se no processo de ensino-aprendizagem, como facilitadores na apropriação do conhecimento compartilhado no ambiente educacional. Além disso, permite que o estudante seja um agente co-participativo da sua formação acadêmica conferindo-lhe autonomia durante o seu desenvolvimento profissional

Orofacial musculoskeletal pain: An evidence-based bio-psycho-social matrix model

Pain is a multidimensional experience comprising sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Clinical and research findings have demonstrated a complex interplay between social burdens, individual coping strategies, mood states, psychological disorders, sleep disturbances, masticatory muscle tone, and orofacial musculoskeletal pain. Accordingly, current classification systems for orofacial pain require psychosocial assessments to be an integral part of the multidimensional diagnostic process. Here, we review evidence on how psychosocial and biological factors may generate and perpetuate musculoskeletal orofacial pain. Specifically, we discuss studies investigating a putative causal relationship between stress, bruxism, and pain in the masticatory system. We present findings that attribute brain structures various roles in modulating pain perception and pain-related behavior. We also examine studies investigating how the nervous and immune system on cellular and molecular levels may account for orofacial nociceptive signaling. Furthermore, we review evidence pointing towards associations between orofacial musculoskeletal pain and neuroendocrine imbalances, sleep disturbances, and alterations of the circadian timing system. We conclude with several proposals that may help to alleviate orofacial pain in the future

Orofacial musculoskeletal pain : an evidence-based bio-psycho-social matrix model

© 2021 Published by Elsevier Ltd.Pain is a multidimensional experience comprising sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Clinical and research findings have demonstrated a complex interplay between social burdens, individual coping strategies, mood states, psychological disorders, sleep disturbances, masticatory muscle tone, and orofacial musculoskeletal pain. Accordingly, current classification systems for orofacial pain require psychosocial assessments to be an integral part of the multidimensional diagnostic process. Here, we review evidence on how psychosocial and biological factors may generate and perpetuate musculoskeletal orofacial pain. Specifically, we discuss studies investigating a putative causal relationship between stress, bruxism, and pain in the masticatory system. We present findings that attribute brain structures various roles in modulating pain perception and pain-related behavior. We also examine studies investigating how the nervous and immune system on cellular and molecular levels may account for orofacial nociceptive signaling. Furthermore, we review evidence pointing towards associations between orofacial musculoskeletal pain and neuroendocrine imbalances, sleep disturbances, and alterations of the circadian timing system. We conclude with several proposals that may help to alleviate orofacial pain in the future.info:eu-repo/semantics/publishedVersio

Peripheral soluble epoxide hydrolase inhibition reduces hypernociception and inflammation in albumin-induced arthritis in temporomandibular joint of rats

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial tissue, joint dysfunction, and damage. Epoxyeicosatrienoic acids (EETs) are endogenous anti-inflammatory compounds, which are quickly converted by the soluble epoxide hydrolase (sEH) enzyme into a less active form with decreased biological effects. The inhibition of the sEH enzyme has been used as a strategy to lower nociception and inflammation. The goal of this study was to investigate whether the peripheral treatment with the sEH enzyme inhibitor 1- trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) could prevent the hypernociception and inflammation in the albumin-induced arthritis model in rats' temporomandibular joint (TMJ). After the induction of experimental arthritis, animals were assessed for nociceptive behavior test, leukocyte infiltration counts and histologic analysis, ELISA to quantify several cytokines and Western blotting. The peripheral pretreatment with TPPU inhibited the arthritis-induced TMJ hypernociception and leukocyte migration. Moreover, the local concentrations of proinflammatory cytokines were diminished by TPPU, while the anti-inflammatory cytokine interleukin-10 was up-regulated in the TMJ tissue. Finally, TPPU significantly decreased protein expression of iNOS, while did not alter the expression of MRC1. This study provides evidence that the peripheral administration of TPPU reduces hypernociception and inflammation in TMJ experimental arthritis