The use of tricyclic antidepressants in the treatment of temporomandibular joint disorders: systematic review of the literature of the last 20 years

Many therapies have been proposed for the management of temporomandibular disorders, including the use of different drugs. However, lack of knowledge about the mechanisms behind the pain associated with this pathology, and the fact that the studies carried out so far use highly disparate patient selection criteria, mean that results on the effectiveness of the different medications are inconclusive. This study makes a systematic review of the literature published on the use of tricyclic antidepressants for the treatment of temporomandibular disorders, using the SORT criteria (Strength of recommendation taxonomy) to consider the level of scientific evidence of the different studies. Following analysis of the articles, and in function of their scientific quality, a type B recommendation is given in favor of the use of tricyclic antidepressants for the treatment of temporomandibular disorders.

Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation

Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs). This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs). TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs), have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX). TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test) and infiltration of polymorphonuclear neutrophils into the synovial fluid (myeloperoxidase enzyme quantification). MMP expression in the trigeminal ganglion was shown to vary during the phases of the inflammatory process. MMP-9 regulated the early phase and MMP-2 participated in the late phase of this process. Furthermore, increases in plasma extravasation in periarticular tissue and myeloperoxidase activity in the joint tissue, which occurred throughout the inflammation process, were diminished by treatment with DOX, a nonspecific MMP inhibitor. Additionally, the increases of mechanical allodynia and orofacial hyperalgesia were attenuated by the same treatment.

PAR(2) and Temporomandibular Joint Inflammation in the Rat

The proteinase-activated receptor 2 (PAR(2)) is a putative therapeutic target for arthritis. We hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (TMJ) are mediated by neurogenic mechanisms. Immunofluorescence analysis revealed a high degree of neurons expressing PAR(2) in retrogradely labeled trigeminal ganglion neurons. Furthermore, PAR(2) immunoreactivity was observed in the lining layer of the TMJ, co-localizing with the neuronal marker PGP9.5 and substance-P-containing peripheral sensory nerve fibers. The intra-articular injection of PAR(2) agonists into the TMJ triggered a dose-dependent increase in plasma extravasation, neutrophil influx, and induction of mechanical allodynia. The pharmacological blockade of natural killer 1 (NK(1)) receptors abolished PAR(2)-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. We conclude that PAR(2) activation is proinflammatory in the TMJ, through a neurogenic mechanism involving NK(1) receptors. This suggests that PAR(2) is an important component of innate neuro-immune response in the rat TMJ.

Putative antinociceptive action of nitric oxide in the caudal part of the spinal trigeminal nucleus during chronic carrageenan-induced arthritis in the rat temporomandibular joint

In order to investigate a putative role for nitric oxide (NO) in the central nociceptive processing following carrageenan-induced arthritis in the rat temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression and activity of nitric oxide synthases (NOS) in the caudal part of the spinal trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic-active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal threshold was carried out in all phases of arthritis under chronic inhibition of nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C, showing no significant statistical difference during arthritis. Only a discrete percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression for both nNOS and endothelial nitric oxide synthases (eNOS) presented no noticeable differences among the groups. No expression of inducible nitric oxide synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or reverse-transcription polymerase chain reaction (RTPCR). Ca(2+)-dependent NOS activity in the ipsilateral Sp5C was significantly higher (108.3 +/- 49.2%; P<0.01) in animals during the chronic arthritis. Interestingly, this increased activity was completely abolished 24 h later, in the chronic-active arthritis. Finally, head-withdrawal threshold decreased significantly in the chronic arthritis in animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its activity significantly increases in the chronic-phases supporting an antinociceptive role of the nNOS as evidenced by pain threshold experiment. (C) 2009 Elsevier B.V. All rights reserved.

Participation of peripheral tachykinin NK(1) receptors in the carrageenan-induced inflammation of the rat temporomandibular joint

Temporomandibular disorders represent one of the major challenges in dentistry therapeutics. This study was undertaken to evaluate the time course of carrageenan-induced inflammation in the rat temporomandibular joint (TMJ) and to investigate the role of tachykinin NK(1) receptors. Inflammation was induced by a single intra-articular (i.art.) injection of carrageenan into the left TMJ (control group received sterile saline). Inflammatory parameters such as plasma extravasation, leukocyte influx and mechanical allodynia (measured as the head-withdrawal force threshold) and TNF alpha and IL-1 beta concentrations were measured in the TMJ lavages at selected time-points. The carrageenan-induced responses were also evaluated after treatment with the NK(1) receptor antagonist SR140333. The i.art. injection of carrageenan into the TMJ caused a time-dependent plasma extravasation associated with mechanical allodynia, and a marked neutrophil accumulation between 4 and 24 h. Treatment with SR140333 substantially inhibited the increase in plasma extravasation and leukocyte influx at 4 and 24 h, as well as the production of TNF alpha and IL-1 beta into the joint cavity, but failed to affect changes in head-withdrawal threshold. The results obtained from the present TMJ-arthritis model provide, for the first time, information regarding the time course of this experimental inflammatory process. In addition, our data show that peripheral NK(1) receptors mediate the production of both TNF alpha and IL-1 beta in the TMJ as well as some of the inflammatory signs, such as plasma extravasation and leukocyte influx, but not the nociceptive component. 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.

Origin of sensory and autonomic innervation of the rat temporomandibular joint: A retrograde axonal tracing study with the fluorescent dye fast blue

Previous studies that have used retrograde axonal tracers (horseradish peroxidase alone or conjugated with wheat germ agglutinin) have shown that the temporomandibular joint (TMJ) is supplied with nerve fibers originating mainly from the trigeminal ganglion, in addition to other sensory and sympathetic ganglia. The existence of nerve fibers in the TMJ originating from the trigeminal mesencephalic nucleus is unclear, and the possible innervation by parasympathetic nerve fibers has not been determined. In the present work, the retrograde axonal tracer, fast blue, was used to elucidate these questions and re-evaluated the literature data. The tracer was deposited in the supradiscal articular space of the rat TMJ, and an extensive morphometric analysis was performed of the labeled perikaryal profiles located in sensory and autonomic ganglia. This methodology permitted us to observe labeled small perikaryal profiles in the trigeminal ganglion, clustered mainly in the posterior-lateral region of the dorsal, medial and ventral thirds of horizontal sections, with some located in the anterior-lateral region of the ventral third. Sensory perikarya were also labeled in the dorsal root ganglia from C2 to C5. No labeled perikaryal profiles were found in the trigeminal mesencephalic nucleus. on the other hand, autonomic labeled perikaryal profiles were distributed in the sympathetic superior cervical and stellate ganglia, and parasympathetic otic ganglion. Our results confirmed those of previous studies and also demonstrated that: (i) there is a distribution pattern of labeled perikaryal profiles in the trigeminal ganglion; (ii) some perikaryal profiles located in the otic ganglion were labeled; and (iii) the trigeminal mesencephalic nucleus did not show any retrogradely labeled perikaryal profiles.

PAR(2) and Temporomandibular Joint Inflammation in the Rat

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Putative antinociceptive action of nitric oxide in the caudal part of the spinal trigeminal nucleus during chronic carrageenan-induced arthritis in the rat temporomandibular joint

In order to investigate a putative role for nitric oxide (NO) in the central nociceptive processing following carrageenan-induced arthritis in the rat temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression and activity of nitric oxide synthases (NOS) in the caudal part of the spinal trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic-active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal threshold was carried out in all phases of arthritis under chronic inhibition of nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C, showing no significant statistical difference during arthritis. Only a discrete percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression for both nNOS and endothelial nitric oxide synthases (eNOS) presented no noticeable differences among the groups. No expression of inducible nitric oxide synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or reverse-transcription polymerase chain reaction (RTPCR). Ca(2+)-dependent NOS activity in the ipsilateral Sp5C was significantly higher (108.3 +/- 49.2%; P<0.01) in animals during the chronic arthritis. Interestingly, this increased activity was completely abolished 24 h later, in the chronic-active arthritis. Finally, head-withdrawal threshold decreased significantly in the chronic arthritis in animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its activity significantly increases in the chronic-phases supporting an antinociceptive role of the nNOS as evidenced by pain threshold experiment. (C) 2009 Elsevier B.V. All rights reserved.

Phenotypic alterations of neuropeptide Y and calcitonin gene-related peptide-containing neurons innervating the rat temporomandibular joint during carrageenan-induced arthritis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Temporomandibular Joint Vibration Before and After Exercises and Occlusal Splints

Temporomandibular joint (TMJ) sounds are frequent in patients. The aim of this study was to analyze patients with clicking at the end of opening and at the beginning of closing their mouths treated by muscular exercises through chewing and by occlusal splints. Fifteen patients with clinically verified clicking and TMJ and 15 patients without sounds were selected by the Research Diagnostic Criteria for Temporomandibular Disorders. They were submitted to electrovibratography at consultation and 60 and 120 days of treatment by occlusal splints and exercises. Patients demonstrated significant reduction of TMJ sounds after treatment, but vibration intensity was not similar with that of the control group after 120 days.

Study About the Development of the Temporomandibular Joint in the Human Fetuses

The temporomandibular joint (TMJ) is a highly specialized articulation that differs from all the other synovial articulations for many reasons. In children, different from what we observe in adults, these articulations have rarely been studied under the morphofunctional aspect, mainly in the embryonary and fetal stages. In this study 10 fetuses with ages varying from 16 to 39 weeks of intrauterine life were used, and it could be observed that the fibers and thickness of the articular disc, as well as the articular capsule and the condylar process, suffer modifications according to age. It was also observed that the superior head of the lateral pterygoid muscle inserts itself in the articular disc and capsule in all the ages studied. Also, the maturation of the articular tissues, especially of the articular disc, as well as, the associated muscles, suggests that the TMJ was able to carry out mandibular movements since the 24(th) week of intrauterine life.

Temporomandibular joint ankylosis and salivary mucocele in a cat: case report

Relata-se o caso de um gato de aproximadamente um ano e meio de idade, macho, não castrado, que foi encaminhado por apresentar incapacidade de abrir a boca e aumento de volume flutuante na região intermandibular. As lesões estavam presentes há um ano, desde quando o gato foi encontrado e adotado. A causa não foi determinada. Baseado nos exames físicos e radiográficos diagnosticou-se anquilose da articulação temporomandibular esquerda e mucocele salivar. O aspecto lateral do processo condilar da mandíbula esquerda foi removido, e a mucocele foi tratada por ressecção das glândulas salivares mandibular e sublingual direita e por drenagem da mucocele. Após a cirurgia, o gato mostrou bom uso funcional da mandíbula, sem sinais de desconforto.