Laser therapy reduces gelatinolytic activity in the rat trigeminal ganglion during temporomandibular joint inflammation.

OBJECTIVES: To investigate whether low-level laser therapy (LLLT) alters the expression and activity of MMP-2 and MMP-9 in the trigeminal ganglion (TG) during different stages of temporomandibular joint (TMJ) inflammation in rats. It also evaluated whether LLLT modifies mechanical allodynia and orofacial hyperalgesia. MATERIALS AND METHODS: Wistar rats (±250 g) were divided into groups that received saline (SAL) or complete Freund's adjuvant (CFA, 50 µl) in the TMJ, and that later underwent LLLT (20 J cm(-2) ) at their TMJ or not (groups SAL, SAL + LLLT, CFA, and CFA + LLLT). LLLT was applied on days 3, 5, 7, and 9 after SAL or CFA. Mechanical allodynia was evaluated on days 1, 3, 5, 7, and 10; orofacial hyperalgesia was assessed on day 10. Gelatin zymography and in situ zymography aided quantification of MMPs in the TG. RESULTS: Low-level laser therapy abolished the reduction in the mechanical orofacial threshold and the increase in orofacial rubbing during the orofacial formalin test induced by CFA. LLLT also decreased the CFA-induced rise in the levels of MMP-9 and MMP-2 as well as the gelatinolytic activity in the TG. CONCLUSION: Low-level laser therapy could constitute an adjuvant therapy to treat temporomandibular disorders and prevent inflammation-induced alterations in the levels of MMP-2 and MMP-9 and in the gelatinolytic activity in TGs.

Upregulation of cystathionine-ß-synthetase expression contributes to inflammatory pain in rat temporomandibular joint.

BACKGROUND: Hydrogen sulfide (H2S), an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However, the role for H2S in nociceptive processing in trigeminal ganglion (TG) neuron remains unknown. The aim of this study was designed to investigate whether endogenous H2S synthesizing enzyme cystathionine-ß-synthetase (CBS) plays a role in inflammatory pain in temporomandibular joint (TMJ). METHODS: TMJ inflammatory pain was induced by injection of complete Freund's adjuvant (CFA) into TMJ of adult male rats. Von Frey filaments were used to examine pain behavioral responses in rats following injection of CFA or normal saline (NS). Whole cell patch clamp recordings were employed on acutely isolated TG neurons from rats 2 days after CFA injection. Western blot analysis was carried out to measure protein expression in TGs. RESULTS: Injection of CFA into TMJ produced a time dependent hyperalgesia as evidenced by reduced escape threshold in rats responding to VFF stimulation. The reduced escape threshold was partially reversed by injection of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, in a dose-dependent manner. CFA injection led to a marked upregulation of CBS expression when compared with age-matched controls. CFA injection enhanced neuronal excitability as evidenced by depolarization of resting membrane potentials, reduction in rheobase, and an increase in number of action potentials evoked by 2 and 3 times rheobase current stimulation and by a ramp current stimulation of TG neurons innervating the TMJ area. CFA injection also led to a reduction of IK but not IA current density of TG neurons. Application of AOAA in TMJ area reduced the production of H2S in TGs and reversed the enhanced neural hyperexcitability and increased the IK currents of TG neurons. CONCLUSION: These data together with our previous report indicate that endogenous H2S generating enzyme CBS plays an important role in TMJ inflammation, which is likely mediated by inhibition of IK currents, thus identifying a specific molecular mechanism underlying pain and sensitization in TMJ inflammation.

[Explanation of some physiological characteristics of homeostasis in elderly patients with temporomandibular joint dysfunction].

Most number of patients, particularly adult and older women with temporomandibular disfunction suffers from pain reaction in maxillofacial area. Pain symptom associated with temporomandibular disfunction is followed by some changes of physiological statistics (high sympathetic level). Temporomandibular disfunction in adult and older women is most pronounced and can serve as an indicator of concomitant chronic diseases among patients with endocrine disorder (hypothyroidism), cardiological pathology (arterial hypertension).

Auriculotemporal neuralgia secondary to TMJ synovial cyst: a rare presentation of a rare entity.

Synovial cysts of the temporomandibular joint are rare, and to our knowledge, only 14 cases have been reported. The most common presentation is local pain and swelling. We present a case of a synovial cyst presenting with neuralgia in the distribution of the auriculotemporal nerve, initially misdiagnosed as trigeminal neuralgia.

Effects of a liquid diet on the response properties of temporomandibular joint nociceptive neurons in the trigeminal subnucleus caudalis of growing rats.

OBJECTIVE: To investigate whether low mechanical loading on the temporomandibular joint (TMJ) when ingesting a liquid diet affects the response properties of neurons in the trigeminal spinal tract subnucleus caudalis (Sp5C) in growing rats. MATERIALS AND METHODS: Shortly after weaning, 2-week-old male rats were fed chow pellets (control) or a liquid diet (experimental). Firing activities of single sensory units were recorded from the Sp5C at 4, 5, 7, and 9 weeks. Neurons were functionally classified by their responsiveness to TMJ stimuli. The responses of Class II and III neurons to TMJ stimuli were investigated. RESULTS: In both neuron classes, the firing threshold in the experimental group was significantly lower than in the control group at all time points, but remained static in the control group throughout the experimental period, whereas it peaked in the experimental group at 4 weeks, decreased at 5 weeks, and remained stable thereafter until 9 weeks. Similarly, the initial firing frequency was significantly higher in the experimental group than in the control group, but remained static in the control group throughout the experimental period, whereas in the experimental group, it was at its lowest at 4 weeks, increased at 5 weeks, and stayed stable thereafter until 9 weeks. CONCLUSION: Differences in TMJ loading arising from variable diet consistency during growth may affect the functional characteristics of Sp5C neurons.

[Changes in ingestive behavior during growth affects the functional maturation of temporomandibular joint nociceptive neurons of rats].

Temporomandibular joint (TMJ) loading during development promotes its growth and maintains normal structure/function. Continuous change in diet consistency is related to development and maturation of the peripheral nervous system, including the nociceptive system. However, the functional modulation of TMJ-nociceptive neurons under different ingestive behavior is unclear. We fed growing rats a liquid diet to investigate the effects of low TMJ loading on the response properties of neurons in the trigeminal spinal tract subnucleus caudalis (Sp5C). Forty 2-week-old male rats were used. They were fed chow pellets (n = 20, C group) or a liquid diet (n = 20, LD group) soon after weaning. Firing activities of single sensory units in response to TMJ pressure stimuli were recorded at 4, 5, 7 and 9 weeks. In TMJ-nociceptive neurons, the firing threshold (FT) in the LD group was significantly lower than that in the C group at each recording age. The FT in the C group remained unchanged throughout the recording period, whereas that in the LD group was the highest at 4 weeks, and gradually decreased. On the other hand, the initial firing frequency (IFF) was significantly higher in the LD group than in the C group at each recording age. The IFF in the C group remained unchanged throughout the experimental period, whereas that in the LD group was at its lowest at 4 weeks, and gradually increased. Based on these findings, ingestive behavior that results from continuous changes in the physical consistency of the diet during growth may affect the functional maturation of TMJ-nociceptive neurons.

Response properties of temporomandibular joint mechanosensitive neurons in the trigeminal sensory complex of the rabbit.

The neurophysiological properties of neurons sensitive to TMJ movement (TMJ neurons) in the trigeminal sensory complex (Vcomp) during passive movement of the isolated condyle were examined in 46 rabbits. Discharges of TMJ neurons from the rostral part of the Vcomp were recorded with a microelectrode when the isolated condyle was moved manually and with a computer-regulated mechanostimulator. A total of 443 neurons responding to mechanical stimulation of the face and oral cavity were recorded from the brainstem. Twenty-one TMJ neurons were detected rostrocaudally from the dorsal part of the trigeminal principal sensory nucleus (NVsnpr), subnucleus oralis of the trigeminal spinal nucleus, and reticular formation surrounding the trigeminal motor nucleus. Most of the TMJ neurons were located in the dorso-rostral part of the NVsnpr. Of the TMJ units recorded, 90 % were slowly adapting and 26 % had an accompanying resting discharge. The majority (86 %) of the TMJ units responded to the movement of the isolated condyle in the anterior and/or ventral directions, and half were sensitive to the condyle movement in a single direction. The discharge frequencies of TMJ units increased as the condyle displacement and constant velocity (5 mm/s) increased within a 5-mm anterior displacement of the isolated condyle. Based on these results, we conclude that sensory information is processed by TMJ neurons encoding at least joint position and displacement in the physiological range of mandibular displacement.

CB1 and CB2 contribute to antinociceptive and anti-inflammatory effects of electroacupuncture on experimental arthritis of the rat temporomandibular joint.

Electroacupuncture (EA) and cannabinoids have been reported to have anti-inflammatory and antinociceptive effects in animal models of arthritis. Male Wistar rats were injected with saline or zymosan (2 mg) into the temporomandibular joint (TMJ). EA (10 Hz, 30 min) was performed 2 h after or 1 h before zymosan administration. AM251 or AM630 (3 mg/kg, i.p.)were administered before EA treatment. Mechanical hypernociception was accessed after zymosan administration. Rats were sacrificed 6 h after zymosan administration and the joint was removed for histopathological analysis. The gene expression of CB1 and CB2 receptors was assessed after sacrifice of the TMJ arthritic animals. EA inhibited zymosan-induced hypernociception (p < 0.05). AM251 reversed significantly the antinociceptive effect of EA, suggesting that the CB1 receptor is involved in this effect. AM630 reversed the anti-inflammatory effect of EA. CB1 and CB2 receptor gene expression was upregulated 6 h after zymosan-induced arthritis in the EA-treated group. We observed downregulation of CB2 receptor gene expression in the EA group at the 24th hour compared with the 6th hour. Higher CB1 receptor gene expression was also found compared with the 6th hour. EA produced antinociceptive and anti-inflammatory effects, and these effects appeared to be mediated through CB1 and CB2 receptor activation.

Participation of microglial p38 MAPK in formalin-induced temporomandibular joint nociception in rats.

AIMS: To investigate nociceptive behavior and the immunoreactivity of microglia and phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) following intracisternal administration of SB203580, a p38 MAPK inhibitor, or minocycline, a microglia inhibitor, in rats with temporomandibular joint (TMJ) inflammation. METHODS: The number of nociceptive behavioral responses was recorded for nine successive 5-minute intervals following formalin injections into the left TMJ. SB203580 or minocycline was administered intracisternally 2 hours prior to the formalin injection. Statistical analysis used one-way analysis of variance followed by least significant difference post-hoc analysis. RESULTS: The intra-articular injection of formalin increased the expression of p-p38 MAPK in the ipsilateral medullary dorsal horn. Most of the p-p38 MAPK co-localized with OX42, a microglial marker, but not with GFAP, an astrocyte marker. Intracisternal injections of SB203580 (0.5, 1, or 5 Μg) attenuated the number of nociceptive behavioral responses and the expression of p-p38 MAPK in the medullary dorsal horn. Intracisternal injections of minocycline (25 or 50 Μg) also attenuated the responses and the expression of OX42 and p-p38 MAPK in the medullary dorsal horn. CONCLUSION: These findings suggest that p38 MAPK in microglia plays an important role in the central processing of inflammatory TMJ nociception in rats. The data further indicate that a targeted blockade of the microglial p38 MAPK pathway is a potentially important new treatment strategy for inflammatory TMJ nociception.

Electromyographic evaluation of the 'vertical' dimension: the Learreta TMJ decompression test.

The clinical observation of the incisors overbite is the most common form used to evaluate the occlusal vertical dimension (OVD); however, this technique offers poor information about the compression state of the TMJ. In order to obtain such information, it is necessary to evaluate the electrical activity of the elevator muscles using surface electromyography (EMG). In case of a compressive irritation of the joint receptors, the trigeminal nucleus returns an inhibitory motor response of the elevator muscles that can be measured. The Learreta's EMG decompression test is done by measuring the EMG response of the masticatory muscles at maximal occlusion in four different OVD positions in such a way that the reduction of the TMJ pressure, and subsequently, relief of the inhibitory motor response can be studied. The aim of this study is to illustrate this technique, its clinical use and its limitations.

Anatomical study of the human discomallear ligament using cone beam computed tomography imaging and morphological observations.

In the present study, the human discomallear ligament (DML) was observed in structures at both macroscopic and cone beam computed tomography levels. Assessments were made regarding the distribution of calcitonin-gene-related peptide (CGRP), protein gene-product (PGP) 9.5, and substance P (SP) of the DML based on immunohistochemical analyses of the anatomical properties of jaw movements using 27 Japanese human cadavers (mean, 79.3 +/- 8.6 years; male, 74.9 +/- 8.0; female, 82.8 +/- 7.5). The DML of the anterior region was connected to the TMJ disc. The DML of the posterior region was attached to both the head and the anterior process of the malleus through the petrotympanic fissure, which formed a narrow channel. The structure of the petrotympanic fissure through the DML was attached to the malleus, and this structure was associated with the mobility of the malleus. In the anterior and posterior parts of the disc-associated connective tissue of the DML, CGRP-, PGP9.5- and SP-positive nerve fibers were located around numerous blood vessels, a condition which may be correlated with chronic pain syndrines disorders and the auditory system.

Histological and functional changes in retrodiscal tissue following anterior articular disc displacement in the rabbit: review of the literature.

AIM: Numerous studies have shown how the disc displacement, which usually occurs in an antero-medial direction, can be a factor contributing to temporomandibular joint (TMJ) pain and dysfunction. The aim of this study was to ascertain, through a critical review of the literature, current knowledge relating to anterior articular disc (ADD) in the rabbit that constitutes an extremely suitable animal model for studying the human TMJ. METHODS: An electronic search of the MEDLINE database was performed without applying time or language restrictions and using the following key words: TMD, anterior disc displacement, rabbit, bilaminar zone. This was followed by a manual search. The articles identified were assessed to verify their pertinence, or otherwise, to the topic of investigation. RESULTS: The articles examined were divided into the following groups according to the topic (histological and/or functional) they dealt with: experimental animal models, joint changes, elastic fibers, collagen, chondrocytes and nervous tissue. CONCLUSION: The papers reviewed covered many aspects, both microscopic and histochemical, of the dysfunctional picture o anterior ADD, furnishing a vast body of useful information, not only from the point of view of the results recorded, but also as regards the various surgical and analytical methods used.

Chronic orofacial pain.

Chronic orofacial pain (COFP) is an umbrella term used to describe painful regional syndromes with a chronic, unremitting pattern. This is a convenience term, similar to chronic daily headaches, but is of clinically questionable significance: syndromes that make up COFP require individually tailored diagnostic approaches and treatment. Herein we describe the three main categories of COFP: musculoskeletal, neurovascular, and neuropathic. For many years, COFP and headache have been looked upon as discrete entities. However, we propose the concept that because COFP and headaches share underlying pathophysiological mechanisms, clinical characteristics, and neurovascular anatomy, they should be classified together.

Trigeminal impingement syndrome: the relationship between atypical trigeminal symptoms and anteromedial disk displacement.

The purpose of this study was to determine if compression of the mandibular nerve and its branches could be caused by antero-medial disk displacement, resulting in atypical facial pain. Sixteen temporomandibular joints (TMJ) were dissected and injected with an autopolymerizing solution into the superior compartment, which produced an artificial capsular swelling that caused disk displacement. In all specimens, the TMJ capsule was close to the mandibular branch of the trigeminal nerve after the intracapsular injection. Thus, capsular distension or antero-medial disk displacement, as seen in various temporomandibular disorders (TMD), could result in nerve compression and facial pain symptoms.

Response properties of trigeminal ganglion mechanosensitive neurons innervating the temporomandibular joint of the rabbit.

The primary mechanosensitive neurons innervating the temporomandibular joint (TMJ neurons) may play an important role in controlling mandibular movement and position. The purpose of the study was to investigate the neurophysiological properties of TMJ neurons during passive movement of the isolated condyle in 55 rabbits and the intact condyle in 29 rabbits. Discharges of TMJ neurons from the trigeminal ganglion were recorded with a microelectrode as the isolated condyle was moved manually and by a computer-regulated mechanostimulator and as the intact condyle was manually stimulated. A total of 237 TMJ neurons were recorded rostrocaudally from the mandibular nerve area lateral to the maxillary region in the dorsal half of the trigeminal ganglion. Of the recorded TMJ units, 97% were slowly adapting (SA) and 67% of the SA units had an accompanying ongoing discharge. The proportion of adaptation types and appearance of ongoing discharges for the isolated condyle did not differ significantly from those for the intact condyle. Most of the TMJ units (89%) responded multidirectionally to the rostral and ventral movements of the isolated condyle. The discharge frequencies of the TMJ units increased as the condylar displacement and velocity increased within a 5-mm anterior displacement of the isolated condyle. Displacement of the isolated condyle influenced the discharge frequency of the units to a greater extent than the velocity of the condyle movement. No responses of TMJ units were observed during the descending ramp. Based on these results, we conclude that sensory information is transmitted by TMJ neurons encoding joint position, displacement and velocity in a physiological range of mandibular displacement.

Functional changes of temporomandibular joint mechanoreceptors induced by reduced masseter muscle activity in growing rats.

OBJECTIVE: To determine the influence of masseter muscle activity during growth on the functional characteristics of temporomandibular joint (TMJ) mechanoreceptors. MATERIALS AND METHODS: Sixty-six 3-week-old male Wistar rats were divided into an experimental group, in which the masseter muscles were bilaterally resected at 3 weeks of age, and a control group. Single-unit activities of the TMJ mechanoreceptors were evoked by indirect stimulation of passive jaw movement. Electrophysiologic recordings of TMJ units were made at 5, 7, and 9 weeks of age. RESULTS: During this period, the firing threshold of the TMJ units was significantly lower and the maximum instantaneous frequency of the TMJ units was significantly higher in the experimental group than in the control group. CONCLUSION: Reduced masseter activity during the growth period alters the response properties of TMJ mechanoreceptors.

Morphine modulation of temporomandibular joint-responsive units in superficial laminae at the spinomedullary junction in female rats depends on estrogen status.

The influence of analgesic agents on neurons activated by stimulation of the temporomandibular joint (TMJ) region is not well defined. The spinomedullary junction [trigeminal subnucleus caudalis (Vc)/C(1-2)] is a major site of termination for TMJ sensory afferents. To determine whether estrogen status influences opioid-induced modulation of TMJ units, the classical opioid analgesic, morphine, was given to ovariectomized (OvX) rats and OvX rats treated for 2 days with low-dose (LE2) or high-dose (HE2) 17beta-estradiol-3-benzoate. Under thiopental anesthesia, TMJ units in superficial and deep laminae at the Vc/C(1-2) junction were activated by injection of ATP (1 mm) directly into the joint space. In superficial laminae, morphine inhibited evoked activity in units from OvX and LE2 rats in a dose-related and naloxone-reversible manner, whereas units from HE2 rats were not inhibited. By contrast, in deep laminae, morphine reduced TMJ-evoked unit activity similarly in all groups. Morphine reduced the background activity of units in superficial and deep laminae and resting arterial pressure similarly in all groups. Morphine applied to the dorsal surface of the Vc/C(1-2) junction inhibited all units independently of E2 treatment. Quantitative polymerase chain reaction and immunoblots revealed a similar level of expression for mu-opioid receptors at the Vc/C(1-2) junction in LE2 and HE2 rats. These results indicated that estrogen status differentially affected morphine modulation of TMJ unit activity in superficial, but not deep, laminae at the Vc/C(1-2) junction in female rats. The site(s) for estrogen influence on morphine-induced modulation of TMJ unit activity was probably outside the medullary dorsal horn.

Estradiol replacement modifies c-fos expression at the spinomedullary junction evoked by temporomandibular joint stimulation in ovariectomized female rats.

The influence of estradiol (E2) treatment on temporomandibular joint (TMJ) nociceptive processing in the caudal trigeminal sensory brain stem complex was assessed in ovariectomized female rats by quantitative Fos-immunoreactivity (Fos-LI). After 2 days of daily injections of high (HE2) or low (LE2) dose E2 rats were anesthetized and the small fiber excitant, mustard oil (MO, 0-20%), was injected into the TMJ and after 2 h brains were processed for Fos-LI. TMJ-evoked Fos-LI in laminae I-II at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C1-2) junction and the dorsal paratrigeminal region (dPa5) was significantly greater in HE2 than LE2 rats, while Fos-LI produced at the ventral trigeminal interpolaris/caudalis transition region (Vi/Vc(vl)) was similar. E2 treatment also modified the influence of N-methyl-D-aspartate (NMDA) and AMPA receptor antagonists on TMJ-evoked Fos-LI. The NMDA antagonist, MK-801, dose-dependently reduced the Fos-LI response at the Vc/C1-2 junction in HE2 rats, while only high dose MK-801 was effective in LE2 rats. MK801 reduced equally the Fos-LI response at the Vi/Vc transition in both groups, while only minor effects were seen at the dPa5 region. The AMPA receptor antagonist, NBQX, reduced Fos-LI at the Vc/C(1-2) and Vi/Vc(vl) regions in HE2 rats, while only high dose NBQX was effective in LE2 rats. NBQX did not reduce Fos-LI at the dPa5 region in either group. These results suggest that estrogen status plays a significant role in TMJ nociceptive processing at the Vc/C1-2 junction mediated, in part, through ionotropic glutamate receptor-dependent mechanisms.

Macroscopic and microscopic aspects of the temporomandibular joint related to its clinical implication.

In order to obtain a precise diagnosis and treatment for temporomandibular dysfunctions, it is necessary to have morphological and functional knowledge of the temporomandibular joint. Anatomic components are important to the understanding of the complexity of temporomandibular joint. Nonetheless, just as important are the anatomic relationships that this joint has with the neighboring structures. Thus, the aim of this study was to present the anatomic relationships of the temporomandibular joint in its various surfaces: external or lateral, anterior, posterior, medial, superior, and posterosuperior, considering the morphological and histological aspects. Nine human heads, fixed in formalin (10%) underwent sagittal medial section and were subsequently dissected, evidencing the anatomic components of all surfaces to be analyzed. Components of the external surface were: skin, subcutaneous tissue, lymphatic ganglia, parotid gland, superficial temporal artery, transverse facial artery, zygomatic-orbital artery, superficial temporal vein, facial and auriculotemporal nerves, masseter muscle, and pre-auricular lymphonodus. The anterior surface comprised the masseter and lateral pterygoid muscles (upper and inferior heads), pterygoid venous plexus, mandibular notch, posterior deep temporal artery, masseteric nerve, and deep posterior temporal branches. Medial surface components were: internal maxillary artery, of which middle meningeal artery was one of the closest branches to the TMJ, anterior tympanic artery, inferior alveolar, lingual, auriculotemporal, and chorda tympani nerves, which belonged to the surface posterior to the anterior wall of the auditory duct; auricolotemporal nerve, parotid gland; and petrotympanic fissure. The cerebral fossa (meninges and encephalon) belonged to the superior surface and the ear belonged to the posterosuperior surface. Histologically, the temporomandibular joint is composed by different tissues that compound the mandibular head, mandibular fossa, and articular eminence of the temporomandibular joint. It was concluded that the temporomandibular joint is a complex structure and the clinician must have the ability to formulate the diagnosis based on the understanding of morphological aspects of the structures that compose the stomatognatic system.