The purinergic receptor P2X3 promotes facial pain by activating neurons and cytokines in the trigeminal ganglion.

The mechanism underlying allodynia/hyperalgesia caused by dental pulpitis has remained enigmatic. This investigation endeavored to characterize the influence of the purinergic receptor P2X3 on pain caused by experimental pulpitis and the mechanism involved. An experimental model of irreversible pulpitis was produced by the drilling and exposure of the dental pulp of the left upper first and second molars in rats, followed by measuring nociceptive responses in the oral and maxillofacial regions. Subsequently, neuronal activity and the expression of P2X3 and pertinent cytokines in the trigeminal ganglion (TG) were meticulously examined and analyzed. Histological evidence corroborated that significant pulpitis was produced in this model, which led to a distinct escalation in nociceptive responses in rats. The activation of neurons, coupled with the upregulated expression of c-fos, P2X3, p-p38, TNF-α and IL-1ß, was identified subsequent to the pulpitis surgery within the TG. The selective inhibition of P2X3 with A-317491 effectively restrained the abnormal allodynia/hyperalgesia following the pulpitis surgery and concurrently inhibited the upregulation of p-p38, TNF-α and IL-1ß within the TG. These findings suggest that the P2X3 signaling pathway plays a pivotal role in instigating and perpetuating pain subsequent to the induction of pulpitis in rats, implicating its association with the p38 MAPK signaling pathway and inflammatory factors.

Involvement of oxidative stress in orofacial mechanical pain hypersensitivity following neonatal maternal separation in rats.

Patients with persistent pain have sometimes history of physical abuse or neglect during infancy. However, the pathogenic mechanisms underlying orofacial pain hypersensitivity associated with early-life stress remain unclear. The present study focused on oxidative stress and investigated its role in pain hypersensitivity in adulthood following early-life stress. To establish an early-life stress model, neonatal pups were separated with their mother in isolated cages for 2 weeks. The mechanical head-withdrawal threshold (MHWT) in the whisker pad skin of rats received maternal separation (MS) was lower than that of non-MS rats at postnatal week 7. In MS rats, the expression of 8-hydroxy-deoxyguanosine, a marker of DNA oxidative damage, was enhanced, and plasma antioxidant capacity, but not mitochondrial complex I activity, decreased compared with that in non-MS rats. Reactive oxygen species (ROS) inactivation and ROS-sensitive transient receptor potential ankyrin 1 (TRPA1) antagonism in the whisker pad skin at week 7 suppressed the decrease of MHWT. Corticosterone levels on day 14 increased in MS rats. Corticosterone receptor antagonism during MS periods suppressed the reduction in antioxidant capacity and MHWT. The findings suggest that early-life stress potentially induces orofacial mechanical pain hypersensitivity via peripheral nociceptor TRPA1 hyperactivation induced by oxidative stress in the orofacial region.

Pior qualidade de sono está associada à disfunção temporomandibular e hábitos parafuncionais entre estudantes e profissionais de Odontologia / La peor calidad del sueño se asocia con disfunción temporomandibular y hábitos parafuncionales en estudiantes y profesionales de Odontología / Worse sleep quality is associated with temporomandibular disorders and parafunctional habits among dental students and professionals

Este estudo teve como objetivo avaliar a associação entre a qualidade do sono e a presença de disfunção temporomandibular (DTM) e hábitos parafuncionais em estudantes e profissionais de Odontologia durante a pandemia de COVID-19. Cirurgiões-dentistas, docentes e estudantes brasileiros de graduação e pós-graduação em Odontologia responderam a um questionário virtual composto pelos seguintes instrumentos: Índice de Qualidade do Sono de Pittsburgh, Lista de Verificação de Comportamentos Orais, Índice Anamnésico de Fonseca e questões socioeconômicas e demográficas. Os questionários foram disponibilizados online de agosto a novembro de 2020. A associação entre as variáveis preditoras e cada desfecho foi avaliada por meio da regressão de Poisson. A amostra foi composta por 449 participantes, sendo que 259 (59,5%) relataramdistúrbios do sono, 352 (78,4%) apresentavam DTM e 311 (69,3%) realizavam hábitos orais parafuncionais. Os distúrbios do sono foram associados à maior prevalência de hábitos orais parafuncionais (RP 1,61; IC 95% 1,36-1,91) e DTM (RP 1,16; IC 95% 1,04-1,29). Além disso, as mulheres apresentaram maior prevalência de DTM em relação aos homens, assim como indivíduos cuja renda era menor. Desta forma, os distúrbios do sono foram associados a hábitos orais parafuncionais e DTM em estudantes e profissionais de Odontologia durante a quarentena da COVID-19 (AU).

Este estudio tuvo como objetivo evaluar la asociación entre la calidad del sueño y la presencia de disfunción temporomandibular (DTM) y hábitos parafuncionales en estudiantes y profesionales de Odontología durante la pandemia de COVID-19. Odontólogos, profesores y estudiantes brasileños de pregrado y posgrado en Odontología respondieron un cuestionario virtual compuesto por los siguientes instrumentos: Índice de Calidad de Sueño de Pittsburgh, Lista de Verificación de Comportamiento Oral, Índice Anamnésico de Fonseca y preguntas socioeconómicas y demográficas. Los cuestionarios estuvieron disponibles virtualmente de agosto a noviembre de 2020. La asociación entre las variables predictoras y cada resultado se evaluó mediante regresión de Poisson. La muestra estuvo compuesta por 449 participantes, de los cuales 259 (59,5%) refirieron trastornos del sueño, 352 (78,4%) DTM y 311 (69,3%) hábitos orales parafuncionales. Los trastornos del sueño se asociaron con una mayor prevalencia de hábitos bucales parafuncionales (RP 1,61; IC 95% 1,36-1,91) y DTM (RP 1,16; IC 95% 1,04-1,29). Además, las mujeres tenían una mayor prevalencia de DTM que los hombres, así como las personas con ingresos más bajos. Así, los trastornos del sueño se asociaron con hábitos orales parafuncionales y DTM en estudiantes y profesionales de odontología durante la cuarentena por COVID-19 (AU).

This study aimed to assess the association between sleep quality and the presence of temporomandibular disorders (TMD) and parafunctional habits in dental students and professionals during the COVID-19 quarantine. Brazilian dentists, professors, and dental undergraduate and graduate students answered a virtual questionnaire composed of the following instruments: Pittsburgh Sleep Quality Index. Oral Behaviors Checklist, Fonseca Anamnestic Index, and socioeconomic and demographic questions. Questionnaires were available on-line from August to November 2020. The association between the predictor variables and each outcome were assessed using Poisson regression. The sample consisted of 449 participants, 259 (59.5%) of whom had sleep disorders, 352 (78.4%) had TMD, and 311 (69.3%) had parafunctional oral habits. Sleep disorders were associated with higher prevalence of parafunctional oral habits (PR 1.61; 95%CI 1.36-1.91) and TMD (PR 1.16; 95%CI 1.04-1.29). Furthermore, women showed a higher prevalence of TMD in comparison to men, as well as individuals with lower income. Sleep disorders were associated with parafunctional oral habits and TMD in dental students and professionals during COVID-19 quarantine (AU).

Neonatal Injury Modulates Incisional Pain Sensitivity in Adulthood: An Animal Study.

Neonatal pain experiences including traumatic injury influence negatively on development of nociceptive circuits, resulting in persistent pain hypersensitivity in adults. However, the detailed mechanism is not yet well understood. In the present study, to clarify the pathogenesis of orofacial pain hypersensitivity associated with neonatal injury, the involvement of the voltage-gated sodium channel (Nav) 1.8 and the C-C chemokine ligand 2 (CCL2)/C-C chemokine receptor 2 (CCR2) signaling in the trigeminal ganglion (TG) in facial skin incisional pain hypersensitivity was examined in 190 neonatal facial-injured and sham male rats. The whisker pad skin was incised on postnatal day 4 and week 7 (Incision-Incision group). Compared to the group without neonatal incision (Sham-Incision group), mechanical hypersensitivity in the whisker pad skin was enhanced in Incision-Incision group. The number of Nav1.8-immunoreactive TG neurons and the amount of CCL2 expressed in the macrophages and satellite glial cells in the TG were increased on day 14 after re-incision in the Incision-Incision group, compared with Sham-Incision group. Blockages of Nav1.8 in the incised region and CCR2 in the TG suppressed the enhancement of mechanical hypersensitivity in the Incision-Incision group. Administration of CCL2 into the TG enhanced mechanical hypersensitivity in the Sham-Sham, Incision-Sham and Sham-Incision group. Our results suggest that neonatal facial injury accelerates the TG neuronal hyperexcitability following orofacial skin injury in adult in association with Nav1.8 overexpression via CCL2 signaling, resulting in the enhancement of orofacial incisional pain hypersensitivity in the adulthood.

Primary neurolymphomatosis of the trigeminal nerve.

We report a case of a primary malignant lymphoma of the trigeminal nerve that was associated with facial pain. A 65-year-old man was examined at another hospital for unilateral facial pain. Carbamazepine was prescribed, but his symptoms did not improve. Magnetic resonance imaging (MRI) revealed swelling of the trigeminal nerve and a mass lesion in Meckel's cave. The patient was referred to our hospital at this point. Gadolinium-enhanced MRI and F18-Fluorodeoxyglucose-position emission tomography suggested a likely malignant tumour and a biopsy was performed. Histopathological examination showed diffuse a large B cell lymphoma. The patient was treated with high-dose methotrexate (HD-MTX) and radiotherapy. Despite responding well to initial treatment, the patient relapsed, with lymphoma observed throughout the body. He died of pneumonia 18 months after the initial diagnosis. Facial pain is a symptom that is commonly managed in general practice. If symptoms do not improve, repeated imaging studies, including contrast MRI, is warranted. This is the first reported case of primary neurolymphomatosis (NL) of the trigeminal nerve associated with facial pain alone. Furthermore, HD-MTX and radiotherapy may be considered for the management of primary NL of a cranial nerve.

Differential roles of NMDAR subunits 2A and 2B in mediating peripheral and central sensitization contributing to orofacial neuropathic pain.

The spinal N-methyl-d-aspartate receptor (NMDAR), particularly their subtypes NR2A and NR2B, plays pivotal roles in neuropathic and inflammatory pain. However, the roles of NR2A and NR2B in orofacial pain and the exact molecular and cellular mechanisms mediating nervous system sensitization are still poorly understood. Here, we exhaustively assessed the regulatory effect of NMDAR in mediating peripheral and central sensitization in orofacial neuropathic pain. Von-Frey filament tests showed that the inferior alveolar nerve transection (IANX) induced ectopic allodynia behavior in the whisker pad of mice. Interestingly, mechanical allodynia was reversed in mice lacking NR2A and NR2B. IANX also promoted the production of peripheral sensitization-related molecules, such as interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, brain-derived neurotrophic factor (BDNF), and chemokine upregulation (CC motif) ligand 2 (CCL2), and decreased the inward potassium channel (Kir) 4.1 on glial cells in the trigeminal ganglion, but NR2A conditional knockout (CKO) mice prevented these alterations. In contrast, NR2B CKO only blocked the changes of Kir4.1, IL-1ß, and TNF-α and further promoted the production of CCL2. Central sensitization-related c-fos, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) were promoted and Kir4.1 was reduced in the spinal trigeminal caudate nucleus by IANX. Differential actions of NR2A and NR2B in mediating central sensitization were also observed. Silencing of NR2B was effective in reducing c-fos, GFAP, and Iba-1 but did not affect Kir4.1. In contrast, NR2A CKO only altered Iba-1 and Kir4.1 and further increased c-fos and GFAP. Gain-of-function and loss-of-function approaches provided insight into the differential roles of NR2A and NR2B in mediating peripheral and central nociceptive sensitization induced by IANX, which may be a fundamental basis for advancing knowledge of the neural mechanisms' reaction to nerve injury.

The Molecular Basis and Pathophysiology of Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.

Effects of buprenorphine on model development in an adjuvant-induced monoarthritis rat model.

Complete Freund's adjuvant (CFA)-induced arthritis in rats is a common animal model for studying chronic inflammatory pain. However, modelling of the disease is associated with unnecessary pain and impaired animal wellbeing, particularly in the immediate post-induction phase. Few attempts have been made to counteract these adverse effects with analgesics. The present study investigated the effect of buprenorphine on animal welfare, pain-related behaviour and model-specific parameters during the disease progression in a rat model of CFA-induced monoarthritis. The aim was to reduce or eliminate unnecessary pain in this model, in order to improve animal welfare and to avoid suffering, without compromising the quality of the model. Twenty-four male Sprague Dawley rats were injected with 20 µl of CFA into the left tibio-tarsal joint to induce monoarthritis. Rats were treated with either buprenorphine or carprofen for 15 days during the disease development, and were compared to a saline-treated CFA-injected group or a negative control group. Measurements of welfare, pain-related behaviour and clinical model-specific parameters were collected. The study was terminated after 3 weeks, ending with a histopathologic analysis. Regardless of treatment, CFA-injected rats displayed mechanical hyperalgesia and developed severe histopathological changes associated with arthritis. However, no severe effects on general welfare were found at any time. Buprenorphine treatment reduced facial pain expression scores, improved mobility, stance and lameness scores and it did not supress the CFA-induced ankle swelling, contrary to carprofen. Although buprenorphine failed to demonstrate a robust analgesic effect on the mechanical hyperalgesia in this study, it did not interfere with the development of the intended pathology.

Spinal CCK contributes to somatic hyperalgesia induced by orofacial inflammation combined with stress in adult female rats.

In some chronic primary pain conditions such as temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS), mild or chronic stress enhances pain. TMD and FMS often occur together, but the underlying mechanisms are unclear. The purpose of this study was to investigate the role of cholecystokinin (CCK) in the spinal cord in somatic hyperalgesia induced by orofacial inflammation combined with stress. Somatic hyperalgesia was detected by the thermal withdrawal latency and mechanical withdrawal threshold. The expression of CCK1 receptors, CCK2 receptors, ERK1/2 and p-ERK1/2 in the spinal cord was examined by Western blot. After the stimulation of orofacial inflammation combined with 3 day forced swim, the expression of CCK2 receptors and p-ERK1/2 protein in the L4-L5 spinal dorsal horn increased significantly, while the expression of CCK1 receptors and ERK1/2 protein remained unchanged. Intrathecal injection of the CCK2 receptor antagonist YM-022 or mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 blocked somatic hyperalgesia induced by orofacial inflammation combined with stress. Intrathecal administration of the MEK inhibitor blocked somatic sensitization caused by the CCK receptor agonist CCK8. The CCK2 receptor antagonist YM-022 significantly reduced the expression of p-ERK1/2. These data indicate that upregulation of CCK2 receptors through the MAPK pathway contributes to somatic hyperalgesia in this comorbid pain model. Thus, CCK2 receptors and MAPK pathway may be potential targets for the treatment of TMD comorbid with FMS.

Modulation of excitatory synaptic transmissions by TRPV1 in the spinal trigeminal subnucleus caudalis neurons of neuropathic pain rats.

The present study examined contribution of the transient receptor potential vanilloid 1 channel (TRPV1) to the chronic orofacial pain. Bilateral partial nerve ligation (PNL) of the mental nerve, a branch of trigeminal nerve, was performed to induce neuropathic pain. The withdrawal threshold in response to mechanical stimulation of the lower lip skin was substantially reduced after the surgery in the PNL rats while it remained unchanged in the sham rats. This reduction in the PNL rats was alleviated by pregabalin injected intraperitoneally (10 mg/kg) and intracisternally (10, 30, 100 µg). Furthermore, an intracisternal injection of AMG9810, an antagonist of TRPV1, (1.5, 5.0 µg) attenuated the reduction of withdrawal threshold. Spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) were recorded from the spinal trigeminal subnucleus caudalis (Vc) neurons in the brainstem slice, which receive the orofacial nociceptive signals. In the PNL rats, superfusion of capsaicin (0.03, 0.1 µM) enhanced their frequency without effect on the amplitude and the highest concentration (0.3 µM) increased both the frequency and amplitude. In the sham rats, only 0.3 µM capsaicin increased their frequency. Thus, capsaicin-induced facilitation of sEPSCs and mEPSCs in the PNL rats was significantly stronger than that in the sham rats. AMG9810 (0.1 µM) attenuated the capsaicin's effect. Capsaicin was ineffective on the trigeminal tract-evoked EPSCs in the PNL and sham rats. These results suggest that the chronic orofacial pain in the PNL model results from facilitation of the spontaneous excitatory synaptic transmission in the Vc region through TRPV1 at least partly.

Classification of temporomandibular joint internal derangement based on magnetic resonance imaging and clinical findings of 435 patients contributing to a nonsurgical treatment protocol.

This prospective clinical study aimed to establish a new classification system for TMJ internal derangement based on MRI in correlation with clinical findings contributing to a nonsurgical treatment protocol. A consecutive sample of 435 internal derangement patients was enrolled in the study. Clinical and MRI studies were used to establish the new classification system. A total of 747 joints were classified according to our staging system and received treatment according to the associated nonsurgical treatment protocol. The primary outcome variables were maximum voluntary mouth opening and visual analogue scale pain scores. The secondary outcome variable was joint sound. Statistical analysis of the differences between pretreatment and posttreatment measurements showed an increase in mouth opening throughout the study period (P < 0.001 at 12 m posttreatment). Statistical analysis of the VAS scores showed a statistically significant decrease in all study groups during all study periods, with P < 0.0001 at 12 months posttreatment. Statistical analysis of joint sounds showed significant improvement during all study periods. The new classification system is a simple, & reasonable including a detailed description of all the pathologic changes of the joint. The nonsurgical treatment protocol was Simple, effective and specific depending on the pathological changes in joint.

Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models.

This review highlights potential molecular targets for treating neuropathic orofacial pain based on current findings in animal models. Preclinical research is currently elucidating the pathophysiology of the disease and identifying the molecular targets for better therapies using animal models that mimic this category of orofacial pain, especially post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN). Animal models of PTNP and PTN simulate their etiologies, that is, trauma to the trigeminal nerve branch and compression of the trigeminal root entry zone, respectively. Investigations in these animal models have suggested that biological processes, including inflammation, enhanced neuropeptide-mediated pain signal transmission, axonal ectopic discharges, and enhancement of interactions between neurons and glial cells in the trigeminal pathway, are underlying orofacial pain phenotypes. The molecules associated with biological processes, whose expressions are substantially altered following trigeminal nerve damage or compression of the trigeminal nerve root, are potentially involved in the generation and/or exacerbation of neuropathic orofacial pain and can be potential molecular targets for the discovery of better therapies. Application of therapeutic candidates, which act on the molecular targets and modulate biological processes, attenuates pain-associated behaviors in animal models. Such therapeutic candidates including calcitonin gene-related peptide receptor antagonists that have a reasonable mechanism for ameliorating neuropathic orofacial pain and meet the requirements for safe administration to humans seem worth to be evaluated in clinical trials. Such prospective translation of the efficacy of therapeutic candidates from animal models to human patients would help develop better therapies for neuropathic orofacial pain.

Clinical and Pain-Related Characteristics of Idiopathic First Bite Syndrome Induced by Taste in Japanese Patients without Diabetes: A Retrospective Study of Five Cases.

Objective: First bite syndrome (FBS) is a condition in which the first bite of each meal causes parotid pain. Etiologies of FBS include prior surgery of the upper cervical region and, rarely, head and neck tumors. Idiopathic FBS rarely presents in patients without a history of surgery or evidence of an underlying tumor. Idiopathic FBS may be categorized into two subtypes: that in patients with diabetes and that in patients without diabetes. Idiopathic FBS in patients without diabetes may be overlooked or misdiagnosed because the condition has been described only in a few case reports. We aimed to identify the clinical and pain-related characteristics of idiopathic FBS in patients without diabetes. Methods: We retrospectively analyzed the clinical data of five patients without diabetes who were diagnosed with idiopathic FBS in our department between January 2010 and December 2016. Results: Four of the five patients were female, and the overall median age was 52 years (range: 13-61). All patients immediately experienced parotid pain upon tasting food without chewing. Addition of an acidic solution to the ipsilateral posterior third of the tongue evoked parotid pain. The median degree of pain intensity and interference with eating due to pain was 9 (range: 3-10) and 9 (range: 5-10) on a numerical rating scale of 0-10, respectively. Idiopathic FBS was bilateral in two patients. Two patients had tenderness on mild pressure over the affected parotid region. Two patients presented with ipsilateral idiopathic Horner's syndrome. Conclusions: Our findings indicate that the characteristics of idiopathic FBS in patients without diabetes are largely consistent with those previously reported in postoperative FBS, supporting the notion that idiopathic FBS is a subtype of FBS. Thus, it is necessary to consider idiopathic FBS during the evaluation of facial pain triggered at the beginning of a meal.

Local anaesthesia decreases nerve growth factor induced masseter hyperalgesia.

The aim of this investigation was to evaluate the effects of local anaesthesia on nerve growth factor (NGF) induced masseter hyperalgesia. Healthy participants randomly received an injection into the right masseter muscle of either isotonic saline (IS) given as a single injection (n = 15) or an injection of NGF (n = 30) followed by a second injection of lidocaine (NGF + lidocaine; n = 15) or IS (NGF + IS; n = 15) in the same muscle 48 h later. Mechanical sensitivity scores of the right and left masseter, referred sensations and jaw pain intensity and jaw function were assessed at baseline, 48 h after the first injection, 5 min after the second injection and 72 h after the first injection. NGF caused significant jaw pain evoked by chewing at 48 and 72 h after the first injection when compared to the IS group, but without significant differences between the NGF + lidocaine and NGF + IS groups. However, the mechanical sensitivity of the right masseter 5 min after the second injection in the NGF + lidocaine group was significantly lower than the second injection in the NGF + IS and was similar to the IS group. There were no significant differences for the referred sensations. Local anaesthetics may provide relevant information regarding the contribution of peripheral mechanisms in the maintenance of persistent musculoskeletal pain.

Effects of 4-Week Diacutaneous Fibrolysis on Myalgia, Mouth Opening, and Level of Functional Severity in Women With Temporomandibular Disorders: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to assess the effects of 4-week protocol of diacutaneous fibrolysis (DF) compared with simulated DF (sham-DF) on myalgia and mouth opening. METHODS: In a sham randomized controlled trial, 34 women with temporomandibular disorders and myofascial pain were randomly divided as intervention group (IG) and sham-DF group (SG). The IG received 4 weeks of real DF, and the SG received sham. Pain was assessed through the visual analog scale and pressure pain thresholds (PPTs) on the temporomandibular joint (TMJ), and over the temporal and masseter muscles. The Mandibular Function Impairment Questionnaire was used to classify the participants regarding to the severity of the functional limitation related to TMD. RESULTS: Pain scores decreased for both groups, but the IG showed lower values at week 4, with between-group differences. Bilateral temporal PPT showed higher values at week 4, with between-group differences. The SG had lower PPTs but the IG had higher PPTs, both compared to baseline results. The time-by-group interaction and the frequency of participants above 40 mm of mouth opening showed a significant difference for the IG over time with higher results at the 4-week assessment compared to its own baseline. Both groups showed lower MFIQ scores from baseline to 4-week assessment. There was a lower frequency of a moderate level of severity for the IG. No differences were observed for TMJ or for the masseter muscles PPT. CONCLUSION: Improvements were observed for visual analog scale scores and PPTs on temporal muscles. There was a group-by-time interaction in the IG, suggesting a possible potential use of DF for mouth opening.

Comparison between Conventional Blind Injections and Ultrasound-Guided Injections of Botulinum Toxin Type A into the Masseter: A Clinical Trial.

The aim of the study was to propose a more efficient and safer botulinum toxin type A (BoNT-A) injection method for the masseter by comparing the conventional blind injection and a novel ultrasonography (US)-guided injection technique in a clinical trial. The 40 masseters from 20 healthy young Korean volunteers (10 males and 10 females with a mean age of 25.6 years) were included in this prospective clinical trial. The BoNT-A (24 U) was injected into the masseter of each volunteer using the conventional blind and US-guided injection techniques on the left and right sides, respectively, and analyzed by US and three-dimensional (3D) facial scanning. One case of PMB (paradoxical masseteric bulging) was observed on the side where a conventional blind injection was performed, which disappeared after the compensational injection. The reduction in the thickness of the masseter in the resting state differed significantly at 1 month after the injection between the conventional blind injection group and the US-guided injection group by 12.38 ± 7.59% and 17.98 ± 9.65%, respectively (t(19) = 3.059, p = 0.007). The reduction in the facial contour also differed significantly at 1 month after the injection between the conventional blind injection group and the US-guided injection group by 1.95 ± 0.74 mm and 2.22 ± 0.84 mm, respectively (t(19) = 2.908, p = 0.009). The results of the study showed that the US-guided injection method that considers the deep inferior tendon by visualizing the masseter can prevent the PMB that can occur during a blind injection, and is also more effective.

Concomitant continuous pain in patients with trigeminal neuralgia is associated with trigeminal nerve root atrophy.

INTRODUCTION: Trigeminal neuralgia is an exemplary neuropathic pain condition characterized by paroxysmal electric-shock-like pain. However, up to 50% of patients also experiences concomitant continuous pain. In this neuroimaging study, we aimed to identify the specific anatomical features of trigeminal nerve root in patients with concomitant continuous pain. METHODS: We enrolled 73 patients with a definitive diagnosis of classical and idiopathic trigeminal neuralgia and 40 healthy participants. The diagnosis of trigeminal neuralgia was independently confirmed by two clinicians. Patients were grouped as patients with purely paroxysmal pain (45 patients) and patients also with concomitant continuous pain (28 patients). All participants underwent a structured clinical examination and a 3T MRI with sequences dedicated to the anatomical study of the trigeminal nerve root, including volumetric study. Images analysis was independently performed by two investigators, blinded to any clinical data. RESULTS: In most patients with concomitant continuous pain, this type of pain, described as burning, throbbing or aching, manifested at the disease onset. Demographic and clinical variables did not differ between the two groups of patients; the frequency of neurovascular compression and nerve dislocation were similar. Conversely, trigeminal nerve root atrophy was more severe in patients with concomitant continuous pain than in those with purely paroxysmal pain (p = 0.006). CONCLUSIONS: Our clinical and neuroimaging study found that in patients with trigeminal neuralgia, concomitant continuous pain was associated with trigeminal nerve root atrophy, therefore suggesting that this type of pain is likely related to axonal loss and abnormal activity in denervated trigeminal second-order neurons.

The fifth cranial nerve in headaches.

The fifth cranial nerve is the common denominator for many headaches and facial pain pathologies currently known. Projecting from the trigeminal ganglion, in a bipolar manner, it connects to the brainstem and supplies various parts of the head and face with sensory innervation. In this review, we describe the neuroanatomical structures and pathways implicated in the sensation of the trigeminal system. Furthermore, we present the current understanding of several primary headaches, painful neuropathies and their pharmacological treatments. We hope that this overview can elucidate the complex field of headache pathologies, and their link to the trigeminal nerve, to a broader field of young scientists.

The course of pain intensity and frequency of adolescents treated because of temporomandibular disorders: A long-term follow-up.

OBJECTIVES: To evaluate the course of pain intensity and frequency related to temporomandibular disorders (TMDs) 15 years (range 5-21 years) after having received TMD treatment as adolescents due to frequent (at least once a week) TMD pain in two controlled trials. MATERIALS AND METHODS: In the first trial, subjects (n = 122) were randomly allocated to either information only, received in a control condition (Co), or information and an occlusal appliance (OA) versus relaxation therapy (RT). In the second trial, including 64 subjects, nonresponders to OA or RT were subsequently allocated to the alternate treatment (ST). All study participants having completed the trials (n = 167) were invited to a long-term follow-up evaluations, with a response rate of 69.5% (n = 116). Patient-reported outcomes of TMD-related frequency and intensity were appraised relative to baseline data and short-term outcomes as observed in the two trials by use of general linear mixed model and generalized estimation equation statistics. RESULTS: A significantly higher proportion of participants treated with OA and in the combined RT/Co condition than those in the ST group, reported a frequency level of TMD pain less than once week at post-treatment and the long-term follow-up. Adolescents treated with OA showed significantly lower TMD pain intensity levels post-treatment than those in the other two treatment conditions. While no difference between the OA and the RT/Co conditions was found in the long-term follow-up, participants in these two conditions were significantly more improved than those in the ST group. CONCLUSION: Adolescents treated with an OA clearly showed better outcome with regard to intensity and frequency in a long-term follow-up of TMD pain than those treated with RT and ST for nonresponders. These latter individuals need special clinical attention and more effective supplementary treatment methods to be developed.