Novel Apocynin regulates TRPV1 activity in the trigeminal system and controls pain in a temporomandibular joint neurogenic model.

OBJECTIVE: Herein, we investigate the potential analgesic effect of a newly synthesized chalcone-derived apocynin in a neurogenic pain model. METHODS: Molecular docking was used to foretell the apocynin binding features and dynamics with the TRPV1 channel, and the activity was tested in vitro, using transfected HEK 293T cells with the rat TRPV1 receptor. The analgesic effect of apocynin was investigated using a capsaicin-induced pain model. The expression of TRPV1, TRPA1, TRPM8, and MAPKs was assessed by electrophoresis, and immunosorbent assays were performed to quantify the neurotransmitters Substance P, Glutamate, and CGRP. A survival assay using Galleria mellonella was carried out to determine the toxicity. RESULTS: We observed that apocynin exhibits greater thermodynamic stability. Upon apocynin ligand binding, it changes the electrostatic potential for a predominantly electronegative state in the interior and neutral in its external vanilloid pocket. Treatment of apocynin induces antinociceptive effects against the noxious challenge of capsaicin. Histologically, apocynin decreased the number of TRPV1+ immunopositive cells. Electrophoresis showed reduced phosphorylation of p44/42 (ERK1/2) and decreased protein levels of substance P, and CGRP. In the survival assay, apocynin showed low toxicity. CONCLUSIONS: In conclusion, we provide proof-of-principles that the newly synthesized apocynin compound effectively prevented nociception in a neurogenic model of orofacial pain.

Enhancing orofacial pain relief: α-phellandrene complexed with hydroxypropyl-ß-cyclodextrin mitigates orofacial nociception in rodents.

Orofacial pain affects 10-15% of adults and can severely impact quality of life. Despite ongoing treatment challenges, monoterpene alpha-phellandrene (PHE) shows potential therapeutic benefits. This study aimed to develop and evaluate an inclusion complex of PHE with hydroxypropyl-beta-cyclodextrin (PHE-HPßCD) for treating orofacial pain. The PHE-HPßCD complex was created using physical mixing and characterized by differential scanning calorimetry (DSC) and high-performance liquid chromatography (HPLC) to determine encapsulation efficiency. The complex exhibited a 70.45% encapsulation efficiency. Male Swiss mice were used in models of orofacial pain induced by formalin, cinnamaldehyde, glutamate, and corneal nociception by hypertonic saline. Additionally, cytokine levels (TNF-α and IL-1ß) were measured in the upper lip tissue of mice subjected to the formalin model. Both PHE and PHE-HPßCD showed significant antinociceptive effects at a 50 mg/kg dose during formalin-induced pain, reducing both neurogenic and inflammatory phases of pain. PHE-HPßCD also reduced TNF-α and IL-1ß levels. For cinnamaldehyde and glutamate-induced nociception, both treatments reduced pain behavior, but only PHE-HPßCD decreased eye wipes in corneal nociception. These results suggest that PHE, especially in complexed form, alleviates orofacial pain by potentially modulating pain-related receptors (TRPA1 and TRPV1), mediators, like glutamate, and reducing pro-inflammatory cytokines. Further research is needed to explore the precise mechanisms of PHE in chronic orofacial pain models, but the study indicates promising avenues for new pain treatments.

Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.

Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels. Acute nociceptive behavior was induced by administering cinnamaldehyde or capsaicin to the upper lip. Nociceptive behavior was assessed through orofacial rubbing, and the effects of pre-treatment with metformin (125 or 250 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The chronic pain model involved infraorbital nerve transection (IONX) was evaluated using Von Frey electronic filaments. Trpv1 gene expression was analyzed in the nerve ganglion. Docking experiments were performed. Metformin, but not the vehicle, produced antinociception (p < 0.0001) in all acute nociceptive behaviors in both sexes, and these effects were attenuated by the TRPV1 antagonist capsazepine and the TRPA1 antagonist HC-030031. In IONX with better (**p < 0.01, ****p < 0.0001 vs. control) results in females. TRPV1 gene expression was observed in the metformin treated group (*p < 0.05 vs. control). Docking experiments revealed that metformin may interact with TRPV1 and TRPA1 channels. Metformin promotes orofacial antinociception in both sexes in acute pain and is more effective in chronic pain in females than in males, through the modulation of TRPV1 and TRPA1 channels. These preclinical findings suggest a potential repositioning of metformin as an analgesic agent in acute and chronic orofacial pain states.

Orofacial Migraine-A Narrative Review.

The diagnosis of migraine is based on clear criteria outlined in the International Classification of Headache Disorders version 3 (ICHD-3). Notably, the criteria in ICHD-3 omit the location of the migraine. There are increasing reports of migraine in the facial region. Facial presentations of migraine are not easy to diagnose as they appear in the lower two-thirds of the face, often in the maxillary sinus region, around the ear, the upper/lower jaws, and the teeth. Additionally, a similar but distinct entity, neurovascular orofacial pain, has been established. The symptomatology of facial presentations of these headaches often resembles sinusitis and dental pathology. We will review these presentations, their diagnosis, and possible pathophysiology.

Pediatric Dentists' Practice Patterns in the Screening, Diagnosis, and Management of Temporomandibular Disorders.

BACKGROUND/OBJECTIVES: Pain associated with temporomandibular disorders (TMDs) is the main non-odontogenic cause of orofacial pain among youth. Pediatric dentists are often the first healthcare practitioners to perform a comprehensive oral examination in children, which should include evaluation of the temporomandibular joint, masticatory muscles, and surrounding structures for signs and/or symptoms of TMD. This study assessed pediatric dentists' practice patterns in the screening, diagnosis, and management of TMD. METHODS: A 19-item online survey was used to assess pediatric dentists' clinical practice patterns and perceived knowledge and comfort levels in the screening, diagnosis, and management of TMD. The survey was distributed in July 2024, with a one-month window open for the study. Confidence levels and perceived knowledge were compared according to years from graduation and frequency of TMD screening assessment with ANOVA or independent t-test, as appropriate. Open-ended items were analyzed thematically. RESULTS: A total of 206 pediatric dentists and pediatric dentistry residents participated in this study. A share of 72.8% of respondents reported that up to 25% of their patients per week present with signs and symptoms of TMD. About one-fifth of pediatric dental providers never complete a screening history for TMD (22.1%) or a clinical assessment of TMD-related structures (21.6%). There was overall low self-perceived knowledge and confidence among pediatric dentists regarding the diagnosis, screening, and management of TMD in children and adolescents, regardless of the number of years from graduation. Respondents who reported seeing up to 50% of TMD patients reported significantly more knowledge and confidence in diagnosing pediatric TMD than those who encountered fewer TMD patients. An overwhelming majority (81.6%) indicated a need for continuing education courses and training focused on the management of TMD in pediatric patients. CONCLUSIONS: Providers reported low confidence and self-perceived knowledge about TMD in pediatric populations, a high rate of referral of patients with TMD, and a particular interest for professional development opportunities focused on management of TMD.

Obstructive sleep apnoea, sleep bruxism and gastroesophageal reflux - mutually interacting conditions? A literature review.

The purpose of the present manuscript is to provide an overview for researchers and clinicians summarizing the knowledge concerning the relationship between some of the main sleep-related conditions of dental interest: sleep bruxism (SB), obstructive sleep apnoea (OSA) and gastroesophageal reflux disease (GERD). Starting with the discussion of the evolving current knowledge on SB, the interconnections are discussed. Most of the available literature focused on the possible relationship between OSA and SB, but a clear pathophysiological connection or temporal relationship has not been identified. Despite the paucity of data on the possible commonalities, SB, OSA and GERD constitute a complex network of conditions that may affect the clinical and research dental practice, and they are rarely found in isolation. In this scenario, the key role of dental practitioners as sentinel in the case of these sleep-related conditions is important, thanks to their ability and the knowledge to identify signs, symptoms and risk factors that are signs of ongoing sleep-related conditions. Thus, dental practitioners are recommended to view bruxism as a potential gateway to medicine.

Cleft lip and palate and periconception COVID-19 infection in five arab countries.

BACKGROUND: Little is known about factors associated with the severity of cleft lip with or without cleft palate (CL/P) especially during the COVID-19 pandemic with its dramatic changes. OBJECTIVES: The aim of this multi-national study is to measure the association between CL/P severity, COVID-19 infection, and fear of COVID-19 in five Arab countries. METHODS: This cross-sectional study took place in major governmental hospitals in five Arab countries from November 2020 to April 2023. Participants were infants born with CL/P and their mothers who were in their 1st trimester during the COVID-19 pandemic. Clinical examination was carried out, and CL/P cases were grouped according to phenotype: cleft lip and palate (CLP) versus cleft lip (CL), cleft extension (incomplete versus complete), and site (unilateral versus bilateral) to assess severity. Information on maternal COVID-19 infection and fear of COVID-19 were gathered. RESULTS: The study recruited 273 CL/P infants. Maternal COVID-19 infection during one-month pre-gestation and 1st trimester was significantly associated with higher odds of CL/P severity (AOR = 2.707; P = 0.002) than mothers without the COVID-19 infection. Using supplements during pregnancy showed a protective effect (AOR = 0.573; P = 0.065). CONCLUSION: Mothers infected with COVID-19 before and during pregnancy had more than twofold higher odds of having an infant with a more severe CL/P phenotype.

Cervical Spinal Cord Stimulation for Treatment of Sympathetically Mediated Orofacial Pain: Case Series and Narrative Review.

OBJECTIVES: Sympathetically mediated orofacial pain is a rare form of craniofacial pain that may be refractory to conventional medical management. We report two cases of orofacial pain with sympathetic features treated with cervical spinal cord stimulation (SCS) using burst waveform with passive recharge. In addition, we present a narrative review of cervical SCS use in the management of orofacial pain. MATERIALS AND METHODS: The MEDLINE (PubMed) data base was queried for studies of orofacial pain and cervical SCS by searching applicable keywords including "face," "facial pain," "trigeminal neuralgia," "complex regional pain syndrome," and "spinal cord stimulation." Studies in the English language published between January 1, 2010 and December 31, 2023 were reviewed for relevance. RESULTS: Our literature review identified eight studies of cervical SCS use for treating orofacial pain. Our case series and literature review indicate that cervical SCS is probably safe and promising in the treatment of orofacial pain unresponsive to conventional management. Prior studies report positive results in patients with trigeminal nerve-related pain but are retrospective, include a small sample size, and are heterogenous regarding the follow-up period. We report significant analgesia in two patients with sympathetically mediated orofacial pain treated with cervical SCS using burst waveform with passive recharge. CONCLUSIONS: Cervical SCS is a viable therapeutic option for patients with orofacial pain syndromes including those with sympathetic features, although further randomized clinical studies are warranted that should include a comprehensive set of outcomes measuring pain intensity, physical function, emotional function, quality of life, and general well-being.

The Influence of Wind Musical Instruments on the Orofacial System.

OBJECTIVES: The main objective of this study was to assess whether there are differences in the muscular and occlusal levels between wind players and the general population, in addition to assessing the different repercussions depending on the embouchure type. MATERIAL AND METHODS: Two cohorts were chosen: one of them comprised intermediate students related to the practice of a wind instrument (n = 39), and the other one, harmonized with the former, comprised secondary students that served as a control group (n = 19). Overjet, overbite, presence of lip abrasion and/or erosion, Angle's molar class, Little's irregularity index, dental abrasion, presence of labial herpes, presence of tooth sensitivity, and presence of articular noises muscle pain were evaluated. RESULTS: Significant statistical differences between the groups were found regarding overjet, overcrowding of teeth, lower lip erosion, and dental abrasion, which was higher in musicians. Lastly, within the group of musicians, it was proven that tooth sensitivity was higher in the group of brass musicians. CONCLUSIONS: Wind instrument practice may be a risk factor for developing some orofacial involvement, and there are no differences among the various existing mouthpieces.

The crucial role of NR2A mediating the activation of satellite glial cells in the trigeminal ganglion contributes to orofacial inflammatory pain during TMJ inflammation.

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear. This study utilized male and female mice to induce the TMJOA model by injecting Complete Freund's adjuvant (CFA) into the TMJ and achieve conditional knockout (CKO) of NR2A in the TG using Cre/Loxp technology. The Von-Frey filament test results showed that CFA-induced orofacial pain with reduced mechanical withdrawal threshold (MWT), which was not developed in NR2A CKO mice. Additionally, the up-regulation of interleukin (IL)-1ß, IL-6, and nerve growth factor (NGF) in the TG induced by CFA did not occur by NR2A deficiency. In vitro, NMDA activated satellite glial cells (SGCs) with high expression of glial fibrillary acidic protein (GFAP), and both NMDA and LPS led to increased IL-1ß, IL-6, and NGF in SGCs. NR2A deficiency reduced these stimulating effects of NMDA and LPS. The regulation of IL-1ß involved the p38, Protein Kinase A (PKA), and Protein Kinase C (PKC) pathways, while IL-6 signaling relied on PKA and PKC pathways. NGF regulation was primarily through the p38 pathway. This study highlighted NR2A's crucial role in the TG peripheral sensitization during TMJ inflammation by mediating ILs and NGF, suggesting potential targets for orofacial inflammatory pain management.

Tongue and Lip Strength and Endurance in Healthy Young Adults With and Without Orofacial Myofunctional Disorders.

BACKGROUND/OBJECTIVES: Based on the premise that tongue and lip force is affected in individuals with orofacial myofunctional disorders (OMDs), orofacial myofunctional therapy (OMT) programs typically include the strengthening of orofacial muscles through isometric and isotonic exercises. The purpose of this study is to examine whether there is indeed a measurable difference in maximum tongue and lip strength and endurance between subjects with and without OMDs, as well as to explore Oral Health-Related Quality of Life (OHRQoL) in this population. METHODS: Sixty healthy young adults (mean age 18.9 years, SD 0.69 years, range 18.0-21.4 years) participated in this study. Perceptual evaluation of orofacial functions was conducted using the Orofacial Myofunctional Evaluation with Scores (OMES) protocol. Participants were divided into three groups, namely those with physiological orofacial functions (POF; n = 20), those with inconsistent orofacial functions (IOF; n = 11), and those with consistent OMDs (OMD; n = 29). Maximum isometric pressure and endurance of tongue and lips were measured using the Iowa Oral Performance Instrument (IOPI). OHRQoL was assessed using the Oral Health Impact Profile (OHIP-14). RESULTS: The OMES total scores did not differ significantly between the three groups, though the subscale 'function' showed significant differences (13.637; p = 0.001). No statistically significant differences in maximum isometric pressure or endurance for tongue and lips, nor for OHIP scores, were measured between the three groups. CONCLUSIONS: Although orofacial muscle strengthening is commonly part of OMT, current findings suggest the superfluity of these types of exercises in the treatment of OMDs in healthy young adults and may indicate the need to focus on awareness and rehabilitation of pathological functions in these individuals. Re-evaluation of the efficacy of OMT programs in different populations may be an important strategy going forward.

Tensile force impairs lip muscle regeneration under the regulation of interleukin-10.

BACKGROUND: Orbicularis oris muscle, the crucial muscle in speaking, facial expression and aesthetics, is considered the driving force for optimal lip repair. Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how different surgical manipulations affect lip muscle regeneration, limiting efforts to seek effective interventions. METHODS: In this study, we established a rat lip surgery model where the orbicularis oris muscle was injured by manipulations including dissection, transection and stretch. The effect of each technique on muscle regeneration was examined by histological analysis of myogenesis and fibrogenesis. The impact of tensile force was further investigated by the in vitro application of mechanical strain on cultured myoblasts. Transcriptome profiling of muscle satellite cells from different surgical groups was performed to figure out the key factors mediating muscle fibrosis, followed by therapeutic intervention to improve muscle regeneration after lip surgeries. RESULTS: Evaluation of lip muscle regeneration till 56 days after injury revealed that the stretch group resulted in the most severe muscle fibrosis (n = 6, fibrotic area 48.9% in the stretch group, P < 0.001, and 25.1% in the dissection group, P < 0.001). There was the lowest number of Pax7-positive nuclei at Days 3 and 7 in the stretch group (n = 6, P < 0.001, P < 0.001), indicating impaired satellite cell expansion. Myogenesis was impaired in both the transection and stretch groups, as evidenced by the delayed peak of centrally nucleated myofibers and embryonic MyHC. Meanwhile, the stretch group had the highest percentage of Pdgfra+ fibro-adipogenic progenitors infiltrated area at Days 3, 7 and 14 (n = 6, P = 0.003, P = 0.006, P = 0.037). Cultured rat lip muscle myoblasts exhibited impaired myotube formation and fusion capacity when exposed to a high magnitude (ε = 2688 µ strain) of mechanical strain (n = 3, P = 0.014, P = 0.023). RNA-seq analysis of satellite cells isolated from different surgical groups demonstrated that interleukin-10 was the key regulator in muscle fibrosis. Administration of recombinant human Wnt7a, which can inhibit the expression of interleukin-10 in cultured satellite cells (n = 3, P = 0.041), exerted an ameliorating effect on orbicularis oris muscle fibrosis after stretching injury in surgical lip repair. CONCLUSIONS: Tensile force proved to be the most detrimental manoeuvre for post-operative lip muscle regeneration, despite its critical role in correcting lip and nose deformities. Adjunctive biotherapies to regulate the interleukin-10-mediated inflammatory process could facilitate lip muscle regeneration under conditions of high surgical tensile force.

Higher Incidence of Common Polymorphisms in the Genes of Folate and Methionine Cycles in Children With Orofacial Clefs and Congenital Heart Defects Compared to their Unaffected Siblings.

BACKGROUND: Uninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one-carbon-activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus. METHODS: We used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD-affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD-affected and unaffected siblings. RESULTS: Only the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the FPGS gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate-methionine cycles. CONCLUSIONS: Both OFC and CHD formation were associated with a higher number of mutated loci in genes of folate-methionine cycles, indicating polygenic and possibly multifactorial inheritance.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a 15-Year-old male presenting with orofacial Swelling.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of non-Hodgkin lymphoma that primarily affects subcutaneous tissues. Its occurrence in the orofacial region is exceptionally uncommon, presenting diagnostic challenges due to symptom overlap with more prevalent orofacial condition. CASE PRESENTATION: This report details the case of a 15-year-old male who presented with persistent left-sided facial swelling, initially misdiagnosed as facial cellulitis. Diagnostic complexity arose from the similarity of symptoms to common orofacial diseases. Comprehensive diagnostic approaches, including liquid-based thin-layer cytometry, immunohistochemistry, and advanced imaging, were pivotal in identifying SPTCL. The recurrence of symptoms following the cessation of dexamethasone treatment indicated hormone dependency. Surgical intervention and subsequent histopathological analysis confirmed SPTCL, with immunohistochemical profiling playing a critical role in the definitive diagnosis. The patient's management involved a multidisciplinary approach, leading to a referral to a hematology specialist and subsequent favorable outcomes. CONCLUSIONS: This case underscores the diagnostic challenges of orofacial lymphomas such as SPTCL and highlights the necessity for early, accurate pathological diagnosis. It emphasizes the role of advanced diagnostic techniques and the importance of a comprehensive, multidisciplinary approach in the management of such rare cases. This report contributes to the limited but growing body of literature on SPTCL in the orofacial region, providing insights for clinicians in similar future cases.

Induction of orofacial pain potentiates fibromyalgia symptoms in mice: Relevance of nociceptin system.

AIMS: Fibromyalgia patients might experience temporomandibular disorder (TMD) as a comorbidity. However, the connection between these two syndromes is not fully understood. Nociceptin (N/OFQ) and NOP receptors are implicated in both conditions, but their relevance in the comorbidity needs investigation. This study featured a comorbidity model of fibromyalgia plus TMD in mice, attempting to evaluate the significance of the N/OFQ-NOP receptor in this paradigm. MATERIALS AND METHODS: Female CF-1 mice were submitted to the fibromyalgia model induced by three daily consecutive injections of reserpine (0.25 mg/kg) and received an intra-masseter injection of complete Freund's adjuvant (CFA; 10 µl; diluted 1:1) on day four. KEY FINDINGS: There was a rise in nocifensive and depression-like behaviors in the comorbidity group, as evaluated by the Grimace scores and the tail suspension test (TST). This group displayed anxiogenic-like effects in the hole board and the elevated plus maze tests. The comorbidity group showed an increment of c-Fos immunopositivity in the ipsilateral side of CFA injection, in the trigeminal ganglion (TG) and thalamus. The administration of N/OFQ (1 nmol/kg, i.p.) boosted the Grimace scores in the comorbidity group, with no effect for the NOP receptor antagonist UFP-101 (1 nmol/kg, i.p.). Either NOP ligand failed to alter depression or anxiety behavioral changes. Alternatively, pregabalin (30 mg/kg; i.p.) reduced the nociceptive responses and the number of head dips in the hole board. SIGNIFICANCE: Data reveal new evidence suggesting that inducing TMD with CFA may worsen fibromyalgia symptoms in reserpine-treated mice, an effect partially regulated by systemic N/OFQ.

Influence of instructions and expectations in pain perception on pupil diameter and the cognitive assessment of pain.

OBJECTIVE: The purpose of this study was to analyze the influence of pain and no pain expectation on pupil diameter and the cognitive assessment of pain using pupillometry and the visual analog scale (VAS). METHODS: This was an experimental cross-sectional study in which painful stimulation of the muscle masseter was produced by palpation with an algometer in a sample of 30 healthy participants. Before the painful stimulation, pain expectation and no pain expectation situations were induced by employing instructional videos. Cognitive and physiological pain responses were measured by the VAS and by pupillometry. Visual analog scale score was assessed at the end of each experimental condition, and pupillometry measurements were recorded at different moments of the experimental process (events). RESULTS: The pain score and larger pupil diameter for all events (except, as expected, for the initial baseline), were statistically significant for the pain expectation condition compared with the no pain expectation. CONCLUSION: Within the conditions of this study, pain expectation modulated both cognitive assessment of pain (VAS) and pupil diameter. These findings suggest that pupil diameter may be a useful and complementary tool with the VAS for pain assessment. Furthermore, the findings support models postulating that emotion and cognition are important aspects involved in pain perception, which is in line with the recent International Association for the Study of Pain definition of pain.

The Trigeminal Sensory System and Orofacial Pain.

The trigeminal sensory system consists of the trigeminal nerve, the trigeminal ganglion, and the trigeminal sensory nuclei (the mesencephalic nucleus, the principal nucleus, the spinal trigeminal nucleus, and several smaller nuclei). Various sensory signals carried by the trigeminal nerve from the orofacial area travel into the trigeminal sensory system, where they are processed into integrated sensory information that is relayed to higher sensory brain areas. Thus, knowledge of the trigeminal sensory system is essential for comprehending orofacial pain. This review elucidates the individual nuclei that comprise the trigeminal sensory system and their synaptic transmission. Additionally, it discusses four types of orofacial pain and their relationship to the system. Consequently, this review aims to enhance the understanding of the mechanisms underlying orofacial pain.

Temporomandibular disorders: INfORM/IADR key points for good clinical practice based on standard of care.

OBJECTIVE: To present a list of key points for good Temporomandibular Disorders (TMDs) clinical practice on behalf of the International Network for Orofacial Pain and Related Disorders Methodology (INfORM) group of the International Association for Dental, Oral and Craniofacial Research (IADR). METHODS: An open working group discussion was held at the IADR General Session in New Orleans (March 2024), where members of the INfORM group finalized the proposal of a list of 10 key points. RESULTS: The key points covered knowledge on the etiology, diagnosis, and treatment. They represent a summary of the current standard of care for management of TMD patients. They are in line with the current need to assist general dental practitioners advance their understanding and prevent inappropriate treatment. CONCLUSIONS: The key points can be viewed as a guiding template for other national and international associations to prepare guidelines and recommendations on management of TMDs adapted to the different cultural, social, educational, and healthcare requirements.

The neural substrates of bruxism: current knowledge and clinical implications.

Bruxism is a complex orofacial behavior that can occur during sleep or wakefulness, characterized by the involuntary grinding or clenching of teeth, involving repetitive activity of the jaw muscles. Its etiology is multifactorial, influenced by genetic, psychological, physiological, and lifestyle factors. While the mild bruxism may not necessitate treatment, severe bruxism can lead to significant consequences, including tooth damage, jaw pain, fatigue, and headaches. The bruxism has been associated with medical conditions, such as stress, anxiety, sleep disorders, and various neurological disorders; however, the exact pathophysiology remains elusive. Although the central nervous system is strongly implicated in the development of bruxism, specific neural substrates have not yet been conclusively established. Furthermore, there is evidence to suggest that individuals with bruxism may exhibit neural plasticity, resulting in the establishment of distinct neural circuitry that control the jaw movements. The application of various neurophysiological techniques in both clinical and pre-clinical studies provides valuable insights into the neural mechanisms underlying bruxism. This review aims to comprehensively examine the current literature on the neural pathways involved in bruxism, with the goal of improving the clinical approach and therapeutics for this condition. A deeper understanding of the neural circuitry controlling bruxism holds the potential to advance future treatment approaches and improve the management of patients with bruxism.

Phenotyping of somatosensory tinnitus and its associations: An observational cross-sectional study.

BACKGROUND: Somatosensory tinnitus (ST) is associated with activation of the auditory pathway by trigeminal or cervical afferents. OBJECTIVE: This is a cross-sectional observational study that aims to verify the association of ST with TMD, bruxism, migraine and psychosocial aspects. METHODS: This study was conducted at the Tinnitus Outpatient Clinic of the Clinical Hospital Complex of the Federal University of Paraná. Specific ST characteristics, were evaluated according to the last consensus for the diagnosis of ST. Two groups with 39 individuals each one were formed, the ST group (STG) and the comparison group (CG). TMD was classified according to the Diagnostic Criteria for Temporomandibular Disorders and migraine by the International Classification of Headaches. The presence of probable sleep and awake bruxism was associated with individual's reports and clinical inspections. The applied questionnaires investigated oral behaviours (OB), sleep quality (SQ), psychosocial aspects (PA), central sensitization (CS), tinnitus impact on quality of life (TIQF), and graded chronic pain scale (GCPS). RESULTS: The STG showed a significant association with modulation manoeuvres and trigger points; myalgias and arthralgia; disc displacement with and without reduction; subluxation; bruxism; and presence of migraine. For the same group, we found a significant association with OB, PA, CS, TIQF and GCPS. There was no significant difference between groups regarding SQ. CONCLUSION: There is a significant association between the presence of ST and the occurrence of TMD, probable sleep and awake bruxism, and migraine. There is also a greater impairment of OB, PA, CS and TIQF.