Effectiveness of photobiomodulation and orofacial myofunctional therapy in orofacial pain disorders. A systematic review of randomized control trials.

Orofacial pain can significantly affect physical, psychological, and overall quality of life. This study aimed to compare the effectiveness of combining photobiomodulation (PBM) with orofacial myofunctional therapy (OMT) in managing orofacial pain disorders. An electronic search of randomized controlled trials in electronic databases was performed until March 2024. Randomized controlled trials (RCTs) focusing on PBM and OMT for the management of orofacial pain were included. Risk of bias across individual studies was performed using the Cochrane risk of bias tool for interventions. A total of 10 RCTs were included, out of which 7 RCTs revealed that the combined approach of PBM and OMT had a more pronounced impact on diminishing pain and enhancing functional activity in patients with orofacial disorders. One study reported significant increases in pressure pain threshold for TMJ, masseter, and anterior temporalis muscles at both sides in the post-treatment compared with the pre-treatment in both groups. The risk of bias was low in 7, moderate in 2, and high in 1 study. The efficacy of a combined modality treatment of PBM with OMT for orofacial pain disorder shows promising results. However, further randomized controlled trials with extended follow-up periods standardized PBM and OMT parameters are warranted to obtain firm conclusions.

Effect of Lithium on Orthodontic Tooth Movement: a Systematic Review of Animal Studies.

Objective: This study aimed to systematically review the effect of lithium on orthodontic tooth movement (OTM). Methods: The focus question was "does lithium have an effect on OTM?" A systematic search was conducted using indexed databases and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The quality assessment of the selected studies was performed according to the systematic review center for laboratory animal experimentation. Results: Five of the initially identified 656 articles fulfilled the eligibility criteria and were selected for this review. The studies reported that lithium administration lowered the rate of OTM by inducing a reduction in the number of osteoclasts and possibly inhibiting osteoclastogenesis. These studies further showed an increase in bone density and bone volume by promoting the Wnt/ß-catenin signaling pathway and osteoblastogenesis. It was also noted that lithium reduced orthodontically induced root resorption during experimental OTM. Further, standardized studies are warranted to understand the impact of lithium in OTM. Overall, the risk of bias for 3 studies was very high, high in 1 study, and moderate in 1 study. Conclusion: On an experimental level in animals, lithium decreased the rate of OTM during the active treatment phase by increasing bone density and bone volume and reducing root resorption. In addition, lithium may enhance alveolar bone formation during orthodontic retention. Clinically, this may impact the orthodontic treatment duration in patients receiving lithium, and further studies are needed to understand the true impact of lithium on OTM.

Effectiveness of mineral trioxide aggregate on postoperative pain in non-surgical endodontic treatment: a systematic review of randomized controlled trials.

INTRODUCTION: Postoperative endodontic pain can negatively influence the quality of life of the patients. Mineral Trioxide Aggregate (MTA) has gained attention as a potential medicament in various endodontic procedures. MTA has been shown to have desirable properties such as biocompatibility, marginal adaptation, and sealing ability compared to other materials. Limited evidence is available about the effectiveness of MTA on the reduction of postoperative pain following endodontic treatment. This article aimed to compare the non-surgical post-endodontic pain-relieving effect of MTA compared with other materials. METHODS: Indexed databases (PubMed/Medline, EMBASE, OVID, Scopus, and Cochrane) were independently searched for relevant manuscripts published up to and until June 2023. Randomized controlled trials (RCTs) with a focus on teeth with pulp pathologies, with or without radiolucency, requiring primary endodontic treatment were included. Risk of bias across individual studies was performed using the Cochrane risk of bias tool for interventions. RESULTS: Out of the initial 169 articles searched, 9 RCTs met the selection criteria. The protocols were like all the studies, but the pain rating scales, filling material, and restoration materials varied. Out of the 9 included studies, in 4 studies MTA significantly reduced postoperative pain levels, 5 studies showed no difference between MTA and other materials, whereas 1 study reported an adverse effect of grey discoloration after MTA. CONCLUSION: The findings of the present review indicate that MTA may reduce postoperative pain following non-surgical endodontic treatment. However, future standardized studies should be conducted to validate the results.

Lymphoma masquerading as jaw pain, headache, and syncope: A case report.

BACKGROUND: Lymphomas of parapharyngeal space often have complex manifestations, posing a diagnostic dilemma for clinicians. CASE DESCRIPTION: A 64-year-old man sought treatment for a 4-month history of unresolving right-sided headache and jaw pain associated with syncope, all of which started with a toothache. Since the onset of pain, the patient had undergone multiple diagnostic tests with various specialists, with no pain relief. A detailed clinical and radiologic examination by an orofacial pain specialist revealed diffuse large B-cell lymphoma in the parapharynx. PRACTICAL IMPLICATIONS: A thorough knowledge of the head and neck anatomy helps in identifying the pathophysiology of complex orofacial pain manifestations, which assists in early diagnosis and treatment.

Time-Course Progression of Whole Transcriptome Expression Changes of Trigeminal Ganglia Compared to Dorsal Root Ganglia in Rats Exposed to Nerve Injury.

Mechanisms underlying neuropathic pain (NP) are complex with multiple genes, their interactions, environmental and epigenetic factors being implicated. Transcriptional changes in the trigeminal (TG) and dorsal root (DRG) ganglia have been implicated in the development and maintenance of NP. Despite efforts to unravel molecular mechanisms of NP, many remain unknown. Also, most of the studies focused on the spinal system. Although the spinal and trigeminal systems share some of the molecular mechanisms, differences exist. We used RNA-sequencing technology to identify differentially expressed genes (DEGs) in the TG and DRG at baseline and 3 time points following the infraorbital or sciatic nerve injuries, respectively. Pathway analysis and comparison analysis were performed to identify differentially expressed pathways. Additionally, upstream regulator effects were investigated in the two systems. DEG (differentially expressed genes) analyses identified 3,225 genes to be differentially expressed between TG and DRG in naïve animals, 1,828 genes 4 days post injury, 5,644 at day 8 and 9,777 DEGs at 21 days postinjury. A comparison of top enriched canonical pathways revealed that a number of signaling pathway was significantly inhibited in the TG and activated in the DRG at 21 days postinjury. Finally, CORT upstream regulator was predicted to be inhibited in the TG while expression levels of the CSF1 upstream regulator were significantly elevated in the DRG at 21 days postinjury. This study provides a basis for further in-depth studies investigating transcriptional changes, pathways, and upstream regulation in TG and DRG in rats exposed to peripheral nerve injuries. PERSPECTIVE: Although trigeminal and dorsal root ganglia are homologs of each other, they respond differently to nerve injury and therefore treatment. Activation/inhibition of number of biological pathways appear to be ganglion/system specific suggesting that different approaches might be required to successfully treat neuropathies induced by injuries in spinal and trigeminal systems.

The association between migraines and periodontal disease: A systematic review of clinical studies.

BACKGROUND: Recent studies have postulated several hypotheses explaining the association between migraines and periodontitis. We aimed to systematically review and assess if there is an association between inflammatory mediators in migraines and periodontal disease. Indexed database search was performed from inception up to and including April 2022. Data such as study design, study grouping, participants, age, sex, migraine characteristics, assessment criteria for periodontitis and outcomes were collected. Methodological index for non-randomized studies was used to assess the risk of bias. The systematic analysis format was personalized to review the appropriate information. HIGHLIGHTS: Levels of pro-inflammatory mediators such as serum procalcitonin, leptin, calcitonin gene related peptide and interleukin-6 were elevated in patients with chronic periodontitis and migraines. CONCLUSION: Chronic periodontitis may be a contributing factor for migraines. However, future standardized studies are required to understand the true relationship at a clinical and molecular level. This may better help in managing patients with comorbid conditions in the future.

Pathogenesis and Differential Diagnosis of Temporomandibular Joint Disorders.

Temporomandibular disorders (TMDs) are an umbrella term including disorders of the temporomandibular joint and muscles of the masticatory system. They are the most common nonodontogenic cause of pain in the orofacial region. A clear understanding of various conditions, underlying mechanisms, clinical presentation, and examination skills is required to effectively diagnose and manage these patients.

Temporomandibular Joint Disorder Comorbidities.

Comorbidity is a distinct additional condition that either existed or exists during the clinical course of a patient afflicted by the condition/entity in question. The clinician attempting to manage temporomandibular joint disorder (TMD) and TMD pain must realize that recognition and management of the comorbidities are essential to the successful management of the same with optimal pain control. When TMD presents with multiple comorbidities, the task for the clinician becomes more complex. It is the hope of the authors that this condensed version of TMD-associated comorbidities acts as a primer for understanding the significance of the same in pain management.

Effects of intra-nasal melanocortin-4 receptor antagonist on trigeminal neuropathic pain in male and female rats.

Treatment of chronic orofacial pain remains a major therapeutic challenge despite available medications. Melanocortins have been implicated in pathologic pain. Intrathecal administration of MC4R antagonists has been shown to alleviate neuropathic pain (NP) in male rats. However, intrathecal delivery is very invasive and requires surgeon's intervention. Intra-nasal rout offers a non-invasive drug delivery method that can be self-administered making it very attractive clinically. In this study, we investigated the effects of intra-nasally delivered MC4R antagonist (HS014) on trigeminal neuropathic pain (TNP) in male and female rats. We also measured the MC4R protein levels in the trigeminal ganglia (TG) and infraorbital nerve (ION) of rats. We used ION chronic constriction injury (ION-CCI) to induce TNP in rats. We used von Frey and pinprick assays to measure the development of hypersensitivity in the face following ION-CCI. At 22 days post-ION-CCI, we delivered HS014 intra-nasally to measure its effects on TNP in rats. We used enzyme linked immunosorbent assay to measure MC4R protein levels in the TG and ION. ION-CCI resulted in a significant increase of MC4R protein levels in the ipsilateral TG and ION of male and female rats. Intra-nasal delivered HS014 resulted in a significant reduction of ION-CCI induced hypersensitivity in male and female rats. These results demonstrate that intranasal delivery of MC4R antagonist alleviated TNP in male and female rats and suggest that such treatment could be beneficial therapeutically for individuals with chronic NP.

Response profile in a rat model of exercise-induced hypoalgesia is associated with duloxetine, pregabalin and diclofenac effect on constriction-induced neuropathy.

BACKGROUND: Exercise is a known trigger of the inhibitory pain modulation system and its analgesic effect is termed exercise-induced hypoalgesia (EIH). Previous studies have demonstrated that rats with deficient analgesic response following exercise develop more significant hypersensitivity following nerve injury compared to rats with substantial analgesic response following exercise. OBJECTIVES: A rat model of EIH as an indicator of the pain inhibitory system's efficiency was used to explore the association between EIH profiles and the effect of pharmacotherapy on rat's neuropathic pain. METHODS: EIH profiles were assessed by evaluating paw responses to mechanical stimuli before and after exercise on a rotating rod. Rats with a reduction of ≤33% in responses were classified as low EIH and those with ≥67% as high EIH. Low and high EIH rats underwent sciatic nerve chronic constriction injury (CCI). Paw responses to mechanical stimuli were measured at baseline, following CCI, and after treatment with diclofenac, duloxetine or pregabalin. In a different group of low and high EIH rats, EIH was measured before and following treatment with the same medications. RESULTS: Low EIH rats developed more significant hypersensitivity following CCI. Duloxetine and pregabalin successfully reduced hypersensitivity, although significantly more so in low EIH rats. Diclofenac had limited effects, and only on low EIH rats. Four days of duloxetine administration transformed low EIH rats' profiles to high EIH. CONCLUSIONS: The findings of this study suggest that EIH profiles in rats can not only predict the development of hypersensitivity following injury but may also support targeted pharmacological treatment. SIGNIFICANCE: Exercise is a known trigger of the inhibitory pain modulation. Rats with deficient analgesic response following exercise develop more significant hypersensitivity following nerve injury. Pain modulation profiles in rats can also support targeted pharmacological treatment; rats with deficient analgesic response following exercise benefit more from treatment with duloxetine and gabapentin. Treatment with duloxetine can improve pain modulation profile.

Trigeminal Herpes Zoster Transited to Ipsilateral Occipital Neuralgia.

The pain of occipital neuralgia (ON) is thought to be secondary to trauma or injury to the occipital nerve at any point along the course of the nerve. ON may also be caused by an infectious process (herpes zoster) or compression of the nerve. The patient, in this case, presented to our clinic with complaints of occipital pain and rash and swelling of the right lower jaw. One week before presenting to our clinic, the patient developed severe pain in the first division of the trigeminal region with erythema and vesicles. A blood test showed a remarkably high antibody titer for varicella-zoster virus (VZV). The patient was prescribed oral valacyclovir (Valtrex®) (3000 mg/day), which resulted in the complete remission of the rash and blisters in the occipital region. This highlights the importance of considering neuroanatomy of the trigeminal region and cervical nerve.

The relation of temporomandibular disorders and dental occlusion: a narrative review.

OBJECTIVE: The term temporomandibular disorders (TMDs) encompasses a variety of disorders of the temporomandibular joint (TMJD) and the associated musculature (MMD). Occlusion and its role in the genesis of TMDs is one of the most controversial topics in this arena. The objective of the narrative review was to summarize the implications of TMDs and its relationship to dental occlusion in two scenarios: 1) TMD as an etiologic factor in dental occlusal changes; 2) The role of dental occlusion as a causative factor in the genesis of TMDs. DATA SOURCES: Indexed databases were searched from January 1951 to August 2021 using the terms TMJ, TMD, temporomandibular disorders, temporomandibular joint, and dental occlusion. CONCLUSION: There is lack of good primary research evaluating true association and showing the cause-and-effect relationship between dental occlusion and TMD. Systematic reviews suggest that the role of occlusion as a primary factor in the genesis of TMDs is low to very low. However, a variety of TMDs can lead to secondary changes in dental occlusion. Distinction between the two is paramount for successful management.

Hemicrania continua secondary to neurogenic paravertebral tumor- a case report.

OBJECTIVES: Hemicrania continua (HC) is one of the trigeminal autonomic cephalalgias (TAC), where sympathetic dysfunction and autonomic dysfunction resulting in parasympathetic over activation with some evidence of sympathetic inhibition have been suggested as probable causes. However, cases of hemicrania continua secondary to sympathetic dysfunction due to neurogenic paravertebral tumor impinging on the sympathetic chain has not been previously reported. In this case, the probability of the sympathetic dysfunction was more likely based on the clinical features and management. CASE PRESENTATION: A 23-year-old female presented with a chief complaint of right unilateral pain in the retro-bulbar, head and facial region for the past three years. An initial MRI of the brain was negative, whereas an MRI of the spine was advised to rule out a cervicogenic origin of the pain. The MRI revealed a well-defined mass lesion within right paravertebral region at T3 indicative of a neurogenic tumor. The patient was diagnosed with probable hemicrania continua secondary to neurogenic tumor impinging on adjacent sympathetic chain. A trial of indomethacin 75 mg/day was advised, which provided complete relief of the headache. The patient was referred to a neurologist for management of the neurogenic tumor. CONCLUSIONS: Headache disorders may be secondary to pathologies and comprehensive evaluation and accurate diagnosis are essential. Knowledge of neuroanatomy is paramount to understand and explain underlying pathophysiological mechanisms. Multidisciplinary management is essential in complex orofacial cases.

The role of the dentist in the diagnosis and management of pediatric obstructive sleep apnea.

The objective of this article is to review the role of the dentist in the early diagnosis of pediatric obstructive sleep apnea (OSA) and to provide an in-depth review of the best evidence-based practices available to treat and/or to refer these patients for intervention. MATERIAL AND METHODS: A narrative review was performed using indexed data bases (PubMed, Medline, EMBASE, OVID, Scopus and Cochrane) up to year 2020, and approximately 1000 articles were reviewed. The articles included were those with the best information provided. RESULTS: Detailed review of the literature suggests that the role of the dentist has been redefined owing to their expertise in the orofacial region. Every patient consulting a dental practice is not merely a dental patient; he/she also requires a comprehensive medical review. The role of the dentist is pivotal in pediatric patients once diagnosed with OSA; as the patients grow, growth modification can be achieved, and future management will be easier. Initiating dental treatments during growth can benefit patients two-fold, saving them from malocclusion, and intervening in orofacial structural growth can help to avoid cumbersome treatments, such as CPAP and various surgeries. Proper diagnosis and management of systemic illnesses can prevent compromised quality of life, delays in treatment, morbidity and, in some cases, mortality.

Myofascial pain in temporomandibular disorders: Updates on etiopathogenesis and management.

OBJECTIVES: Temporomandibular disorders (TMDs) are an umbrella term encompassing disorders of both the temporomandibular joint (TMJD) and masticatory musculature (MMD). The objective of this review is to provide an overview of the etiopathogenesis, clinical features and diagnosis of MMD, and to summarize the current trends in the therapeutic management. METHODS: A review of the literature was performed from 1985 to 2020. The keywords included were "temporomandibular disorders OR temporomandibular joint disorders" AND "myofascial pain OR masticatory myofascial pain OR trigger point". A total of 983 articles were screened with abstracts and approximately 500 full text articles were included in the review based on their relevance to the topic. RESULTS: MMD's present significant challenges in diagnosis and treatment. Effective treatment requires a clear diagnosis based on an understanding of pathophysiologic mechanisms, a detailed history with assessment of predisposing local and systemic factors, perpetuating factors, a comprehensive clinical evaluation and a diagnostic workup. CONCLUSION: A thorough history and clinical examination are the gold standards for diagnosis of MMD. Serological testing may help identify underlying co-morbidities. Recent diagnostic modalities including ultrasound sonoelastography and magnetic resonance elastography (MRE) have shown promising results. The treatment goals for MMD are to control pain, restore mandibular function and facilitate the return to normal daily activity and improve the overall quality of life of a patient. Conservative modalities including home care regimens, pharmacotherapy, intraoral appliance therapy, local anesthetic trigger point injections, physiotherapy and complementary modalities may be beneficial in patients with MMD's.

Diagnostic Tool Using the Diagnostic Criteria for Temporomandibular Disorders: A Randomized Crossover-Controlled, Double-Blinded, Two-Center Study.

AIMS: To assess the speed and accuracy of a checklist user interface for the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). METHODS: A diagnostic tool formatted as a checklist was developed and compared to an existing diagnostic tool, the DC/TMD diagnsostic decision trees. Both types of tools use the DC/TMD and were tested by dental students, interns, and residents in the USA and Japan for diagnosis of hypothetical patients. The comparisons were done in a randomized, crossover, controlled, double-blinded trial. RESULTS: Overall, subjects using the experimental tool answered 25% more correct diagnoses (P < .001) and missed 27% fewer diagnoses (P < .01). They were also able to finalize their diagnoses faster than those using the control tool, in 16% less time (P < .05). The difference in accuracy was more pronounced in complex cases, while the difference in speed was more pronounced in simple cases. CONCLUSION: This checklist is an alternative user interface for the DC/TMD.

Exercise-Induced Hypoalgesia Profile in a Rat Neuropathic Pain Model Predicts Pain Severity Following Infraorbital Nerve Injury and Is Associated with Local Cytokine Levels, Systemic Endocannabinoids, and Endogenous Opioids.

AIMS: To investigate the role of exercise-induced hypoalgesia (EIH) in the development of neuropathic pain (NP) following infraorbital nerve (ION) injury and to explore possible underlying mechanisms defining the differences between rats with high and low EIH. METHODS: EIH was evaluated by measuring the percentage of withdrawal responses to a series of 30 mechanical stimuli applied to the hind paw before and after 180 seconds of exercise on a rotating rod. The rats were assigned to low- and high-EIH groups based on reduction in the percent of withdrawal responses following exercise. NP was induced in high- and low-EIH rats via ION constriction injury. Rats were tested with graded nylon monofilaments to establish the withdrawal threshold. Increasingly stiff monofilaments were applied to the ION territory until there was a clear withdrawal by the rat. This was repeated a total of three times. A decreased withdrawal threshold indicates allodynia. Testing was performed at baseline and at 3, 10, and 17 days following the injury. On day 17 postinjury, IONs were harvested for the assessment of interleukin (IL)-6, IL-1ß, and IL-10 levels. Samples from high-EIH and low-EIH surgically naïve rats served as control for the cytokines study. In this second part of the study, the effects of cannabinoid 1 (CB1) and cannabinoid 2 (CB2) antagonists and naltrexone on EIH profiles and on the withdrawal thresholds to mechanical stimulation were measured. EIH and withdrawal thresholds in high- and low-EIH rats were measured before and after administration of antagonists. RESULTS: Low-EIH rats developed significantly more pronounced allodynia in the ION territory following injury compared to high-EIH rats. At 17 days postinjury, ION IL-1ß levels were higher in low-EIH rats, and IL-10 levels were higher in high-EIH rats. CB1 antagonist blocked the analgesic effect induced by exercise in high- but not in low-EIH rats. The CB2 antagonist had no significant effect on high- or low-EIH rats. Naltrexone blocked the effects of EIH in both high- and low-EIH rats. Exercise induced a significant analgesic effect in high-EIH but not in low-EIH rats. CB1 or CB2 antagonist administration had no effect on pre-exercise responses to mechanical stimulation, while naltrexone administration resulted in significant allodynia in both low- and high-EIH rats. CONCLUSION: This study demonstrated substantial differences between rats with high and low EIH. The results suggest that following ION injury, high-EIH rats may have a more prominent or activated endocannabinoids system and that their inflammatory response is moderated, with higher levels of IL-10 and lower levels of IL-1ß.

Genetic variation in catechol-O-methyltransferase is associated with individual differences in conditioned pain modulation in healthy subjects.

BACKGROUND: Genetic variation in the catechol-O-methyltransferase (COMT) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is conditioned pain modulation (CPM). We hypothesized that variation in CPM may have a genetic basis. METHODS: We evaluated CPM in 77 healthy pain-free Caucasian subjects by applying repeated mechanical stimuli to the dominant forearm using 26-g von Frey filament as the test stimulus with immersion of the non-dominant hand in hot water as the conditioning stimulus. We assayed COMT SNP genotypes by the TaqMan method using DNA extracted from saliva. RESULTS: SNP rs4680 (val158 met) was not associated with individual differences in CPM. However, CPM was associated with COMT low pain sensitivity haplotypes under an additive model (p = 0.004) and the effect was independent of gender. CONCLUSIONS: We show that, although four SNPs are used to infer COMT haplotypes, the low pain sensitivity haplotype is determined by SNP rs6269 (located in the 5' regulatory region of COMT), suggesting that inherited variation in gene expression may underlie individual differences in pain modulation. Analysis of 13 global populations revealed that the COMT low pain sensitivity haplotype varies in frequency from 13% to 44% and showed that two SNPs are sufficient to distinguish all COMT haplotypes in most populations.