Orofacial Pain.

Objective: This article explores the multiple etiologies, diagnosis, and management of orofacial pain.

Latest Developments: Published in 2019, the International Classification of Orofacial Pain has become the internationally accepted classification system for primary and secondary facial pain. New discoveries in temporomandibular disorders have demonstrated that they are far more complex than the traditional dental mechanistic point of view.

Catalytic enantioselective synthesis of 2-pyrazolines one-pot condensation/6π-electrocyclization: 3,5-bis(pentafluorosulfanyl)-phenylthioureas as powerful hydrogen bond donors.

A new conjugate-base-stabilized carboxylic acid (CBSCA) containing a 3,5-bis(pentafluorosulfanyl)phenylthiourea functionality catalyses challenging one-pot condensations/6π-electrocyclizations of hydrazines and α,β-unsaturated ketones under mild conditions. Structurally diverse -aryl 2-pyrazolines are obtained in good yields and enantioselectivities. The superior performance of 3,5-bis(SF)phenylthioureas over the widely used 3,5-bis(CF)phenylthioureas is further demonstrated in the Michael addition of dimethyl malonate to nitrostyrene, using a new Takemoto-type catalyst.

Trigeminal neuralgia.

Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors.

Temporomandibular Disorders, Bruxism and Headaches.

Temporomandibular disorders (TMDs) and headache disorders are highly prevalent in the population. TMDs can present headache symptoms as a secondary headache and, in addition, be comorbid with primary headache disorders. This overlap has significant clinical implications for which it is essential for the physician to be aware, and they should screen for the potential presence of TMDs in a headache patient.

[Usefulness of e-consultation in cardiology].

Introduction And Objectives: The development of IT tools and interlevel relationships in the management of the most prevalent processes has led to a semi-presential assessment approach. In cardiology, this form of assessment is possible through a close collaboration with primary care. The aim of this study is to analyze the results of our e-consultation program and to establish the effectiveness of this new form of assistance.

Mechanism of a Dually Catalyzed Enantioselective Oxa-Pictet-Spengler Reaction and the Development of a Stereodivergent Variant.

Enantioselective oxa-Pictet-Spengler reactions of tryptophol with aldehydes proceed under weakly acidic conditions utilizing a combination of two catalysts, an indoline HCl salt and a bisthiourea compound. Mechanistic investigations revealed the roles of both catalysts and confirmed the involvement of oxocarbenium ion intermediates, ruling out alternative scenarios. A stereochemical model was derived from density functional theory calculations, which provided the basis for the development of a highly enantioselective stereodivergent variant with racemic tryptophol derivatives.

PACAP-38 related modulation of the cranial parasympathetic projection: A novel mechanism and therapeutic target in severe primary headache.

Background And Purpose: Little is known of how cranial autonomic symptoms (CAS) in cluster headache and migraine may contribute to their severe headache phenotype. This strong association suggests the involvement of the cranial parasympathetic efferent pathway. To investigate its contribution, we studied the role of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), a potent sensory and parasympathetic neuropeptide, in modulating pre- and post-ganglionic cranial parasympathetic projection neurons, and their influence on headache-related trigeminal-autonomic responses.

Pharmacological Management of Orofacial Pain.

Orofacial pain is a category of complex disorders, including musculoskeletal, neuropathic and neurovascular disorders, that greatly affect the quality of life of the patient. These disorders are within the fields of dentistry and medicine and management can be challenging, requiring a referral to an orofacial pain specialist, essential for adequate evaluation, diagnosis, and care. Management is specific to the diagnosis and a treatment plan is developed with diverse pharmacological and non-pharmacological modalities.

An Update on Temporomandibular Disorders (TMDs) and Headache.

Purpose Of Review: To provide an overview and highlight recent updates in temporomandibular disorders (TMDs) and their comorbidity with headache disorders regarding pathophysiology and management.

Recent Findings: In the last decade, there have been great advancements in the understanding of TMDs and their relationship with neurovascular pains such as headaches. Understanding of TMDs is necessary for the context of its comorbidity with primary headache disorders.

Nitroglycerin as a model of migraine: Clinical and preclinical review.

Migraine stands as one of the most disabling neurological conditions worldwide. It is a disorder of great challenge to study given its heterogeneous representation, cyclic nature, and complexity of neural networks involved. Despite this, clinical and preclinical research has greatly benefitted from the use of the nitric oxide donor, nitroglycerin (NTG), to model this disorder, dissect underlying mechanisms, and to facilitate the development and screening of effective therapeutics.

Fluorescence Quenching of Xanthene Dyes during Amide Bond Formation Using DMTMM.

Fluorophore bioconjugation to proteins, nucleic acids, and other important molecules can provide a powerful approach to sensing, imaging, and quantifying chemical and biological processes. One of the most prevalent methods for fluorophore attachment is through the formation of amide bonds, which are often facilitated by coupling agents to activate carboxylic acid moieties for subsequent nucleophilic attack by amines. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM) is among the most popular of these coupling agents for bioconjugation due to its ability to facilitate amide bond formation in water.

Combating small molecule environmental contaminants: detection and sequestration using functional nucleic acids.

Small molecule contaminants pose a significant threat to the environment and human health. While regulations are in place for allowed limits in many countries, detection and remediation of contaminants in more resource-limited settings and everyday environmental sources remains a challenge. Functional nucleic acids, including aptamers and DNA enzymes, have emerged as powerful options for addressing this challenge due to their ability to non-covalently interact with small molecule targets.

Interplay of Oral, Mandibular, and Facial Disorders and Migraine.

Purpose Of The Review: Migraine and other primary headache disorders can be localized in the face resembling facial or dental pain, indicating the influence of the trigeminovascular system in the structures innervated by the maxillary (V2) and mandibulary (V3) branches of the trigeminal nerve. Disorders of oral and craniofacial structures may influence primary headache disorders. In the current article, we review the potential links of this interplay.

Magnetic resonance imaging in patients with cardiac implantable electronic devices: A prospective study.

Background: The number of patients with cardiac implantable electronic devices in whom magnetic resonance imaging (MRI) is indicated is constantly increasing. The potential risk of electromagnetic interference has limited its use and it is still contraindicated by the Food and Drug Administration in some cases. The aim of this study is to evaluate the safety and efficacy of MRI in these patients.

Sequestration and Removal of Multiple Small-Molecule Contaminants Using an Optimized Aptamer-Based Ultrafiltration System.

Small-molecule toxins pose a significant threat to human health and the environment, and their removal is made challenging by their low molecular weight. Aptamers show promise as affinity reagents for binding these toxins, and recently, aptamers have been utilized for both sensing and remediation applications. We found that functionalization of ultrafiltration membranes with aptamers provides a convenient scaffold for toxin sequestration, but our initial efforts in this area were limited by low functionalization efficiencies and the ability to only capture a single target molecule.

Targeting reactive nitroxidative species in preclinical models of migraine.

Background: Reactive nitroxidative species, such as nitric oxide but particularly peroxynitrite, have been strongly implicated in pain mechanisms. Targeting peroxynitrite is anti-nociceptive in pain models, but little is known about its role in migraine mechanisms. Given the need to validate novel targets for migraine headache, our objective was to study the potential of reactive nitroxidative species, particularly peroxynitrite, as novel targets for drug discovery and their role in migraine mechanisms.

Glia and Orofacial Pain: Progress and Future Directions.

Orofacial pain is a universal predicament, afflicting millions of individuals worldwide. Research on the molecular mechanisms of orofacial pain has predominately focused on the role of neurons underlying nociception. However, aside from neural mechanisms, non-neuronal cells, such as Schwann cells and satellite ganglion cells in the peripheral nervous system, and microglia and astrocytes in the central nervous system, are important players in both peripheral and central processing of pain in the orofacial region.

Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease.

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls.

Therapeutic targeting of nitroglycerin-mediated trigeminovascular neuronal hypersensitivity predicts clinical outcomes of migraine abortives.

Cranial hypersensitivity is a prominent symptom of migraine, exhibited as migraine headache exacerbated with physical activity, and cutaneous facial allodynia and hyperalgesia. The underlying mechanism is believed to be, in part, activation and sensitization of dural-responsive trigeminocervical neurons. Validated preclinical models that exhibit this phenotype have great utility for understanding putative mechanisms and as a tool to screen therapeutics.

Preclinical studies investigating the neural mechanisms involved in the co-morbidity of migraine and temporomandibular disorders: the role of CGRP.

Background And Purpose: Temporomandibular disorders (TMD) and migraine can be co-morbid. This can be a significant factor in exacerbating and increasing the prevalence of migraine-like symptoms. However, the underlying mechanisms involved are unknown.

Nitroglycerine triggers triptan-responsive cranial allodynia and trigeminal neuronal hypersensitivity.

Cranial allodynia associated with spontaneous migraine is reported as either responsive to triptan treatment or to be predictive of lack of triptan efficacy. These conflicting results suggest that a single mechanism mediating the underlying neurophysiology of migraine symptoms is unlikely. The lack of a translational approach to study cranial allodynia reported in migraine patients is a limitation in dissecting potential mechanisms.

Brain structure and function related to headache: Brainstem structure and function in headache.

Objective: To review and discuss the literature relevant to the role of brainstem structure and function in headache.

Background: Primary headache disorders, such as migraine and cluster headache, are considered disorders of the brain. As well as head-related pain, these headache disorders are also associated with other neurological symptoms, such as those related to sensory, homeostatic, autonomic, cognitive and affective processing that can all occur before, during or even after headache has ceased.

Targeting the central projection of the dural trigeminovascular system for migraine prophylaxis.

Migraine abortives likely target both peripheral-dural and central trigeminovascular mechanisms in mediating their therapeutic effects. However, in preclinical assays, many migraine preventives have little success at inhibiting similar trigeminovascular-mediated peripheral changes within the dural microenvironment. In addition, their effects on central trigeminovascular neuronal responses are largely unknown.

Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache.

Vagus nerve stimulation (VNS) has been reported to be effective in the abortive treatment of both migraine and cluster headache. Using validated animal models of acute dural-intracranial (migraine-like) and trigeminal-autonomic (cluster-like) head pain we tested whether VNS suppresses ongoing and nociceptive-evoked firing of trigeminocervical neurons to explain its abortive effects in migraine and cluster headache. Unilateral VNS was applied invasively via hook electrodes placed on the vagus nerve.