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.

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.

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.

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.

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.

Hypericum perforatum (St. John's Wort) as a possible therapeutic alternative for the management of trigeminal neuralgia (TN) - A case report.

Hypericum perforatum (St. John's Wort) is an alternative remedy used primarily for depression but also is used for rheumatism, gastroenteritis, headache and neuralgias. The mechanism of action of Hypericum perforatum comprehends a neurotransmitter inhibitory profile, and potential anti-inflammatory and anti-oxidant effects suggesting a role for pain management.

Current and novel insights into the neurophysiology of migraine and its implications for therapeutics.

Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses.

Cancer and Referred Facial Pain.

Orofacial pain may be a symptom of diverse types of cancers as a result of local or distant tumor effects. The pain can be presented with the same characteristics as any other orofacial pain disorder, and this should be recognized by the clinician. Orofacial pain also can arise as a consequence of cancer therapy.

A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity.

Update on animal models of migraine.

Migraine is a severe and debilitating disorder of the brain that involves a constellation of neurological symptoms alongside head pain. Its pathophysiology is only beginning to be understood, and is thought to involve activation and sensitization of trigeminovascular nociceptive pathways that innervate the cranial vasculature, and activation of brain stem nuclei. Much of our understanding of migraine pathophysiology stems from research conducted in animal models over the last 30 years, and the development of unique assays in animals that try to model specific aspects of migraine pathophysiology related to particular symptoms.

Orofacial pain management: current perspectives.

Some of the most prevalent and debilitating pain conditions arise from the structures innervated by the trigeminal system (head, face, masticatory musculature, temporomandibular joint and associated structures). Orofacial pain (OFP) can arise from different regions and etiologies. Temporomandibular disorders (TMD) are the most prevalent orofacial pain conditions for which patients seek treatment.

Insights into the pharmacological targeting of the trigeminocervical complex in the context of treatments of migraine.

Migraine is one of the most severe and debilitating brain disorders. Most scientists accept that it involves activation and sensitization of the trigeminovascular system, which includes the sensory peripheral projections to the pain-producing dura mater, and a central projection to the trigeminal nucleus caudalis and its cervical extension, the trigeminocervical complex (TCC). The development of the anti-migraine therapeutics, triptans-5-HT1B/1D receptor agonists, had originally targeted the craniovasculature to exert therapeutic effects, and this locus of action seemed to predict efficacy in the clinic.

Pearls and pitfalls in experimental in vivo models of headache: conscious behavioral research.

Background: Physiological studies have been determinant for the understanding of migraine pathophysiology and the screening of novel therapeutics. At present, there is no animal model that translates fully the clinical symptoms of migraine, and generally these studies are conducted on anesthetized animals.

Methodology: Pain as well as non-painful symptoms such as photophobia, need to have a conscious individual to be experienced; therefore, the new development and adaptation of behavioral assays assessing pain and other non-painful symptomatology in conscious animals represents a great opportunity for headache research and it is exciting that more and more researchers are using behavioral paradigms.