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.

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.

Burning mouth syndrome: a review of etiology, diagnosis, and management.

Burning mouth syndrome (BMS) is a chronic condition characterized by a burning sensation of the oral cavity and is often associated with taste disturbances and xerostomia. It primarily affects menopausal or postmenopausal women. Idiopathic or primary BMS can occur spontaneously and without any identifiable precipitating factors.

Mucocutaneous Diseases: Oral Lichen Planus, Mucous Membrane Pemphigoid and Pemphigus Vulgaris.

Mucocutaneous diseases affect the oral cavity and can present a diagnostic challenge. They can have systemic involvement, necessitating multidisciplinary management. Frequently, patients will see their general dentists initially for evaluation.

Differentiation by NK cells is a prerequisite for effective targeting of cancer stem cells/poorly differentiated tumors by chemopreventive and chemotherapeutic drugs.

Natural Killer (NK) cells target oral, pancreatic, lung, breast, glioblastoma and melanoma stem-like/poorly differentiated tumors. Differentiation of the abovementioned tumors with supernatants from split-anergized NK cells decreases their susceptibility to NK cells, but increases their sensitivity to cisplatin (CDDP)-mediated cell death. Breast and melanoma tumor cells with CD44 knockdown display enhanced susceptibility to NK cell-mediated lysis, potentially due to decreased differentiation.

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.

Increased lysis of stem cells but not their differentiated cells by natural killer cells; de-differentiation or reprogramming activates NK cells.

The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-gamma were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells.

Prevalence of hypertension in patients with trigeminal neuralgia.

It is unclear whether hypertension (HTN) is a predisposing factor for the development of trigeminal neuralgia (TN). The purpose of this study was to determine the prevalence of HTN in TN patients and controls at the USC Orofacial Pain and Oral Medicine Center. A retrospective chart review was conducted from a database of over 3,000 patient records from 2003 to 2007.

Cluster headache and obstructive sleep apnea: are they related disorders?

Patients with cluster headache (CH) have a higher prevalence of sleep apnea, and a possible relationship between these two conditions has been proposed. Although patients suffering from CH attacks often wake up from sleep, sleep apnea has been suggested to be a trigger or an associated abnormality in CH. It has been proposed that regulation of the hypothalamus may be responsible for sleep apnea, and that similiarly CH is generated in the hypothalamus.

Clinical characteristics and diagnosis of atypical odontalgia: implications for dentists.

Background: Atypical odontalgia (AO) is a poorly understood and commonly misdiagnosed condition for which patients often undergo multiple unsuccessful dental or surgical procedures. The authors conducted a study to determine the prevalence and describe the characteristics of patients with AO seen at the University of Southern California Orofacial Pain and Oral Medicine Center (USC OFP-OM Center), Los Angeles.

Methods: The authors conducted a retrospective record review from a database of more than 3,000 patient records from June 2003 to August 2007 to identify patients diagnosed with AO.

Rapid and potent induction of cell death and loss of NK cell cytotoxicity against oral tumors by F(ab')2 fragment of anti-CD16 antibody.

Freshly isolated untreated NK cells undergo rapid apoptosis and lose their cytotoxic function upon the addition of F(ab')2 fragment of anti-CD16 antibodies. Loss of NK cell cytotoxic function after treatment with F(ab')2 fragment of anti-CD16 antibody can be seen against K562 and UCLA-2 oral tumor cells when either added immediately in the co-cultures of NK cells with the tumor cells or after pre-treatment of NK cells with the antibody before their addition to the tumor cells. Addition of Interleukin-2 (IL-2) in combination with anti-CD16 antibody to NK cells delayed the induction of DNA fragmentation in NK cells, and even though decreased cytotoxicity could still be observed against K562 and UCLA-2 oral tumors when compared to IL-2 alone treated NK cells, the cytotoxicity levels remained relatively higher and approached those obtained by untreated NK cells in the absence of antibody treatment.

Potential contribution of naïve immune effectors to oral tumor resistance: role in synergistic induction of VEGF, IL-6, and IL-8 secretion.

The aim of this study is to identify the phenotype of resistant oral tumors, and to delineate the contribution of immune effectors to resistance of oral tumors. UCLA-1 oral tumors which were resistant to NK cell mediated cytotoxicity secreted increased amounts of IL-6, IL-1beta, GM-CSF, and IL-8 when cultured with or without immune effectors. In addition, the levels of vascular endothelial growth factor (VEGF) secretion in the co-cultures of naïve immune effectors with UCLA-1 rose significantly when compared to tumor cells alone.

Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and induces apoptotic death of naive natural killer cells.

Down-modulation of CD16 (FcgammaRIII) receptors and loss of natural killer (NK) cell function have been observed in oral cancer patients. However, neither the mechanisms nor the significance of the decrease in CD16 receptors have been fully understood. The cytotoxic activity and survival of NK cells are negatively regulated by antibodies directed against CD16 surface receptor.

Inhibition of nuclear factor kappa B (NFkappaB) activity in oral tumor cells prevents depletion of NK cells and increases their functional activation.

The aim of this study is to identify candidate factors which may be responsible for the functional inactivation and depletion of NK cells by tumor cells. Inhibition of NFkappaB activity by an IkappaB super-repressor in HEp2 cells, a cell line commonly used as an oral tumor model, blocked tumor-induced NK cell death, and increased the function of NK cells significantly. Increased expression of CD69 early activation antigen on NK cells as well as augmented proliferation and secretion of IFN-gamma by NK cells were observed when these cells were co-incubated with IkappaB super-repressor transfected HEp2 cells (HEp2-IkappaB((S32AS36A))).

Cytokine dependent inverse regulation of CD54 (ICAM1) and major histocompatibility complex class I antigens by nuclear factor kappaB in HEp2 tumor cell line: effect on the function of natural killer cells.

The aim of this study is to investigate the mechanisms by which elevated nuclear factor kappaB (NFkappaB) activity in HEp2 cells can modulate the function and survival of immune effector cells. Inhibition of NFkappaB functional activity by stable expression of IkappaB super-repressor rendered HEp2 cells (HEp2-IkappaB((S32AS36A))) susceptible to natural killer (NK) cell mediated cytotoxicity. Increase in surface ICAM1 expression was greater on HEp2-IkappaB((S32AS36A)) cells than on the surface of vector alone transfected HEp2 cells when these cells were treated with IFN-gamma.