Salivary stimulatory effect of novel low level transcutaneous electro neurostimulator in geriatric patients with xerostomia.

BACKGROUND: Xerostomia (dryness of the mouth) is one of the most common long-term consequences of ageing, and it causes a tremendous impact on the function and morphology of the salivary ductal system. As a consequence, it leads to a decrease in the amount of salivary output and also affects the overall quality of life. The purpose of this study was to determine whether electrostimulation using a custom designed transcutaneous electrical nerve stimulation (TENS) device will help to improve the quality of secreted saliva following electrostimulation. METHODS: One hundred thirty-five participants underwent the intervention for three months, twice daily (80 Hz). Pre-intervention and post-intervention unstimulated saliva were collected. Parameters such as salivary pH, cortisol level, salivary antioxidants, total protein, the viscosity of saliva, and microbial carriage were analysed. RESULTS: Salivary pH, cortisol, microbial cultures, viscosity, and antioxidants showed a significant difference at the end of the 3rd month (p < 0.05). Irrespective of the patient's age, gender, and common underlying systemic illnesses (diabetes and hypertension), a significant change in the quality of the salivary analytes was observed. CONCLUSION: The study emphasises the use of a custom designed TENS device in improving the quality of secreted saliva among old patients with oral dryness.

Targeted Therapy for Orofacial Pain: A Novel Perspective for Precision Medicine.

Orofacial pain (OFP) is a dental specialty that includes the diagnosis, management and treatment of disorders of the jaw, mouth, face, head and neck. Evidence-based understanding is critical in effectively treating OFPs as the pathophysiology of these conditions is multifactorial. Since OFP impacts the quality of life of the affected individuals, treating patients successfully is of the utmost significance. Despite the therapeutic choices available, treating OFP is still quite challenging, owing to inter-patient variations. The emerging trends in precision medicine could probably lead us to a paradigm shift in effectively managing the untreatable long-standing pain conditions. Precision medicine is designed based on the patient's genetic profile to meet their needs. Several significant relationships have been discovered based on the genetics and genomics of pain in the past, and some of the notable targets are discussed in this review. The scope of this review is to discuss preclinical and clinical trials that include approaches used in targeted therapy for orofacial pain. Future developments in pain medicine should benefit from current trends in research into novel therapeutic approaches.

Identification of microRNA Signatures in Peripheral Blood of Young Women as Potential Biomarkers for Metal Allergy.

MicroRNA (miRNA) is a short (19-24 nucleotide) endogenous non-protein RNA that exists in the body and controls the translation process from genes to proteins. It has become useful as a diagnostic tool and a potential treatment target in cancer research. To explore the function of miRNA in contact dermatitis, female participants with a positive metal allergy diagnosis (n = 3) were enrolled along with additional female participants with no medical history of metal allergy (n = 3). A patch test was performed on each participant. Peripheral blood was collected from all the participants before the patch test and at days 3 and 7 after starting the patch test. After total RNA was obtained from peripheral blood leukocytes and cDNA was generated, microarray analysis was performed to analyze the large-scale circulating miRNA profile. Real-time polymerase chain reaction (RT-PCR) was then used to clarify the overall target miRNA expression. Downregulation of hsa-let-7d-5p, hsa-miR-24-3p, hsa-miR-23b-3p, hsa-miR-26b-5p, and hsa-miR-150-5p was found on day 7. Certain miRNAs were confirmed using RT-PCR. These peripheral blood miRNAs could be diagnostic biomarkers for metal allergies.

Mechanism and clinical use of botulinum neurotoxin in head and facial region.

PURPOSE: Botulinum neurotoxin (BoNT) is a biological toxin produced by Clostridium botulinum. BoNT is a potent toxin extensively used in therapeutic interventions. This review provides an updated overview of the mechanisms of action and clinical applications of BoNT in head and facial region. STUDY SELECTION: MEDLINE/PubMed searches were conducted using the terms "botulinum neurotoxin" and "dentistry" along with a combination of other related terms. In addition, studies were manually selected from reference lists of the selected articles. RESULTS: The Food and Drug Administration in the United States initially approved BoNT to treat strabismus, blepharospasm, and hemifacial spasms. The use of BoNT in dermatology and cosmetics has been widely established and has created a revolution in these fields. Over the years, its applications in various medical specialties have expanded widely. Owing to its safety, efficacy, and long duration of action, it is well-accepted by patients. BoNT/A and BoNT/B are widely used in clinical practice. Several off-label uses of BoNT in the dental fraternity have yielded promising results. We have elaborated on the speculated mechanism of action, dosage, effective sites of injection, and adverse effects of each therapeutic application. The various clinical indications for BoNT include bruxism, myofascial pain, temporomandibular joint dislocation, hemifacial pain, orofacial dystonia, facial paralysis, chronic migraine, and trigeminal neuralgia. CONCLUSIONS: BoNT is a safe treatment that can be used effectively, provided that the clinician has adequate knowledge regarding the mechanism, injection techniques, and local and systemic side effects and that it is administered cautiously and purposefully.

Analgesic Effect of Tranilast in an Animal Model of Neuropathic Pain and Its Role in the Regulation of Tetrahydrobiopterin Synthesis.

Trigeminal neuralgia is unilateral, lancinating, episodic pain that can be provoked by routine activities. Anticonvulsants, such as carbamazepine, are the drugs of choice; however, these possess side-effects. Microvascular decompression is the most effective surgical technique with a higher success rate, although occasionally causes adverse effects. The potential treatment for this type of pain remains unmet. Increased tetrahydrobiopterin (BH4) levels have been reported in association with axonal injury. This study aimed to evaluate the effect of tranilast on relieving neuropathic pain in animal models and analyze the changes in BH4 synthesis. Neuropathic pain was induced via infraorbital nerve constriction. Tranilast, carbamazepine, or saline was injected intraperitoneally to assess the rat's post-intervention pain response. In the von Frey's test, the tranilast and carbamazepine groups showed significant changes in the head withdrawal threshold in the ipsilateral whisker pad area. The motor coordination test showed no changes in the tranilast group, whereas the carbamazepine group showed decreased performance, indicating impaired motor coordination. Trigeminal ganglion tissues were used for the PCR array analysis of genes that regulate the BH4 pathway. Downregulation of the sepiapterin reductase (Spr) and aldoketo reductase (Akr) genes after tranilast injection was observed compared to the pain model. These findings suggest that tranilast effectively treats neuropathic pain.

Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model.

Peripheral nerve injury leads to sensory ganglion hyperexcitation, which increases neurotransmitter release and neuropathic pain. Botulinum toxin type A (BoNT/A) regulates pain transmission by reducing neurotransmitter release, thereby attenuating neuropathic pain. Despite multiple studies on the use of BoNT/A for managing neuropathic pain in the orofacial region, its exact mechanism of transport remains unclear. In this study, we investigated the effects of BoNT/A in managing neuropathic pain in two different animal models and its transport mechanism in the trigeminal nerve. Intraperitoneal administration of cisplatin induced bilateral neuropathic pain in the orofacial region, reducing the head withdrawal threshold to mechanical stimulation. Unilateral infraorbital nerve constriction (IONC) also reduced the ipsilateral head withdrawal threshold to mechanical stimulation. Unilateral peripheral administration of BoNT/A to the rat whisker pad attenuated cisplatin-induced pain behavior bilaterally. Furthermore, contralateral peripheral administration of BoNT/A attenuated neuropathy-induced behavior caused by IONC. We also noted the presence of BoNT/A in the blood using the mouse bioassay. In addition, the Alexa Fluor-488-labeled C-terminal half of the heavy chain of BoNT/A (BoNT/A-Hc) was localized in the neurons of the bilateral trigeminal ganglia following its unilateral administration. These findings suggest that axonal and hematogenous transport are involved in the therapeutic effects of peripherally administered BoNT/A in the orofacial region.

Dentin-Pulp Complex Tissue Regeneration via Three-Dimensional Cell Sheet Layering.

The dentin-pulp complex is a unique structure in teeth that contains both hard and soft tissues. Generally, deep caries and trauma cause damage to the dentin-pulp complex, and if left untreated, this damage will progress to irreversible pulpitis. The aim of this study was to fabricate a layered cell sheet composed of rat dental pulp (DP) cells and odontogenic differentiation of pulp (OD) cells and to investigate the ability to regenerate the dentin-pulp complex in a scaffold tooth. We fabricated two single cell sheets composed of DP cells (DP cell sheet) or OD cells (OD cell sheet) and a layered cell sheet made by layering both cells. The characteristics of the fabricated cell sheets were analyzed using light microscopy, scanning electron microscope (SEM), hematoxylin-eosin (HE) staining, and immunohistochemistry (IHC). Furthermore, the cell sheets were transplanted into the subrenal capsule of immunocompromised mice for 8 weeks. After this, the regenerative capacity to form dentin-like tissue was evaluated using micro-computed tomography (micro-CT), HE staining, and IHC. The findings of SEM and IHC confirmed that layered cell sheets fabricated by stacking OD cells and DP cells maintained their cytological characteristics. Micro-CT of layered cell sheet transplants revealed a mineralized capping of the access cavity in the crown area, similar to that of natural dentin. In contrast, the OD cell sheet group demonstrated the formation of irregular fragments of mineralized tissue in the pulp cavity, and the DP cell sheet did not develop any hard tissue. Moreover, bone volume/tissue volume (BV/TV) showed a significant increase in hard tissue formation in the layered cell sheet group compared with that in the single cell sheet group (p < 0.05). HE staining also showed a combination of soft and hard tissue formation in the layered cell sheet group. Furthermore, IHC confirmed that the dentin-like tissue generated from the layered cell sheet expressed characteristic markers of dentin but not bone equivalent to that of a natural tooth. In conclusion, this study demonstrates the feasibility of regenerating dentin-pulp complex using a bioengineered tissue designed to simulate the anatomical structure. Impact statement The dentin-pulp complex can be destroyed by deep caries and trauma, which may cause pulpitis and progress to irreversible pulpitis, apical periodontitis, and even tooth loss. Current treatments cannot maintain pulp health, and teeth can become brittle. We developed a three-dimensional (3D) layered cell sheet using dental pulp cells and odontogenic differentiation of pulp cells for dentin-pulp complex regeneration. Our layered cell sheet enables the regeneration of an organized 3D dentin-pulp-like structure comparable with that of natural teeth. This layered cell sheet technology may contribute to dentin-pulp complex regeneration and provide a novel method for complex tissue engineering.