Project description:Clinical and basic research on regulation of pituitary hormones, extra-pituitary release of these hormones, distribution of their receptors and cell signaling pathways recruited upon receptor binding suggests that pituitary hormones can regulate mechanisms of nociceptive transmission in multiple orofacial pain conditions. Moreover, many pituitary hormones either regulate glands that produce gonadal hormones (GnH) or are regulated by GnH. This implies that pituitary hormones may be involved in sex-dependent mechanisms of orofacial pain and could help explain why certain orofacial pain conditions are more prevalent in women than men. Overall, regulation of nociception by pituitary hormones is a relatively new and emerging area of pain research. The aims of this review article are to: (1) present an overview of clinical conditions leading to orofacial pain that are associated with alterations of serum pituitary hormone levels; (2) discuss proposed mechanisms of how pituitary hormones could regulate nociceptive transmission; and (3) outline how pituitary hormones could regulate nociception in a sex-specific fashion. Pituitary hormones are routinely used for hormonal replacement therapy, while both receptor antagonists and agonists are used to manage certain pathological conditions related to hormonal imbalance. Administration of these hormones may also have a place in the treatment of pain, including orofacial pain. Hence, understanding the involvement of pituitary hormones in orofacial pain, especially sex-dependent aspects of such pain, is essential to both optimize current therapies as well as provide novel and sex-specific pharmacology for a diversity of associated conditions.
Project description:The aim of this review is to evaluate the developmental, functional, and morphological aspects of the craniofacial complex in patients with myotonic dystrophy type 1 (DM1), Facioscapulohumeral muscular dystrophy (FSHD), and Duchenne muscular dystrophy (DMD). The degree of disease onset and severity varied from patient to patient, and most parameters indicated a greater degree of deterioration in older patients. It was found that all the muscular dystrophies studied showed altered craniofacial morphology, with malocclusion as the most consistent clinical characteristic. Particularly DM1 patients, who are the most studied, showed significant vertical aberration and post-normal occlusion. DMD patients are reported mainly with altered dental arch dimensions which influence functional capacities. Data for FSHD patients are very limited, but facial asymmetry and muscular weakness appear to be the most prominent findings. Patients with muscular dystrophies present deviations in growth and development as well as in orofacial morphology. Increased prevalence of malocclusions, of both skeletal and dental origins, characterize patients with muscular dystrophies. Different dentofacial characteristics are reported among patients with different types of muscular dystrophies. Further research is needed to clarify the orofacial phenotypic expression of muscular dystrophies.
Project description:Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with primary chronic pain syndromes, such as fibromyalgia, migraine, and chronic low back pain. Although idiopathic orofacial pain (IOP) is classified as burning mouth syndrome or persistent idiopathic facial or dentoalveolar pain and as a primary chronic pain, the association between IOP and ADHD has not been investigated. This retrospective cohort study investigated the severity of ADHD symptoms measured using the ADHD scale and the effects of treatment using ADHD drugs and the dopamine system stabilizer aripiprazole. The participants were 25 consecutive patients with refractory IOP referred to a psychiatrist and diagnosed with coexisting ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-5. The ADHD scale scores were higher in patients with intractable IOP than those in the general population. Pharmacotherapy used in this study led to clinically significant improvements in pain, anxiety/depression, and pain catastrophizing. Intractable IOP and ADHD were shown to be associated. In the future, screening and pharmacotherapy for ADHD should be considered in the treatment of intractable IOP.
Project description:Facioscapulohumeral muscular dystrophy is the third most commonly found type of muscular dystrophy. The aim of this study was to correlate the D4Z4 repeat array fragment size to the orofacial muscle weakening exhibited in a group of patients with a genetically supported diagnosis of FSHD. Molecular genetic analysis was performed for 52 patients (27 female and 25 male) from a group that consisted of 36 patients with autosomal dominant pedigrees and 16 patients with either sporadic or unknown family status. The patients were tested with the southern blotting technique, using EcoRI/Avrll double digestion, and fragments were detected by a p13E-11 telomeric probe. Spearman's correlation was used to compare the fragment size with the degree of muscle weakening found in the forehead, periocular and perioral muscles. A positive non-significant correlation between the DNA fragment size and severity of muscle weakness was found for the forehead (r = 0.27; p = 0187), the periocular (r = 0.24; p = 0.232) and the left and right perioral (r = 0.29; p = 0.122), (r = 0.32; p = 0.085) muscles. Although FSHD patients exhibited a decrease in muscular activity related to the forehead, perioral, and periocular muscles the genotype-phenotype associations confirmed a weak to moderate non-significant correlation between repeat size and the severity of muscle weakness. Orofacial muscle weakening and its association with a D4Z4 contraction alone may not have the significance to serve as a prognostic biomarker, due to the weak to moderate association. Further studies with larger sample sizes are needed to determine the degree of genetic involvement in the facial growth in FSHD patients.
Project description:Duchenne muscular dystrophy is an X-linked, recessive muscular dystrophy in which the absence of the dystrophin protein leads to fibrosis, inflammation and oxidative stress, resulting in loss of muscle tissue. Drug repurposing, i.e. using drugs already approved for other disorders, is attractive as it decreases development time. Recent studies suggested that simvastatin, a cholesterol lowering drug used for cardiovascular diseases, has beneficial effects on several parameters in mdx mice. To validate properly the effectiveness of simvastatin, two independent labs tested the effects of 12-week simvastatin treatment in either young (starting at 4 weeks of age) or adult (starting at 12 weeks of age) mdx mice. In neither study were benefits of simvastatin treatment observed on muscle function, histology or expression of genes involved in fibrosis, regeneration, oxidative stress and autophagy. Unexpectedly, although the treatment protocol was similar, simvastatin plasma levels were found to be much lower than observed in a previous study. In conclusion, in two laboratories, simvastatin did not ameliorate disease pathology in mdx mice, which could either be due to the ineffectiveness of simvastatin itself or due to the low simvastatin plasma levels following oral administration via the food.
Project description:BackgroundThe purpose of this study was to evaluate the clinical outcomes of treatment of non-odontogenic atypical orofacial pain using botulinum toxin-A.MethodsThis study involved seven patients (seven females, mean age 65.1 years) who had non-odontogenic orofacial pain (neuropathic pain and atypical orofacial pain) and visited the Seoul National University Bundang Hospital between 2015 and 2017. All medication therapies were preceded by botulinum toxin-A injections, followed by injections in the insignificant effects of medication therapies. Five of the seven patients received intraoral injections in the gingival vestibule or mucosa, while the remaining two received extraoral injections in the masseter and temporal muscle areas.ResultsIn five of the seven patients, pain after botulinum toxin-A injection was significantly reduced. Most of the patients who underwent surgery for dental implantation or facial nerve reconstruction recovered after injections. However, the pain did not disappear in two patients who reported experiencing persistent pain without any cause.ConclusionsThe use of botulinum toxin-A for the treatment of non-odontogenic neuropathic orofacial pain is clinically useful. It is more effective to administer botulinum toxin-A in combination with other medications and physical therapy to improve pain.