The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain. In addition, focal application of GABA receptor antagonists to sensory ganglia triggered or exacerbated peripherally induced nociception. We also demonstrated that chemogenetic or optogenetic depolarization of GABAergic dorsal root ganglion neurons in vivo reduced acute and chronic peripherally induced nociception. Mechanistically, GABA depolarized the majority of sensory neuron somata, yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at nociceptive fiber T-junctions. Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a potential target for therapeutic intervention.
Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information in mice undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support “gating” of pain information by DRGs and suggest new therapeutic approaches for pain relief.
Recent studies suggested that Eurycoma longifolia, a herbal plant, may have the potential to treat osteoporosis in elderly male. This study aimed to determine the effects of Eurycoma longifolia supplementation on the trabecular bone microarchitecture of orchidectomised rats (androgen-deficient osteoporosis model). Forty-eight-aged (10–12 months old) Sprague Dawley rats were divided into six groups of sham-operated (SHAM), orchidectomised control (ORX), orchidectomised + 7 mg/rat testosterone enanthate (TEN) and orchidectomised + Eurycoma longifolia 30 mg/kg (EL30), orchidectomised + Eurycoma longifolia 60 mg/kg (EL60), orchidectomised + Eurycoma longifolia 90 mg/kg (EL90). Rats were euthanized following six weeks of treatment. The left femora were used to measure the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly decreased connectivity density, trabecular bone volume, and trabecular number compared to the SHAM group. Testosterone replacement reversed all the orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg rat worsened the trabecular bone connectivity density and trabecular separation parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume. High dose of EL (90 mg/kg) may have potential in preserving the bone microarchitecture of orchidectomised rats, but lower doses may further worsen the osteoporotic changes.
The Bio-ecological Drainage System, or BIOECODS, is an urban drainage system located at the Engineering Campus, Universiti Sains Malaysia. It consists of a constructed wetland as a part of the urban drainage system to carry storm water in a closed system. In this closed system, the constructed wetland was designed particularly for further treatment of storm water. For the purpose of studying the water balance of the constructed wetland, data collection was carried out for two years (2007 and 2009). The results show that the constructed wetland has a consistent volume of water storage compared to the outflow for both years with correlation coefficients (R(2)) of 0.99 in 2007 and 0.86 in 2009.
Background: The prevalence of excessive daytime sleepiness (EDS) is high among college and university students. EDS has been associated with poor concentration and forgetfulness that affect poor academic performance. Objective: This study aimed to evaluate the effect of EDS on academic performance among undergraduate dental students at the School of Dental Sciences in Universiti Sains Malaysia. Materials and Methods: A cross-sectional study involving 198 students of year two through year five were selected. Subjects were asked to complete a guided questionnaire which consists of socio-demographic profiles and Epworth Sleepiness Scale (ESS). Data were analyzed and presented as percentages of occurrence. Chi-square test and multiple regression analysis were performed to assess the association between ESS score and end of year examination results as a measure of students’ academic performance as well as other potential confounders—gender, body mass index (BMI) and ethnicity. Statistical significance was set at p<0.05. Results: The prevalence of EDS was 45% with students having mild, moderate and severe sleepiness were 38.4%, 5.5% and 1.5%, respectively. EDS was more common in males (51.9%) than females (43.2%). There was no significant association between ESS score and end of year results for each year (p>0.05). Similarly, BMI, gender and ethnicity also were not significantly associated with sleepiness. Conclusion: The high prevalence of EDS among dental students is a call for concern as it may affect their clinical practice and their mental and health wellbeing.
The prevalence of dentin hypersensitivity (DH) is increasing around the world. At least one in 10 individuals in the general population has been diagnosed with DH. It is a diagnosis that has significant negative effects on a person's oral health-related quality of life. This condition, which is characterized by sharp, short tooth pain in response to thermal, chemical, tactile, and evaporative stimuli, is more commonly seen in adults. DH has a tremendous impact on the social and financial aspects of patients and society at large. It is essential to recognize the factors that can contribute to a successful treatment outcome to guarantee the overall well-being of DH patients.The aim of this narrative review was to highlight strategies that can lead to successful DH treatment outcomes, along with current updates on DH mechanisms, treatment options, and the latest management approaches. A positive treatment outcome for DH requires a concerted effort from both the patient and the dental practitioner. Highly motivated patients and dental practitioners with sound knowledge of DH diagnosis and available treatment options will ensure successful long-term improvement of DH symptoms.
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