Blockade of Persistent Sodium Currents Contributes to the Riluzole-Induced Inhibition of Spontaneous Activity and Oscillations in Injured DRG Neurons

In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (INaP). The INaP is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of INaP in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the INaP, also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the INaP was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the INaP without affecting the transient sodium current (INaT). Taken together, these results demonstrate for the first time that the INaP blocker riluzole selectively inhibits INaP and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the INaP of DRG neurons is a potential target for treating neuropathic pain at the peripheral level

Case report: Successful treatment of non-bullous lichen planus pemphigoides with dupilumab

Lichen planus pemphigoides (LPP) is a rare autoimmune bullous disease, characterized by the coexistence of lichen planus and subepidermal bullae. However, the minority of LPP patients present with papules rather than vesicles or blisters, which is defined as non-bullous LPP. The diagnosis of LPP relies on manifestations, histopathology, serological assay, and direct immunofluorescence of linear disposition of IgG and/or C3 at the basement membrane zone. Up to now, no standard therapeutic strategies have been proposed for the treatment of LPP. Herein, we describe an uncommon non-bullous LPP patient with widespread papules and erythema, probably induced by vaccination. During hospitalization, he had a poor response to the conventional treatment of topical and systemic corticosteroids, and his condition was finally alleviated by the addition of dupilumab. For LPP patients with a traditional medication failure, or who were not suitable for a higher dose of corticosteroids, a combination with dupilumab could be an alternative option

Identification of Glycine Receptor α3 as a Colchicine-Binding Protein

Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyRα3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyRα3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyRα3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyRα3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations

Presynaptically Localized Cyclic GMP-Dependent Protein Kinase 1 Is a Key Determinant of Spinal Synaptic Potentiation and Pain Hypersensitivity

Electrophysiological and behavioral experiments in mice reveal that a cGMP-dependent kinase amplifies neurotransmitter release from peripheral pain sensors, potentiates spinal synapses, and leads to exaggerated pain

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics

Safety management of medical neurobiology laboratory

More and more attention has been paid to the safety of laboratory in colleges. The laboratory biosafety management system following the principle of human safety is the pre-condition of a routine laboratory operation.Under the national regulation and technical guidance about laboratory safety management, this paper reviewed the potential risk factors in the neurobiology laboratory, and put forward feasible solutions. Through safety training, the establishment of safety management system,standardized procedurs and extensive supervision system, the medical students in the neurobiology laboratory are constrained in terms of ideology, system and management norms, in order to improve the students'awareness, cultivate training of GOP techonology,so to ensure the safety of medical students in the neurobiology laboratory

Manganese-superoxide dismutase (MnSOD) rescues redox balance and mucosal barrier function in midgut of hybrid fish (Carassius cuvieri ♀ × Carassius auratus red var ♂) infected with Aeromonas hydrophila and Edwardsiella tarda

MnSOD is a ubiquitous metalloenzyme that constitutes the first line of antioxidant defense against oxidative stress. In this study, full length sequence of MnSOD was identified from hybrid crucian carp (WR, Carassius cuvieri ♀ × Carassius auratus red var ♂). Tissue-specific analysis revealed that the highest expression of WR-MnSOD was detected in kidney. Aeromonas hydrophila challenge could dramatically enhance WR-MnSOD mRNA expression in tissues. In vivo administration of purified WR-MnSOD peptide could maintain gut mucosal barrier function, rescue redox balance as well as decrease apoptotic cell death in midgut upon bacterial infection, suggesting that WR-MnSOD is playing a crucial role in gut mucosal barrier function and could be used as feed additive to improve gut immunity in fish

Origin of hypoglycemic benefits of probiotic-fermented carrot pulp

It has been found that probiotic-fermented carrot pulp has a beneficial effect in reducing blood glucose, more so than unfermented pulp. This paper explores the reason for this by looking at fermentation-induced changes in nutritional components and hypoglycemic effects of its polysaccharides. Micronutrient content showed minor changes, except for titratable acidity. Fat and protein decreased, while total carbohydrates increased. These polysaccharides are pectinic, and the number of total polysaccharides rose after fermentation. Scanning electron microscopy showed that the morphology changed from filamentous solid to spiral. The molecular weight of water-soluble polysaccharide (WSP) diminished after fermentation, while those of acid- and alkali-soluble polysaccharides increased. WSP had stronger hydroxyl radical scavenging activity in vitro, and WSP from probiotic-fermented carrot pulps showed better hypoglycemic effects than WSP from non-fermented carrot pulps in animal experiments. Thus, the fermentation-induced improvement in diabetes control from fermented carrot pulp probably arises from its WSP