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

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

Enhanced <i>I_NaP</i> in A-type neurons of the compressed DRG.

<p>(A) Traces of <i>I_NaP</i> in A-type neurons from control (normal; grey line) and compressed (CCD, solid line) DRGs (bottom) as induced by increasing applied voltage (top). (B) Bar graph showing that the average peak <i>I_NaP</i> is significantly greater in neurons recorded from compressed DRGs (CCD; n = 31) compared to the average peak value from control group recordings (normal; n = 26; *P<0.05). (C) Bar graph showing that average peak <i>I_NaP</i> current density is significantly greater in compressed DRG neurons (n = 31) compared to the average peak value from control group recordings (n = 26; *P<0.05). (D) Steady state activation curves for <i>I_NaP</i> conductance with respect to voltage in control and compressed DRG neurons as fit with a Boltzmann distribution equation. The differences are not statistically significant. (E) Traces of <i>I_NaP</i> in a compressed DRG neuron in the absence (control, solid line) and presence (DMSO, grey line) of 0.1% DMSO (bottom) as induced by increasing applied voltage (top). (F) Bar graph showing that average peak <i>I_NaP</i> in compressed DRG neurons (n = 7) in the presence of 0.1% DMSO is not significantly different from the average peak <i>I_NaP</i> in the absence of DMSO (control, filled; n = 7; P>0.05).</p

Effects of riluzole on <i>I_NaP</i> and <i>I_NaT</i> in A-type neurons of the compressed DRG.

<p>(A) Traces of <i>I_NaP</i> (bottom) induced by increasing applied voltage (top) in a compressed DRG neuron in the absence (control) and presence of riluzole (2, 10, 50 µM). (B) Dose-inhibition curve showing effect of locally applied riluzole on <i>I_NaP</i> in compressed DRG neurons (n = 5; IC₅₀ = 4.3 µM). (C) <i>I_NaT</i> traces in a DRG neuron evoked by applied depolarization (−20 mV) under control conditions and in the presence of riluzole (10, 200, 500 µM). (D) Bar graph showing that average peak <i>I_NaT</i> current density (pA/pF) in the presence of riluzole (10, 200, 500 µM) is significantly decreased in neurons recorded from compressed DRGs (*P<0.05, **P<0.01).</p

Mechanical allodynia in CCD rats.

<p>(A) Time course of changes in the withdrawl threshold of the ipsilateral hindpaw for control (n = 6, open circles) and CCD (n = 4, closed circles) rats. The mechanical threshold for withdrawl of the ipsilateral hindpaw was significantly lower in the chronically compressed rats (* P<0.05 or **P<0.01 compared with the average for the ipsilateral hindpaw of the control group). (B) Average ipsilateral and contralateral paw withdrawl thresholds for the control and CCD groups on the postoperative 5 days.</p