TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons.

Background And Objectives: Despite extensive efforts, the mechanisms underlying pain after axonal injury remain incompletely understood. Pain following corneal refractive surgery offers a valuable human model for investigating trigeminal axonal injury because laser-assisted in situ keratomileusis (LASIK) severs axons of trigeminal ganglion neurons innervating the cornea. While the majority of patients are pain-free shortly after surgery, a minority endure persistent postoperative ocular pain.

Impacts of resident physician unionization on house staff compensation.

Background: Physicians-in-training in the United States work long hours for relatively low wages. In response to increased economic burden, the popularity of unionization in residency training programs has increased dramatically. In this study, we conducted a cross-sectional investigation of the association between unionization status and Internal Medicine PGY-1 compensation and benefits.

The evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic.

The patch-clamp technique has been the gold standard for analysis of excitable cells. Since its development in the 1980s it has contributed immensely to our understanding of neurons, muscle cells, and cardiomyocytes, and the ion channels and receptors that reside within them. This technique, predicated on Ohm's law, enables precise measurements of macroscopic excitability patterns, and ionic and gating conductances that can be assessed even down to the single channel level.

Molecular Pharmacology of Selective Na1.6 and Dual Na1.6/Na1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo.

Voltage-gated sodium channel (Na) inhibitors are used to treat neurological disorders of hyperexcitability such as epilepsy. These drugs act by attenuating neuronal action potential firing to reduce excitability in the brain. However, all currently available Na-targeting antiseizure medications nonselectively inhibit the brain channels Na1.

Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol.

Cannabinol (CBN), an incompletely understood metabolite for ∆9-tetrahydrocannabinol, has been suggested as an analgesic. CBN interacts with endocannabinoid (CB) receptors, but is also reported to interact with non-CB targets, including various ion channels. We assessed CBN effects on voltage-dependent sodium (Nav) channels expressed heterologously and in native dorsal root ganglion (DRG) neurons.

Compartment-specific regulation of Na1.7 in sensory neurons after acute exposure to TNF-α.

Tumor necrosis factor α (TNF-α) is a major pro-inflammatory cytokine, important in many diseases, that sensitizes nociceptors through its action on a variety of ion channels, including voltage-gated sodium (Na) channels. We show here that TNF-α acutely upregulates sensory neuron excitability and current density of threshold channel Na1.7.

Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes.

Sexual dimorphism has been reported in multiple pre-clinical and clinical studies on pain. Previous investigations have suggested that in at least some states, rodent dorsal root ganglion (DRG) neurons display differential sex-dependent regulation and expression patterns of various proteins involved in the pain pathway. Our goal in this study was to determine whether sexual dimorphism in the biophysical properties of voltage-gated sodium (Nav) currents contributes to these observations in rodents.

High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons.

The patch-clamp technique is the gold-standard methodology for analysis of excitable cells. However, throughput of manual patch-clamp is slow, and high-throughput robotic patch-clamp, while helpful for applications like drug screening, has been primarily used to study channels and receptors expressed in heterologous systems. We introduce an approach for automated high-throughput patch-clamping that enhances analysis of excitable cells at the channel and cellular levels.

Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons.

Despite extensive study, the mechanisms underlying pain after axonal injury remain incompletely understood. Pain after corneal refractive surgery provides a model, in humans, of the effect of injury to trigeminal afferent nerves. Axons of trigeminal ganglion neurons that innervate the cornea are transected by laser-assisted in situ keratomileusis (LASIK).

Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol.

Phytocannabinoids, found in the plant, , are an important class of natural compounds with physiological effects. These compounds can be generally divided into two classes: psychoactive and non-psychoactive. Those which do not impart psychoactivity are assumed to predominantly function endocannabinoid receptor (CB) -independent pathways and molecular targets, including other receptors and ion channels.

Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study.

Gramicidin is a monomeric protein that is thought to non-selectively conduct cationic currents and water. Linear gramicidin is considered an antibiotic. This function is considered to be mediated by the formation of pores within the lipid membrane, thereby killing bacterial cells.

An Adaptive Element-Level Impedance-Matched ASIC With Improved Acoustic Reflectivity for Medical Ultrasound Imaging.

This paper presents an active impedance matching scheme that tries to optimize electrical power transfer and acoustic reflectivity in ultrasound transducers. Leveraging negative capacitance-based impedance matching would potentially improve the bandwidth and electrical power transfer while minimizing acoustic reflection of transducer elements and improve uniformity while reducing acoustic crosstalk of transducer arrays. A 16-element transceiver front-end is designed which employs an element-level active capacitive impedance cancellation scheme using an element-level negative impedance converter.

Late sodium current: incomplete inactivation triggers seizures, myotonias, arrhythmias, and pain syndromes.

Acquired and inherited dysfunction in voltage-gated sodium channels underlies a wide range of diseases. In addition to defects in trafficking and expression, sodium channelopathies are caused by dysfunction in one or several gating properties, for instance activation or inactivation. Disruption of channel inactivation leads to increased late sodium current, which is a common defect in seizure disorders, cardiac arrhythmias skeletal muscle myotonia and pain.

Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability.

Background And Purpose: Cannabigerol (CBG), a non-psychotropic phytocannabinoid and a precursor of ∆ -tetrahydrocannabinol and cannabidiol, has been suggested to act as an analgesic. A previous study reported that CBG (10 μM) blocks voltage-gated sodium (Na ) currents in CNS neurons, although the underlying mechanism is not well understood. Genetic and functional studies have validated Na 1.

Design and Preliminary Evaluation of a Tongue-Operated Exoskeleton System for Upper Limb Rehabilitation.

Stroke is a devastating condition that may cause upper limb paralysis. Robotic rehabilitation with self-initiated and assisted movements is a promising technology that could help restore upper limb function. Previous studies have established that the tongue motion can be used to communicate human intent and control a rehabilitation robot/assistive device.

Cannabidiol and Sodium Channel Pharmacology: General Overview, Mechanism, and Clinical Implications.

Voltage-gated sodium (Nav) channels initiate action potentials in excitable tissues. Altering these channels' function can lead to many pathophysiological conditions. Nav channels are composed of several functional and structural domains that could be targeted pharmacologically as potential therapeutic means against various neurological conditions.

Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity.

Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.

Biophysical Characterization of a Novel Mutation Associated With an Atypical Phenotype of Atrial and Ventricular Arrhythmias and Sudden Death.

Background: Sudden cardiac death (SCD) is an unexpected death that occurs within an hour of the onset of symptoms. Hereditary primary electrical disorders account for up to 1/3 of all SCD cases in younger individuals and include conditions such as catecholaminergic polymorphic ventricular tachycardia (CPVT). These disorders are caused by mutations in the genes encoding cardiac ion channels, hence they are known as cardiac channelopathies.

A Trimodal Wireless Implantable Neural Interface System-on-Chip.

A wireless and battery-less trimodal neural interface system-on-chip (SoC), capable of 16-ch neural recording, 8-ch electrical stimulation, and 16-ch optical stimulation, all integrated on a 5 ×  3 mm chip fabricated in 0.35-μm standard CMOS process. The trimodal SoC is designed to be inductively powered and communicated.

Cannabidiol interactions with voltage-gated sodium channels.

Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels.

A Power-Efficient Bridge Readout Circuit for Implantable, Wearable, and IoT Applications.

A power-efficient bridge-to-digital sensing interface is proposed, which also offers immunity against power supply noise. The interface utilizes duty-cycling to reduce the static power consumption of resistive bridge sensors, which are commonly used in implantable, wearable, and internet of things (IoT) applications, such as intracranial pressure (ICP) sensing and blood pressure (BP) monitoring. The proposed interface uses a revised version of the pseudo-pseudo differential (PPD) topology with the ping-pong technique to reduce the complexity of traditional fully-differential counterparts.

A mm-Sized Free-Floating Wireless Implantable Opto-Electro Stimulation Device.

Towards a distributed neural interface, consisting of multiple miniaturized implants, for interfacing with large-scale neuronal ensembles over large brain areas, this paper presents a mm-sized free-floating wirelessly-powered implantable opto-electro stimulation (FF-WIOS2) device equipped with 16-ch optical and 4-ch electrical stimulation for reconfigurable neuromodulation. The FF-WIOS2 is wirelessly powered and controlled through a 3-coil inductive link at 60 MHz. The FF-WIOS2 receives stimulation parameters via on-off keying (OOK) while sending its rectified voltage information to an external headstage for closed-loop power control (CLPC) via load-shift-keying (LSK).

Highly Integrated Guidewire Ultrasound Imaging System-on-a-Chip.

In this article, we present a highly integrated guidewire ultrasound (US) imaging system-on-a-chip (GUISoC) for vascular imaging. The SoC consists of a 16-channel US transmitter (Tx) and receiver (Rx) electronics, on-chip power management IC (PMIC), and quadrature sampler. Using a synthetic aperture imaging algorithm, a Tx/Rx pair, connected to capacitive micromachined ultrasound transducers (CMUTs), can be activated at any time.