Sidharth Tyagi
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View article: Selective targeting of voltage-gated sodium channels to achieve analgesia: current status and future directions
Selective targeting of voltage-gated sodium channels to achieve analgesia: current status and future directions Open
Voltage-gated sodium channels (Na v ) play a fundamental role in generating action potentials in excitable cells including nociceptors. Certain Na v subtypes are enriched in nociceptors, and human genetic data link them to pain disorders m…
View article: Effects of stapes surgery prosthesis type on hearing outcome, post-operative dizziness and benzodiazepine use
Effects of stapes surgery prosthesis type on hearing outcome, post-operative dizziness and benzodiazepine use Open
Objective Investigate the impact of surgical method on hearing outcomes and complication rates after otosclerosis surgery. Methods Records of patients more than 18 years old who underwent otosclerosis surgery were reviewed to identify pros…
View article: Targeted ubiquitination of Na<sub>V</sub>1.8 reduces sensory neuronal excitability
Targeted ubiquitination of Na<sub>V</sub>1.8 reduces sensory neuronal excitability Open
Chronic pain and addiction are a significant global health challenge. Voltage-gated sodium channel Na V 1.8, a pivotal driver of pain signaling, is a clinically validated target for the development of novel, non-addictive pain therapeutics…
View article: Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids
Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids Open
Pain impacts billions of people worldwide, but treatment options are limited and have a spectrum of adverse effects. The search for safe and nonaddictive pain treatments has led to a focus on key mediators of nociceptor excitability. Volta…
View article: TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons
TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons Open
Collectively, our findings suggest that proexcitatory mutations of TRPM8, in the context of axonal injury within the cornea, can produce trigeminal ganglion neuron hyperexcitability that contributes to persistent postoperative ocular pain.…
View article: Financial Compensation of Academic Otolaryngologists in the United States: Trends and Distribution
Financial Compensation of Academic Otolaryngologists in the United States: Trends and Distribution Open
Objectives The aim of this study was to assess recent trends in financial compensation in the field of academic otolaryngology, and distribution based on rank, sex, race/ethnicity, and geographical regions in academic medical centers. Meth…
View article: Impacts of resident physician unionization on house staff compensation
Impacts of resident physician unionization on house staff compensation Open
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 st…
View article: Real-time imaging of axonal membrane protein life cycles
Real-time imaging of axonal membrane protein life cycles Open
The construction of neuronal membranes is a dynamic process involving the biogenesis, vesicular packaging, transport, insertion and recycling of membrane proteins. Optical imaging is well suited for the study of protein spatial organizatio…
View article: Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α
Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α Open
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 (NaV) channels. We show here that…
View article: Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes
Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes Open
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 re…
View article: Cost-effectiveness of hypothetical miRNA biomarker testing for post-treatment surveillance of HPV-negative OPSCC
Cost-effectiveness of hypothetical miRNA biomarker testing for post-treatment surveillance of HPV-negative OPSCC Open
Objective: To determine the theoretical cost-effectiveness of a miRNA-biomarker test for HPV– oropharyngeal squamous cell carcinoma surveillance compared to current National Comprehensive Cancer Network (NCCN) guidelines. Study design: Cos…
View article: An observational study on spectrum of complications in gallstone disease in Western Maharashtra
An observational study on spectrum of complications in gallstone disease in Western Maharashtra Open
Gallbladder calculus prevalence exhibits significant regional disparities, affecting public health. This study aimed to assess the incidence of complications in diagnosed cases of gallbladder stones using a prospective observational approa…
View article: Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs
Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs Open
Non-addictive treatment of chronic pain represents a major unmet clinical need. Peripheral voltage-gated sodium (Na V ) channels are an attractive target for pain therapy because they initiate and propagate action potentials in primary aff…
View article: Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity Open
Inflammation causes pain by shifting the balance of ionic currents in nociceptors toward depolarization, leading to hyperexcitability. The ensemble of ion channels within the plasma membrane is regulated by processes including biogenesis, …
View article: Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8
Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8 Open
Patients treated with paclitaxel (PTX) or other antineoplastic agents can experience chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect characterized by numbness and pain. PTX interferes with microtubule-based tr…
View article: High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons
High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons Open
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…
View article: The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation
The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation Open
Neuronal function relies on the maintenance of appropriate levels of various ion channels at the cell membrane, which is accomplished by balancing secretory, degradative, and recycling pathways. Neuronal function further depends on membran…
View article: Depolarizing Na<sub>V</sub> and Hyperpolarizing K<sub>V</sub> Channels Are Co-Trafficked in Sensory Neurons
Depolarizing Na<sub>V</sub> and Hyperpolarizing K<sub>V</sub> Channels Are Co-Trafficked in Sensory Neurons Open
Neuronal excitability relies on coordinated action of functionally distinction channels. Voltage-gated sodium (NaV) and potassium (KV) channels have distinct but complementary roles in firing action potentials: NaV channels provide depolar…
View article: Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies
Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies Open
The P/Q-type CaV2.1 channel regulates neurotransmitter release at neuromuscular junctions (NMJ) and many central synapses. CACNA1A encodes the pore-containing α1A subunit of CaV2.1 channels. In humans, de novo CACNA1A mutations result in a…