Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities.

Objectives: Rats are commonly used for translational pain and spinal cord stimulation (SCS) research. Although many SCS parameters are configured identically between rats and humans, stimulation amplitudes in rats are often programmed relative to visual motor threshold (vMT). Alternatively, amplitudes may be programmed relative to evoked compound action potential (ECAP) thresholds (ECAPTs), a sensed measure of neural activation.

Modulation of Glia-Mediated Processes by Spinal Cord Stimulation in Animal Models of Neuropathic Pain.

Glial cells play an essential role in maintaining the proper functioning of the nervous system. They are more abundant than neurons in most neural tissues and provide metabolic and catabolic regulation, maintaining the homeostatic balance at the synapse. Chronic pain is generated and sustained by the disruption of glia-mediated processes in the central nervous system resulting in unbalanced neuron-glial interactions.

Modulation of microglial activation states by spinal cord stimulation in an animal model of neuropathic pain: Comparing high rate, low rate, and differential target multiplexed programming.

While numerous studies and patient experiences have demonstrated the efficacy of spinal cord stimulation as a treatment for chronic neuropathic pain, the exact mechanism underlying this therapy is still uncertain. Recent studies highlighting the importance of microglial cells in chronic pain and characterizing microglial activation transcriptomes have created a focus on microglia in pain research. Our group has investigated the modulation of gene expression in neurons and glial cells after spinal cord stimulation (SCS), specifically focusing on transcriptomic changes induced by varying SCS stimulation parameters.

Spinal cord stimulation using differential target multiplexed programming modulates neural cell-specific transcriptomes in an animal model of neuropathic pain.

Spinal cord stimulation is a proven effective therapy for treating chronic neuropathic pain. Previous work in our laboratory demonstrated that spinal cord stimulation based on a differential target multiplexed programming approach provided significant relief of pain-like behavior in rodents subjected to the spared nerve injury model of neuropathic pain. The relief was significantly better than obtained using high rate and low rate programming.

Muscle insulin resistance in type 1 diabetes with coronary artery disease.

Aims/hypothesis: The risk for coronary artery disease (CAD) is substantially increased in type 1 diabetes and it has been postulated that insulin resistance may contribute to this risk. The current study measured insulin resistance in type 1 diabetes with vs without CAD and with a focus upon skeletal muscle, to test the hypothesis that insulin resistance is more severe in participants who have type 1 diabetes and CAD. Additionally, in type 1 diabetes, we examined the hypothesis that insulin resistance is more severe in soleus (an oxidative type muscle) vs tibialis anterior (a more glycolytic type of muscle).

Redox signaling modulates Rho activity and tissue contractility in the spermatheca.

Actomyosin-based contractility in smooth muscle and nonmuscle cells is regulated by signaling through the small GTPase Rho and by calcium-activated pathways. We use the myoepithelial cells of the spermatheca to study the mechanisms of coordinated myosin activation in vivo. Here, we show that redox signaling modulates RHO-1/Rho activity in this contractile tissue.

Modulation of neuroglial interactions using differential target multiplexed spinal cord stimulation in an animal model of neuropathic pain.

The development and maintenance of chronic neuropathic pain involves distorted neuroglial interactions, which result in prolonged perturbations of immune and inflammatory response, as well as disrupted synapses and cellular interactions. Spinal cord stimulation (SCS) has proven effective and safe for more than 40 years, but comprehensive understanding of its mode of action remains elusive. Previous work in our laboratory provided evidence that conventional SCS parameters modulate biological processes associated with neuropathic pain in animals.

Proteomic Modulation in the Dorsal Spinal Cord Following Spinal Cord Stimulation Therapy in an In Vivo Neuropathic Pain Model.

Objectives: Spinal cord stimulation (SCS) provides relief for patients suffering from chronic neuropathic pain although its mechanism may not be as dependent on electrical interference as classically considered. Recent evidence has been growing regarding molecular changes that are induced by SCS as being a key player in reversing the pain process. Here, we observed the effect of SCS on altering protein expression in spinal cord tissue using a proteomic analysis approach.

Electrical Stimulation of C6 Glia-Precursor Cells In Vitro Differentially Modulates Gene Expression Related to Chronic Pain Pathways.

Glial cells comprise the majority of cells in the central nervous system and exhibit diverse functions including the development of persistent neuropathic pain. While earlier theories have proposed that the applied electric field specifically affects neurons, it has been demonstrated that electrical stimulation (ES) of neural tissue modulates gene expression of the glial cells. This study examines the effect of ES on the expression of eight genes related to oxidative stress and neuroprotection in cultured rodent glioma cells.

Effects of Phase Polarity and Charge Balance Spinal Cord Stimulation on Behavior and Gene Expression in a Rat Model of Neuropathic Pain.

Objective: To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action.

Materials And Methods: Rats were implanted with a four-contact cylindrical mini-lead and randomly assigned to two control (no-pain and pain model) and five test groups featuring monophasic, as well as charge-unbalanced and charge-balanced biphasic SCS waveforms.

The myosin light-chain kinase MLCK-1 relocalizes during Caenorhabditis elegans ovulation to promote actomyosin bundle assembly and drive contraction.

We identify the Caenorhabditis elegans myosin light-chain kinase, MLCK-1, required for contraction of spermathecae. During contraction, MLCK-1 moves from the apical cell boundaries to the basal actomyosin bundles, where it stabilizes myosin downstream of calcium signaling. MLCK and ROCK act in distinct subsets of cells to coordinate the timing of contraction.

Comparisons of Lesion Volumes and Shapes Produced by a Radiofrequency System with a Cooled, a Protruding, or a Monopolar Probe.

Background: Radiofrequency (RF) ablation for denervation has been utilized for decades in chronic pain management. This relies on the proper targeting of the affected nerve which may be obtained by creating an ablation lesion with a shape and volume that optimizes targeting. Various systems designed to improve lesion size are available.

BioSIMP: Using Software Testing Techniques for Sampling and Inference in Biological Organisms.

Years of research in software engineering has given us novel ways to reason about, test, and predict the behavior of complex software systems that contain hundreds of thousands of lines of code. Many of these techniques have been inspired by nature such as genetic algorithms, swarm intelligence, and ant colony optimization. In this paper we reverse the direction and present BioSIMP, a process that models and predicts the behavior of biological organisms to aid in the emerging field of systems biology.

Epidural Spinal Stimulation to Improve Bladder, Bowel, and Sexual Function in Individuals With Spinal Cord Injuries: A Framework for Clinical Research.

While some recent studies that apply epidural spinal cord stimulation (SCS) have demonstrated a breakthrough in improvement of the health and quality of the life of persons with spinal cord injury (SCI), the numbers of people who have received SCS are small. This is in sharp contrast to the thousands of persons worldwide living with SCI who have no practical recourse or hope of recovery of lost functions. Thus, the vision is to understand the full potential of this new intervention and to determine if it is safe and effective in a larger cohort, and if it is scalable so that it can be made available to all those who might benefit.

Changes in Dorsal Root Ganglion Gene Expression in Response to Spinal Cord Stimulation.

Background And Objectives: Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy.

Chemotherapy Significantly Improves Survival for Patients with T1c-T2N0M0 Medullary Breast Cancer: 3739 Cases From the National Cancer Data Base.

Background: Medullary breast cancer (MBC) is a rare tumor associated with a better prognosis compared with other breast cancers. The role of adjuvant chemotherapy has not been extensively studied.

Methods: Female patients with invasive MBC reported to the National Cancer Data Base from 2004 to 2012 were analyzed.

Spinal Cord Stimulation Modulates Gene Expression in the Spinal Cord of an Animal Model of Peripheral Nerve Injury.

Background And Objectives: Previously, we found that application of pulsed radiofrequency to a peripheral nerve injury induces changes in key genes regulating nociception concurrent with alleviation of paw sensitivity in an animal model. In the current study, we evaluated such genes after applying spinal cord stimulation (SCS) therapy.

Methods: Male Sprague-Dawley rats (n = 6 per group) were randomized into test and control groups.

Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base.

Backgrounds And Objectives: Medullary breast carcinoma (MBC) is a subtype with a more favorable prognosis. Tumors with some, but not all, characteristics of MBC are classified as atypical medullary carcinoma of the breast (AMCB).

Methods: Patients with invasive MBC and AMCB reported to the National Cancer Data Base (NCDB) from 2004 to 2013 were compared for tumor characteristics and overall survival, using infiltrating ductal carcinoma (IDC) as a reference.

Genomics of the Effect of Spinal Cord Stimulation on an Animal Model of Neuropathic Pain.

Background: Few studies have evaluated single-gene changes modulated by spinal cord stimulation (SCS), providing a narrow understanding of molecular changes. Genomics allows for a robust analysis of holistic gene changes in response to stimulation.

Methods: Rats were randomized into six groups to determine the effect of continuous SCS in uninjured and spared-nerve injury (SNI) animals.