Transcriptomic and histological characterization of telocytes in the human dorsal root ganglion.

Telocytes are interstitial cells with long processes that cover distances in tissues and likely coordinate interacts with other cell types. Though present in central and peripheral neuronal tissues, their role remains unclear. Dorsal root ganglia (DRG) house pseudounipolar afferent neurons responsible for signals such as temperature, proprioception and nociception.

Ultrastructure of dorsal root ganglia.

Dorsal root ganglia (DRG) contains thousands of sensory neurons that transmit information about our external and internal environment to the central nervous system. This includes signals related to proprioception, temperature, and nociception. Our understanding of DRG has increased tremendously over the last 50 years and has established the DRG as an active participant in peripheral processes.

Clodronate Treatment Prevents Vaginal Hypersensitivity in a Mouse Model of Vestibulodynia.

Introduction: Improved understanding of vestibulodynia pathophysiology is required to develop appropriately targeted treatments. Established features include vulvovaginal hyperinnervation, increased nociceptive signalling and hypersensitivity. Emerging evidence indicates macrophage-neuron signalling contributes to chronic pain pathophysiology.

Neuroanatomical relationship between and the brachial plexus.

Background: This study examined the stratified anatomy of the traditional acupuncture point and the neuroanatomical relationship between and the brachial plexus, and investigated neural pathways that could be affected by acupuncture stimulation at .

Methods: Twelve dissected specimens were used to study the pathway of an acupuncture needle inserted at . The stratified anatomy and the neuroanatomical relationship between and the brachial plexus were studied.

Immortalized Dorsal Root Ganglion Neuron Cell Lines.

Pain is one of the most significant causes of suffering and disability world-wide, and arguably the most burdensome global health challenge. The growing number of patients suffering from chronic pain conditions such as fibromyalgia, complex regional pain syndrome, migraine and irritable bowel syndrome, not only reflect the complexity and heterogeneity of pain types, but also our lack of understanding of the underlying mechanisms. Sensory neurons within the dorsal root ganglia (DRG) have emerged as viable targets for effective chronic pain therapy.

Emerging Evidence of Macrophage Contribution to Hyperinnervation and Nociceptor Sensitization in Vulvodynia.

Vulvodynia is an idiopathic chronic pain disorder and a leading cause of dyspareunia, or pain associated with sexual intercourse, for women. The key pathophysiological features of vulvodynia are vaginal hyperinnervation and nociceptor sensitization. These features have been described consistently by research groups over the past 30 years, but currently there is no first-line recommended treatment that targets this pathophysiology.

Human Dorsal Root Ganglia.

Sensory neurons with cell bodies situated in dorsal root ganglia convey information from external or internal sites of the body such as actual or potential harm, temperature or muscle length to the central nervous system. In recent years, large investigative efforts have worked toward an understanding of different types of DRG neurons at transcriptional, translational, and functional levels. These studies most commonly rely on data obtained from laboratory animals.

Extracellular and intracellular sphingosine-1-phosphate distinctly regulates exocytosis in chromaffin cells.

Sphingosine-1-phosphate (S1P) is an essential bioactive sphingosine lipid involved in many neurological disorders. Sphingosine kinase 1 (SphK1), a key enzyme for S1P production, is concentrated in presynaptic terminals. However, the role of S1P/SphK1 signaling in exocytosis remains elusive.

Innervation Changes Induced by Inflammation in the Murine Vagina.

Vulvodynia is a prevalent chronic pain disorder associated with high medical costs and often ineffective treatments. The major pathological feature is proliferation of vaginal nerve fibers. This study aimed to develop a highly reproducible animal model to study neuroproliferation in the vagina and aid the identification of appropriately targeted treatments for conditions such as vulvodynia.

Sphingosine-1-Phosphate and the S1P Receptor Initiate Neuronal Retraction via RhoA/ROCK Associated with CRMP2 Phosphorylation.

The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an assay, and virtually all neurons responded with a rapid retraction of neurites and growth cone collapse which were associated with RhoA and ROCK activation.

Peptidergic nerve fibers in the urethra: Morphological and neurochemical characteristics in female mice of reproductive age.

Background: Peptidergic nerve fibers provide important contributions to urethral function. Urethral innervation of female mice is not well documented.

Aims: To determine the distribution and projection sites of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the urethra of wild-type control mice and compare innervation characteristics between the proximal and distal urethra of young nullipara and older multipara mice.

Morphological and neurochemical differences in peptidergic nerve fibers of the mouse vagina.

The vagina is innervated by a complex arrangement of sensory, sympathetic, and parasympathetic nerve fibers that contain classical transmitters plus an array of neuropeptides and enzymes known to regulate diverse processes including blood flow and nociception. The neurochemical characteristics and distributions of peptide-containing nerves in the mouse vagina are unknown. This study used multiple labeling immunohistochemistry, confocal maging and analysis to investigate the presence and colocalization of the peptides vasoactive intestinal polypeptide (VIP), calcitonin-gene related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and the nitric oxide synthesizing enzyme neuronal nitric oxide synthase (nNOS) in nerve fibers of the murine vaginal wall.

Local Sphingosine Kinase 1 Activity Improves Islet Transplantation.

Pancreatic islet transplantation is a promising clinical treatment for type 1 diabetes, but success is limited by extensive β-cell death in the immediate posttransplant period and impaired islet function in the longer term. Following transplantation, appropriate vascular remodeling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase (SK) pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown.

Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs Hippocampal Neuron Excitability and Spatial Working Memory .

Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P) within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P) and with a special focus on the hippocampus.

A study to investigate needle insertion at Shenshu (BL23) to puncture psoas major muscle.

Objective: It is unknown whether the psoas major muscle, thought to be a key muscle for treatment of lower back pain, can be punctured at Shenshu (BL23).

Methods: Twelve dissected specimens were used for studying the needling pathway of BL23 by perpendicularly inserting the depth-measuring blade of a vernier caliper at BL23. Dimensions of psoas muscle were measured.

Sphingosine kinase 2-deficiency mediated changes in spinal pain processing.

Chronic pain is one of the most burdensome health issues facing the planet (as costly as diabetes and cancer combined), and in desperate need for new diagnostic targets leading to better therapies. The bioactive lipid sphingosine 1-phosphate (S1P) and its receptors have recently been shown to modulate nociceptive signaling at the level of peripheral nociceptors and central neurons. However, the exact role of S1P generating enzymes, in particular sphingosine kinase 2 (Sphk2), in nociception remains unknown.

Primary afferent neurons containing calcitonin gene-related peptide but not substance P in forepaw skin, dorsal root ganglia, and spinal cord of mice.

In mice dorsal root ganglia (DRG), some neurons express calcitonin gene-related peptide (CGRP) without substance P (SP; CGRP(+) SP(-) ). The projections and functions of these neurons are unknown. Therefore, we combined in vitro axonal tracing with multiple-labeling immunohistochemistry to neurochemically define these neurons and characterize their peripheral and central projections.

Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor.

The biolipid sphingosine-1-phosphate (S1P) is an essential modulator of innate immunity, cell migration, and wound healing. It is released locally upon acute tissue injury from endothelial cells and activated thrombocytes and, therefore, may give rise to acute post-traumatic pain sensation via a yet elusive molecular mechanism. We have used an interdisciplinary approach to address this question, and we find that intradermal injection of S1P induced significant licking and flinching behavior in wild-type mice and a dose-dependent flare reaction in human skin as a sign of acute activation of nociceptive nerve terminals.

Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn.

Background: Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB4. Most express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed to be glutamatergic nociceptors but their terminations within the spinal cord are unknown.

Expression profile of the sphingosine kinase signalling system in the lung of patients with chronic obstructive pulmonary disease.

Aims: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Despite its importance, treatment methods are limited and restricted to symptomatic care, highlighting the urgent need for new treatment options. Tissue damage in COPD is thought to result from an inability of the normal repair processes with accumulation of apoptotic material and impaired clearance of this material by macrophages in the airways.

Sensory innervation of the external genital tract of female guinea pigs and mice.

Introduction: The structural and neurochemical characterization of the sensory innervation of the external genitalia of females is poorly known.

Aims:   To immunohistochemically map the sensory innervation of external genitalia and surrounding structures of female guinea pigs and mice.

Methods: Large-diameter sensory fibers, presumably mechanoreceptors, were identified by their immunoreactivity to neuron-specific enolase (NSE) or vesicular glutamate transporter 1 (VGluT1).

Genetic evidence for involvement of neuronally expressed S1P₁ receptor in nociceptor sensitization and inflammatory pain.

Sphingosine-1-phosphate (S1P) is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain.

Antibodies interfering with the type 3 muscarinic receptor pathway inhibit gastrointestinal motility and cholinergic neurotransmission in Sjögren's syndrome.

Objective: In primary Sjögren's syndrome (SS), impairment of the gastrointestinal (GI) tract is common, and includes reduced esophageal motor function, delayed gastric emptying, and abnormalities in colonic motility; the pathogenesis is as yet unknown. We undertook this study to investigate the role of functional antibodies to the type 3 muscarinic receptor (M3R) in GI dysfunction associated with primary SS.

Methods: Muscle strip and whole-organ functional assays were used to determine whether IgG with anti-M3R activity from patients with primary SS disrupted neurotransmission in tissue from throughout the mouse GI tract.