BackgroundClinical data on osteoarthritis (OA) suggest widespread changes in sensory function that vary during the progression of OA. In previous studies on a surgically-induced animal model of OA we have observed that changes in structure and gene expression follow a variable trajectory over the initial days and weeks. To investigate mechanisms underlying changes in sensory function in this ...
PubMed Central
... deficient (Nf1+/-, Nf1-/-, and exon23a-/-) dorsal root ganglion (DRG) sensory neurons and superior cervical ganglion (SCG) sympathetic neurons to ...
DTIC Science & Technology
ABSTRACT: In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via beta3 adrenoceptors linked to Gs protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG ...
PubMed
... afferents and depolarization of DRG neurons via a photosensitive mechanism. Naunyn Schmiedebergs Arch. Pharmacol 356:619�625. ... ...
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Altered dorsal root ganglion (DRG) function is associated with neuropathic pain following spinal nerve injury. However, compression of the cauda equina and dorsal rhizotomy proximal to the DRG do not induce significant pain, whereas in the spinal nerve and peripheral nerve, injury distal to the DRG does induce neuropathic pain. Caspase ...
The rat L5/6 facet joint is multisegmentally innervated from the L1 to L6 dorsal root ganglia (DRG). Tumor necrosis factor (TNF) is a known mediator of inflammation. It has been reported that satellite cells are activated, produce TNF and surround DRG neurons innervating L5/6 facet joints after facet injury. In the current study, ...
Previously, it was believed that the lumbar intervertebral disc was innervated segmentally by dorsal root ganglion (DRG) neurons via the sinuvertebral nerves. Recently, it was demonstrated using retrograde tracing methods that the lower disc (L5-L6) is innervated predominantly by upper (L1 and L2) DRG neurons via ...
Here we present a two-compartment in vitro model in which embryonic rat dorsal root ganglia (DRG) neurons are cultured separately from their target dorsal horn neurons. Although separated, synaptic contact can be established between the peripheral and central neurons since the system allows the ...
We compared the expression of chemokine receptor CCR2 protein in the dorsal root ganglia (DRG) injured by the chronic constriction injury (CCI), the spinal nerve ligation (SNL) and a chronic compression of DRG (CCD). Each of these injuries produced the same significant increase in CCR2 protein in the DRG, as assessed by Western blot ...
Neurite outgrowth is a fundamental step in establishing proper neuronal connections in the developing central nervous system. Dynamic control of outgrowth has been attributed to changes in growth cone Ca(2+) levels in response to extracellular cues. Here we have investigated a possible role for Ca(2+) permeable kainate (KA) receptors in regulating neurite outgrowth of ...
Dorsal root ganglion (DRG) sensory neurons transmit all somatosensory information from the trunk region of the body. erbb3 mutant zebrafish do not form DRG neurons because the neural crest cells that generate them migrate aberrantly. Here we report that homozygous erbb3 mutants appear to swim and feed normally, and ...
Nuclear factor kappa B (NF-?B) is a transcription factor, which is translocated to the nucleus when activated. Herein, we demonstrate immunohistochemically that electrical, chemical, and thermal stimuli, applied to the skin of mice, all induced nuclear translocation and phosphorylation of NF-?B in dorsal root ganglia (DRG) neurons. The latency of this ...
We established that neurons present in dorsal root ganglia (DRG), similar to leukocytes, express a wide variety of receptors for cytokines, chemokines, opioids, anandamide and other neuropeptides.
Cancer.gov
Insulin signaling depends on tyrosine phosphorylation of insulin receptor substrates (IRSs) to mediate downstream effects; however, elevated serine phosphorylation of IRS impairs insulin signaling. Here, we investigated IRS protein expression patterns in dorsal root ganglia (DRG) of mice and whether their signaling was affected by diabetes. Both IRS1 and IRS2 are expressed in ...
Most, if not all, dorsal root ganglion (DRG) neurons use the neurotransmitter glutamate. There are, however, conflicting reports of the percentages of DRG neurons that express glutaminase (GLS), the enzyme that synthesizes glutamate, ranging from 30% to 100% of 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 ...
In this study we have investigated the action of bradykinin (Bk) on cultured neonatal rat dorsal root ganglion (DRG) cells, with the aim of elucidating whether the neuronal response to Bk is influenced by association with non-neuronal satellite cells.Bradykinin (100 nm) evoked an inward current (IBk) in 51 of 58 ...
Peripheral nerve injury induces the retrograde degeneration of dorsal root ganglion (DRG) cells, which affects predominantly the small-diameter cutaneous afferent neurons. This study compares the time-course of retrograde cell death in cutaneous and muscular DRG cells after peripheral nerve transection as well as ...
This study investigated whether neuronal inhibitor of DNA binding 2 (Id2), a regulator of basic helix-loop-helix (bHLH) transcription factors, can activate the intrinsic neuritogenetic mode of dorsal root ganglion (DRG) neurons in adult mice following spinal cord injury (SCI). First, the Id2 developmental expression profile of ...
Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using ...
Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic ...
TREK-1, TREK-2 and TRAAK are mechanosensitive two-pore domain K(+) (K(2P)) channels thought to be involved in the attenuation of mechanotransduction. Because colon inflammation is associated with colon mechanohypersensitivity, we hypothesized that the role of these channels in colon sensory (dorsal root ganglion, DRG) neurons would be reduced by colon ...
Rabies virus infection of dorsal root ganglia (DRG) was studied in vitro with cultured adult mouse DRG neurons. Recent in vivo studies of transgenic mice that express the yellow fluorescent protein indicate that neuronal process degeneration, involving both dendrites and axons, occurs in mice infected with the ...
Exposure to oxidative stress causes health problems, including sensory neuron neuropathy and pain. Rotenone is a toxin used to generate intracellular oxidative stress in neurons. However, the mechanism of toxicity in dorsal root ganglion (DRG) neurons has not been characterized. Melastatin-like transient receptor ...
The expression of major cytoskeletal protein mRNAs was studied in adult rat dorsal root ganglion (DRG) neurons after crushing either their central or peripheral branch axons. mRNA levels in DRG neurons were examined by quantitative in situ hybridization with radiolabeled cDNA probes specific for the ...
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BackgroundThe dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full ...
Loss of function of the FIG4 gene causes Charcot-Marie-Tooth disease (CMT)-4J with many features also found in motor neuron disease (MND). Mechanisms for the degeneration are unknown. We investigated this using Fig4-deficient pale tremor (plt) mice, a mouse model of CMT4J. Ultrastructural studies in sensory neurons of dorsal root ganglion ...
Dorsal root ganglia (DRG) contain somatosensory neurons of diverse sensory modalities. Among these different types of sensory neurons, the molecular mechanisms that regulate the development and specification of touch neurons are the least well understood. We took a candidate approach and searched for transcription ...
Increasing evidence indicates that both the nerve growth factor (NGF) and adrenergic systems play a very important role in the development of nociception. However, there is little information concerning the functional interactions between these two systems in the dorsal root ganglion (DRG). The present study tested the hypothesis that NGF could affect ...
BackgroundATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference ...
Innervation of the joint with thinly myelinated and unmyelinated sensory nerve fibres is crucial for the occurrence of joint pain. During inflammation in the joint, sensory fibres show changes in the expression of receptors that are important for the activation and sensitization of the neurones and the generation of joint pain. We recently reported that both neurokinin 1 ...
Tetrodotoxin-resistant (TTX-R) Na(+) channels play a key role in the generation of action potentials in nociceptive dorsal root ganglion (DRG) neurons and are an important target for the proinflammatory mediator prostaglandin E(2), which augments these currents. Prostaglandin D(2) (PGD(2)) is released in the tissue together with prostaglandin E(2), and it ...
To investigate the intracellular signal transduction pathways involved in regulating the gene expression of brain-derived neurotrophic factor (BDNF) in primary afferent neurons, we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons after peripheral inflammation and ...
Synapses between nociceptive dorsal root ganglion (DRG) neurons and spinal cord dorsal horn neurons represent the first loci for transmission of painful stimuli. Our knowledge of the molecular organization and development of these synapses is sparse due, partly, to a lack of a reliable model system that reconstitutes synaptogenesis ...
J. Neurochem. (2011) 118, 841-854. ABSTRACT: Following various types of nerve injury, cyclooxygenase 2 and prostaglandin E2 (PGE2) are universally and chronically up-regulated in injured nerves and contribute to the genesis of neuropathic pain. Persistent high levels of PGE2 likely exert chronic effects on nociceptive dorsal root ganglion (DRG) neurons. In ...
Preservation of neural stem cells (NSCs) in the adult peripheral nervous system (PNS) has recently been confirmed. However, it is not clear whether peripheral NSCs possess predestined, bona fide phenotypes or a response to innate developmental cues. In this study, we first demonstrated the longevity, multipotency, and high fidelity of sensory features of postmigrating adult dorsal root ganglia ...
Prior to parturition the non-pliable uterine cervix undergoes a ripening process ("softens" and dilates) to allow a timely passage of the fetus at term. The exact mechanism(s) triggering and involved in cervical ripening are unknown, though evidence for a role for sensory neurons and their contained neuropeptides is emerging. Moreover, an apparent increase in neuropeptide ...
The proneural transcription factor neurogenin 1 (neurog1) has been shown to be a key regulator of dorsal root ganglion (DRG) neuron development. Here we use a novel transgenic zebrafish line to demonstrate that the neural crest population that gives rise to DRG neurons becomes fate-restricted to a ...
BackgroundInjury to the peripheral branch of dorsal root ganglia (DRG) neurons prior to injury to the central nervous system (CNS) DRG branch results in the regeneration of the central branch. The exact mechanism mediating this regenerative trigger is not fully understood. It has been proposed that following peripheral injury, the ...
Our previous study showed localization of glutamate receptor 1 (GluR1) mRNA in neurons of the pigeon spinal cord, suggesting glutamatergic input from intrinsic and extrinsic origins. The present study examined localization of vesicular glutamate transporter 2 (VGLUT2) mRNA to confirm an extrinsic origin of glutamatergic neurons in the dorsal root ganglion ...
The rat L5/6 facet joint, from which low back pain can originate, is multisegmentally innervated from the L1 to L5 dorsal root ganglia (DRG). Sensory fibers from the L1 and L2 DRG are reported to non-segmentally innervate the paravertebral sympathetic trunks, while those from the L3 to L5 DRGs segmentally innervate the L5/6 facet joint. Tumor necrosis ...
Afferent information from the lung is conveyed both to the brainstem and to the spinal cord by primary afferent fibres originating from vagal sensory (jugular-nodose ganglion complex=JNC) and dorsal root ganglion (DRG) neurons, respectively. Most interest, so far, has been paid to the vagal pathway while much less is known about spinal afferents. Here we ...
Atrophy of dorsal root ganglia (DRG) and thinning of dorsal roots (DR) are hallmarks of Friedreich's ataxia (FRDA). Many previous authors also emphasized the selective vulnerability of larger neurons in DRG and thicker myelinated DR axons. This report is based on a systematic reexamination of DRG, DR and ventral ...
AbstractElevated blood glucose is a key initiator of mechanisms leading to diabetic neuropathy. Increases in glucose induce acute mitochondrial oxidative stress in dorsal root ganglion (DRG) neurons, the sensory neurons normally affected in diabetic neuropathy, whereas Schwann cells are largely unaffected. We propose that activation of ...
The neuropeptide substance P is synthesized in a proportion of neurons of the peripheral and central nervous system, and the receptor for substance P, tachykinin NK(1) receptor, has been identified in numerous areas of the central nervous system including the spinal cord. The present investigation was to confirm the existence of tachykinin NK(1) receptor on rat dorsal root ...
BackgroundLentivector-mediated gene delivery into the dorsal root ganglion (DRG) is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. In this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the ...
Corticotropin-releasing factor (CRF) is a peptide involved in the activation of the hypothalamic-pituitary-adrenal (HPA) axis. CRF is distributed not only along the HPA axis but also throughout pain-relevant anatomical sites. CRF elicits potent antinociception at the three main levels of pain transmissions: namely, the brain, spinal cord, and peripheral sensory neurons. The ...
The dorsal root ganglion (DRG) contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling. Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K+ channels; however, the ...
1. Topographical distribution patterns of dorsal root ganglion (d.r.g.) cutaneous neurones providing innervation to various body surfaces were examined in doublypithed Discoglossus pictus frogs. 2. Using electrophysiological methods, sensory neurones innervating back skin were observed to predominate on the dorsal ganglionic surfaces, ...
Target-dependent cell death of different sub-populations of sensory neurons may be regulated by different trophic factors. To investigate this possibility, we have taken advantage of the fact that the fractions of muscle sensory and cutaneous sensory neurons in chicken dorsal root ganglia (DRG) are probably different at different ...
Glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells and maintains thiol redox in the cells. GSH depletion has been implicated in the neurobiology of sensory neurons. Because the mechanisms that lead to melastatin-like transient receptor potential 2 (TRPM2) channel activation/inhibition in response to glutathione depletion and 2-aminoethyldiphenyl ...
In this work we have studied the intracellular localization properties of the Gag and Env proteins of Moloney murine leukemia virus (MLV) and human immunodeficiency virus (HIV) in dorsal root ganglion (DRG) neurons of rat. These neurons form thick bundles of axons, which facilitates protein localization studies by immunofluorescence ...
The collapsin and semaphorin family of extracellular proteins contributes to axonal path finding by repulsing axons and collapsing growth cones. To explore the mechanism of collapsin-1 action, we expressed and purified a truncated collapsin-1-alkaline phosphatase fusion protein (CAP-4). This protein retains biological activity as a DRG growth cone collapsing agent and ...
The basic-helix-loop-helix transcription factor HeyL is expressed at high levels by neural crest progenitor cells (NCPs) that give rise to neurons and glia in dorsal root ganglia (DRG). Since HeyL expression was observed in these NCPs during the period of neurogenesis, we generated HeyL null mutants to help examine the factor's role in ganglion ...
Considerable interest has been focused on inducing RNA interference (RNAi) in neurons to study gene function and identify new targets for disease intervention. Although small interfering RNAs (siRNAs) have been used to silence genes in neurons, in vivo delivery of RNAi remains a major challenge limiting its applications. We have developed a highly ...
In adult Wistar rats a segment of the right sciatic nerve was grafted to the right dorsal funiculus of the spinal cord (SC). After survivals of 25-54 weeks a solution of the retrograde fluorescent cytoplasmatic tracer Fast Blue (FB) was injected into the SC and microgranules of the retrograde fluorescent nuclear tracer Diamidino Yellow (DY) were inserted into the graft. DY labelled ...
In this study, we investigated whether nitric oxide (NO) modulated injury-induced neuropeptide Y (NPY) releasing and c-Fos expression in the cuneate nucleus (CN) after median nerve transection (MNT). We first examined the temporal changes of neuronal nitric oxide synthase (nNOS) expression in the dorsal root ganglion (DRG) and CN after MNT. Following MNT, ...
We have established that neurons present in dorsal root ganglia (DRG), like leukocytes, express a wide variety of receptors for cytokines, chemokines, opioids, anandamide and neuropeptides.
Cisplatin causes apoptosis of DRG neurons in vitro and in vivo that can be prevented by high dose NGF. Design of a neuronal rescue strategy for patients receiving cisplatin will be facilitated by knowledge of the mechanism by which cisplatin causes DRG death. Inhibition of the fas receptor/ligand interaction ...
BackgroundAdenosine 5'-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve entrapment (SNE).ResultsAfter SNE, rats develop long-lasting decreases in ...
Cultures of dorsal root ganglia (DRG) exposed to direct current (DC) and pulsed electromagnetic fields (PEMF) were compared to controls and DRG treated with NGF. The authors objectives were to determine: (1) the effects of all paradigms on neurite growth and (2) whether there is a correlation between the electric field, or the magnetic field using the ...
Spinal nerves and their associated dorsal root ganglion (DRG) cells can be subject to mechanical deformation and hypoxia associated with pathology such as disc herniation, spinal stenosis and spine trauma. There is very limited information on the response of adult DRG neurons to such stressors. In this study we used an in vitro ...
Expression of the cell adhesion molecule TAG-1 is down-regulated in adult brain, with the exception of certain areas exhibiting structural plasticity. Here, we present evidence that TAG-1 expression persists also in adult rat spinal cord and dorsal root ganglia (DRG), and can be up-regulated after injury. On Western blots of adult tissue, TAG-1 is detected as a 135-kDa band, ...
BackgroundA chronic compressed dorsal root ganglion (CCD) in rat produces pain behavior and an enhanced excitability of neurons within the compressed ganglion. Kir2.1 is an inwardly rectifying potassium channel that acts to stabilize the resting potential of certain cell types. We hypothesized that an inducible expression of Kir2.1 channels in CCD neurons ...
The enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) is associated with memory and its alpha isoform is critical for development of activity-induced synaptic changes. Therefore, we hypothesized that CaMKII is involved in altered function of dorsal root ganglion (DRG) neurons after neuronal injury. To test this hypothesis, ...
BackgroundGene transfer to nociceptive neurons of the dorsal root ganglia (DRG) is a promising approach to dissect mechanisms of pain in rodents and is a potential therapeutic strategy for the treatment of persistent pain disorders such as neuropathic pain. A number of studies have demonstrated transduction of DRG ...
Chronic compression (CCD) of the dorsal root ganglion (DRG) is a model of human radicular pain produced by intraforaminal stenosis and other disorders affecting the DRG, spinal nerve or root. Previously we examined electrophysiological changes in small-diameter L3 and L4 DRG neurons treated with CCD; the present ...
Muscle spindle afferent (MSA) neurons can show rapid and sustained firing. Immunostaining for the ?3 isoform of the Na(+)/K(+)-ATPase (?3) in some large dorsal root ganglion (DRG) neurons and large intrafusal fibres suggested ?3 expression in MSAs (Dobretsov et al. 2003), but not whether ?3-immunoreactive DRG ...
Muscle spindle afferent (MSA) neurons can show rapid and sustained firing. Immunostaining for the ?3 isoform of the Na+/K+-ATPase (?3) in some large dorsal root ganglion (DRG) neurons and large intrafusal fibres suggested ?3 expression in MSAs (Dobretsov et al. 2003), but not whether ...
Cutaneous nerves are increased in atopic dermatitis, and itch is a prominent symptom. We studied the functional interactions between eosinophils and nerves in human and mouse skin and in culture. We demonstrated that human atopic dermatitis skin has eosinophil granule proteins present in the same region as increased nerves. Transgenic mice in which interleukin-5 (IL-5) expression is driven by a ...
A prolonged exposure to vibration stimuli triggers pathological changes with many later manifested symptoms. Early vibration-induced changes are still not very well explored. Therefore, short 30 min vibration period per day with frequency 60 Hz repeated for 10 days was used, and the retrograde axonal transport from the sciatic nerve, the expression of calcitonin gene-related peptide (CGRP) and ...
Most small unmyelinated neurons in adult rat dorsal ganglia (DRG) express one or more of the co-receptors targeted by glial cell line-derived neurotrophic factor (GDNF), neurturin and artemin (GFR?1, GFR?2 and GFR?3 respectively). The function of these GDNF family ligands (GFLs) is not fully elucidated but recent evidence suggests GFLs could function in ...
Background? Peripheral irritation-induced sensory plasticity may involve catecholaminergic innervation of sensory neurons in the dorsal root ganglia (DRG). Methods? Catecholaminergic fiber outgrowth in the thoracolumbar DRG (T13-L2) was examined by tyrosine hydroxylase (TH) immunostaining, or by sucrose-potassium phosphate-glyoxylic ...
The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether ...
Controlled clinical trials of nicotine transdermal patch for treatment of ulcerative colitis have been shown to improve histological and global clinical scores of colitis. Here we report that nicotine (1 ?M) suppresses in vitro hyperexcitability of colonic dorsal root ganglia (DRG) (L1�L2) neurons in the ...
Abnormal hyperexcitability of primary sensory neurons plays an important role in neuropathic pain. Voltage-gated potassium (Kv) channels regulate neuronal excitability by affecting the resting membrane potential and influencing the repolarization and frequency of the action potential. Here we determined changes in Kv channels in dorsal root ganglion ...
We demonstrated recently that superoxide anion levels are elevated in prevertebral sympathetic ganglia of deoxycorticosterone acetate-salt hypertensive rats and that this superoxide anion is generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase. In this study we compared the reduced nicotinamide-adenine dinucleotide phosphate oxidase enzyme system of dorsal root ganglion ...
Secreted Slit proteins have previously been shown to signal through Roundabout (Robo) receptors to negatively regulate axon guidance and cell migration. During vertebrate development, Slit proteins have also been shown to stimulate branching and elongation of sensory axons and cortical dendrites. In this study, Slit1/Robo2 mRNA and protein expressions were detected in adult rat dorsal root ...
Neurotransmitter release normally requires calcium triggering. However, the somata of dorsal root ganglion (DRG) neurons possess a calcium-independent but voltage-dependent secretion (CIVDS) in addition to the classic calcium-dependent secretion (CDS). Here, we investigated the physiological role of CIVDS and the contributions of CIVDS and CDS induced by ...
Although most investigations of the mechanisms underlying chronic pain after spinal cord injury (SCI) have examined the CNS, recent studies have shown that nociceptive primary afferent neurons display persistent hyperexcitability and spontaneous activity in their peripheral branches and somata in dorsal root ganglia (DRG) after SCI. This suggests that ...
The enzyme 3alpha-hydroxysteroid oxido-reductase (3alpha-HSOR) catalyzes the synthesis and bioavailability of 3alpha,5alpha-neurosteroids as allopregnanolone (3alpha,5alpha-THP) which activates GABA(A) receptors and blocks T-type calcium channels involved in pain mechanisms. Here, we used a multidisciplinary approach to demonstrate that 3alpha-HSOR is a cellular target the modulation of which in ...
AIM: To investigate the silencing effects of pAd-shRNA-pleiotrophin (PTN) on PTN in pancreatic cancer cells, and to observe the inhibition of pAd-shRNA-PTN on neurite outgrowth from dorsal root ganglion (DRG) neurons in vitro.METHODS: PAd-shRNA-PTN was used to infect pancreatic cancer BxPC-3 cells; assays were conducted for knockdown of the PTN gene on the ...
Many chronic pain conditions including complex regional pain syndrome are exacerbated by sympathetic activity. In animal models, sympathetic fibers sprout into the dorsal root ganglia (DRG) after peripheral nerve injury, forming abnormal connections with sensory neurons. However, functional studies of sympathetic-sensory connections have been limited ...
Sympathoexcitatory reflex is characterized by an increase in blood pressure and sympathetic nerve activity. P2X? receptors in SCG neurons are involved in increasing sympathoexcitatory reflex after myocardial ischemic (MI) injury. The present study is aimed to explore the effects of oxymatrine (Oxy) on the transmission of myocardial ischemic signaling mediated by P2X? receptors ...
Matrix metalloproteinase 9 (MMP9) and MMP2 are important in the development and maintenance of neuropathic pain behavior induced by peripheral nerve injury. The enzymatic activity of MMP9 and MMP2 is balanced specifically by tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2, respectively. In present study, we measured the effect of peripheral nerve injury on the expression of TIMP1 and ...
OBJECTIVE The therapeutic potential of exendin-4, an agonist of the glucagon-like peptide-1 receptor (GLP-1R), on diabetic polyneuropathy (DPN) in streptozotocin (STZ)-induced diabetic mice was investigated. RESEARCH DESIGN AND METHODS The presence of the GLP-1R in lumbar dorsal root ganglion (DRG) was evaluated by immunohistochemical analyses. DRG ...
Some cases of lumbar disc herniation with contralateral radiculopathy have been reported. Many investigators explained this clinical syndrome from several aspects. However, to our best knowledge, there is no explanation on the basis of molecular changes in the contralateral dorsal root ganglia (DRG) until now. We firstly explored the expression of activating transcription ...
J. Neurochem. (2011) 10.1111/j.1471-4159.2011.07456.x ABSTRACT: Painful neuropathy is one of the most serious complications of diabetes and remains difficult to treat. The muscarinic acetylcholine receptor (mAChR) agonists have a profound analgesic effect on painful diabetic neuropathy. Here we determined changes in T-type and high voltage-activated Ca(2+) channels (HVACCs) and their regulation by ...
The vast majority of people living with human immunodeficiency virus type 1 (HIV-1) have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are ...
In this paper we describe new actions of nimesulide and paracetamol in cultured peripheral neurons isolated from rat dorsal root ganglia (DRG). Both drugs were able to decrease in a dose-dependent fashion the number of cultured DRG neurons showing translocation of protein kinase C epsilon (PKC?) caused by exposure ...
Fibroblast growth factors (FGFs) promote axon growth during development and regeneration of the nervous system. Among the four types of FGF receptors (FGFRs), FGFR1 is expressed in adult sensory neurons of dorsal root ganglia (DRG), and overexpression of FGFR1 promotes FGF-2-induced elongative axon growth in vitro. Ligand-induced activation of FGFR1 is ...
A significant loss of neurons in the dorsal root ganglia (DRG) has been reported in animal models of peripheral nerve injury. Neonatal sensory neurons are more susceptible than adult neurons to axotomy- or nerve growth factor (NGF) withdrawal-induced cell death. To develop therapies for preventing irreversible ...
Transient receptor potential V3 (TRPV3) and TRPV4 are heat-activated cation channels expressed in keratinocytes. It has been proposed that heat-activation of TRPV3 and/or TRPV4 in the skin may release diffusible molecules which would then activate termini of neighboring dorsal root ganglion (DRG) neurons. Here we show that adenosine triphosphate (ATP) is ...
Neuropathic pain is usually persistent and there is no effective treatment. Activation of P2X(3) receptor subtype in primary sensory neurons is involved in neuropathic pain. Sodium ferulate (SF) is an active principle from Chinese herbal medicine and has anti-inflammatory activities. This study observed the effects of SF on the hyperalgesia mediated by P2X(3) receptor of rats ...
We have studied the effect of key neurotrophic factors (NTFs) on morphology, levels of the vanilloid receptor-1 (TRPV1) and responses to capsaicin in adult human sensory neurons in vitro. Avulsed dorsal root ganglia (DRG, n = 5) were cultured with or without a combination of nerve growth factor (NGF), glial cell (line)-derived growth factor (GDNF) and ...
Itching is a common symptom in dermatologic diseases and causes restless scratching of the skin, which aggravates the condition. The mechanism of the itch sensation, however, is enigmatic. The present study included behavioral tests and electrophysiological recordings from rat dorsal root ganglion (DRG) neurons in vivo to analyze the response to pruritic ...
Neuregulin-1? (NRG-1?) signaling has multiple functions in neurons. To assess NRG-1? on neurite outgrowth and neuronal migration in vitro, organotypic dorsal root ganglion (DRG) neuronal culture model was established. Neurite outgrowth and neuronal migration were evaluated using this culture ...
The rat L5/6 facet joint, from which low-back pain can originate, is multisegmentally innervated from the L1 to L5 dorsal root ganglions (DRGs). Sensory fibers from the L1 and L2 DRGs are reported to non-segmentally innervate the paravertebral sympathetic trunks, whilst those from the L3 to L5 DRGs segmentally innervate the L5/6 facet joint. In the current study, characteristics of sensory ...
Thermosensitive TRP channels display unique thermal responses, suggesting distinct roles mediating sensory transmission of temperature. However, whether relative expression of these channels in dorsal root ganglia (DRG) is altered in nerve injury is unknown. We developed a multiplex ribonuclease protection assay (RPA) to quantify rat TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and ...
ABSTRACT Carbon disulfide (CS(2)) is a neurotoxic industrial solvent and widely used in the vulcanization of rubber, rayon, cellophane and adhesives. Although the neurotoxicity of CS(2) has been recognized for over a century, the precise mechanism of neurotoxic action of CS(2) remains unknown. In the present study, embryonic rat DRG explants culture model was established. ...
Estradiol attenuates the ATP-induced increase of intracellular calcium concentration ([Ca(2+) ](i) ) in rat dorsal root ganglion (DRG) neurons by blocking the L-type voltage gated calcium channel (VGCC). Because ATP is a putative nociceptive signal, this action may indicate a site of estradiol regulation of pain. In other neurons, ...
While a number of chronic pain conditions are much more prevalent in women than men, the role of estrogen in regulating nociception remains unclear. Estrogen receptors (ER) are known to be expressed in various parts of the nociceptive pathway, including in the small-sized primary sensory neurons of the dorsal root ganglion (DRG). This study evaluated the ...
Nucleotide-activated P2X channels and P2Y metabotropic receptors participate in nociceptive signaling. Agonist availability is regulated by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), -2, -3, and -8, a family of enzymes that hydrolyze extracellular ATP to generate ADP (a P2Y agonist) and AMP. They provide a major source of extracellular AMP, the substrate for adenosine production by ...
BackgroundIt has been demonstrated that lysophosphatidic acid (LPA) released from injury tissue and transient receptor potential vanilloid 1 (TRPV1) receptor are implicated in the induction of chronic pain. In the present study we examined whether an interaction between LPA receptor LPA1 and TRPV1 in dorsal root ganglion (DRG) ...
The H+-gated acid-sensing ion channels (ASICs) are expressed in dorsal root ganglion (DRG) neurones. Studies with ASIC knockout mice indicated either a pro-nociceptive or a modulatory role of ASICs in pain sensation. We have investigated in freshly isolated rat DRG neurones whether ...
BackgroundWhole cell patch clamp recording and intracellular Ca2+ imaging were carried out on rat cultured dorsal root ganglion (DRG) neurones to characterize the actions of crude extracts and purified samples from Red Sea soft corals. The aim of the project was to identify compounds that would alter the excitability of ...
We recently developed a genetic transneuronal tracing approach that allows for the study of circuits that are altered by nerve injury. We generated transgenic (ZW-X) mice in which expression of a transneuronal tracer, wheat germ agglutinin (WGA), is induced in primary sensory neurons, but only after transection of their peripheral axon. By following the transneuronal transport ...
In dorsal root ganglion sections numerous small-to medium-sized neurons were found to exhibit extensive colocalization of the bradykinin receptor 2, the interleukin-1 receptor 1 and G protein-coupled receptor kinase 2. Application of bradykinin to cultured DRG neurons caused substantial internalization of the bradykinin 2 receptor ...
Newborn animals recover from neurological injury to a greater extent than adults in spite of the greater vulnerability of developing neurons to retrograde or transneuronal degeneration (Kennard, '42; Goldman, '74; Prendergast and Stelzner, '76; Bregman and Goldberger, '82, '83). The cellular mechanisms underlying this "infant lesion effect" are incompletely understood (Bregman ...
Direct injection of agents into the dorsal root ganglia (DRGs) offers the opportunity to manipulate sensory neuron function at a segmental level to explore pathophysiology of painful conditions. However, there is no described method that has been validated in detail for such injections in adult rats. We have found that 2 ?l of dye injected through a pulled glass pipette ...
Interleukin-10 prevents transition of a physiological inflammatory reaction to a pathological state that may result in neuropathic pain. We studied bilateral changes of IL-10 protein levels in L4-L5 and C7-C8 dorsal root ganglia (DRG) after a chronic constriction injury (CCI) of either L4-L5 spinal nerves (pCCI) or the sciatic nerve (dCCI). Rats undergoing pCCI or dCCI were ...
We have developed a model in which inflammation contiguous to and within a dorsal root ganglion (DRG) was generated by local application of complete Freund�s adjuvant (CFA) to the L4 lumbar spinal nerve as it exits from the intervertebral foramen. The periganglionic inflammation (PGI) elicited a marked reduction in withdrawal threshold to mechanical stimuli and an increase ...
Estrogens were originally identified as the primary sex steroid hormones in females and regulators of reproductive function and sexual behavior, but it has long been suggested that estrogens also have local effects on the somatosensory system at the spinal cord level. It is well known that the effects of estrogens are mediated by nuclear estrogen receptors (ERs) through genomic action, but ...
The somata of dorsal root ganglion (DRG) neurons release neurotransmitters and neuropeptides. In addition to the conventional Ca2+-dependent secretion (CDS), Ca2+-independent but voltage-dependent secretion (CIVDS) also occurs in the somata of DRG neurons. Electrical stimulation induces both CDS and CIVDS, which ...
Nerve regeneration and functional recovery have been a major issue following injury of nerve tissues. Electrospun nanofibers are known to be suitable scaffolds for neural tissue engineering applications. In addition, modified substrates often provide better environments for neurite outgrowth. This study was conducted to determine if multi-walled carbon nanotubes (MWCNTs)-coated electrospun poly ...
This study was performed to determine the impact of the inflammatory mediator prostaglandin E(2) (PGE(2)) on the biophysical properties of tetrodotoxin resistant voltage-gated Na(+) currents (TTX-R I(Na)) in colonic dorsal root ganglion (DRG) neurons. TTX-R I(Na) was studied in DRG neurons from thoracolumbar (TL: ...
The expression and role of monocyte chemoattractant protein-1 (MCP-1) in the rat dorsal root ganglion (DRG) and spinal cord was evaluated in the lumbar 5 ventral rhizotomy (L5 VR) model of neuropathic pain. MCP-1 protein expression in the L4/L5 DRG neurons following L5 VR peaked after 3 days, and then declined. Immunohistochemistry ...
BackgroundThe present study aims to investigate the role of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons in chronic pain including thermal hyperalgesia and mechanical allodynia. Chronic inflammatory nociception of rats was produced by intraplantar injection of complete Freund's adjuvant (CFA) and data was collected ...
induced or repressed by nerve regeneration, including galanin, neuropeptide Y, neurofilament, glial cell is transported throughout the regenerating axonal process (Fig. 2B). That the stained cells are regenerating DRG of neurons to regenerate an axon after injury is determined by both the surrounding environment and factors
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of an organism. For Pseudo-nitzschia, for example, more domoic acid is produced under silica or phosphorus limitation than under nitrogen limitation, likely due to the fact that domoic acid is a nitrogen to produce more domoic acid when grown on urea than on other nitrogen sources (Armstrong and Kudela 00
It has previously been observed that expression of chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor CCR2 is upregulated by dorsal root ganglion (DRG) neurons in association with rodent models of neuropathic pain. MCP-1 increases the excitability of nociceptive neurons after a peripheral nerve injury, while ...
dependent. Here, we show that the cytokine interleukin-6 (IL-6) is upregulated in DRG neurons after either a conditioning lesion or treatment with dibutyryl-cAMP. In culture, IL-6 allows neurons to grow in the presence inhibition by myelin both in vitro and in vivo, effectively mimicking the conditioning lesion. Blocking IL-6
Neurons and Mediates Inflammatory Heat Hyperalgesia through TRPV1 Sensitization Zhi-Ye Zhuang,1 Haoxing Xu and NGF produce heat hyperalgesia by activating their respective TRPV1 (transient receptor potential early induction of hyperalgesia. In acutely dissociated DRG neurons, the capsaicin- induced TRPV1
Metal nanoparticles, due to their unique properties and important applications in optical, magnetic, thermal, electrical, sensor devices and cosmetics, are beginning to be widely manufactured and used. This new and rapidly growing field of technology warrants a thorough examination of the material�s bio-compatibility and safety. Ultra-small particles may adversely affect living cells and ...
BACKGROUND & AIMS: To investigate the peripheral sensory effects of repeated stress in patients with postinfectious irritable bowel syndrome (IBS), we tested whether stress following self-limiting bacterial colitis increases colonic dorsal root ganglia (DRG) nociceptive signaling. METHODS: C57BL/6 mice were infected with Citrobacter rodentium. Stress was induced using a ...
Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and ...
Cultures of neonatal and adult dorsal root ganglion (DRG) neurons are commonly used in in vitro models to study the ion channels and signaling events associated with peripheral sensation under various conditions. Differential responsiveness between neonatal and adult DRG neurons to physiological or pathological ...
Calcitonin gene-related peptide (CGRP) and/or substance P (SP) immunoreactivity as well as isolectin B4 (IB4) binding are commonly used to define peptidergic and non-peptidergic nociceptor populations, respectively. While this demarcation is well supported in the mouse, there is accumulating evidence to suggest it is not so in the rat. Hence, this ...
The molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-{beta}-peptide (A{beta}), which plays a critical role in the neurodegeneration that triggers the disease. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are members of the nuclear receptor family. We report here that ...
Before parturition the uterine cervix undergoes a ripening process ("softens" and dilates) to allow passage of the fetus at term. The exact mechanism(s) responsible for cervical ripening are unknown, though a role for peptidergic sensory neurons is emerging. Previous work demonstrated that administration of substance P (SP) to ovariectomized rats caused events associated with ...
Cyclic GMP has been proposed to regulate axonal development, but the molecular and cellular mechanisms underlying the formation of axon branches are not well understood. Here, we report the use of rodent embryonic sensory neurons from the dorsal root ganglion (DRG) to demonstrate the role of cGMP signaling in axon branching and to identify the downstream ...
BackgroundLyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and ...
P2X receptors on dorsal root ganglion (DRG) neurons have been strongly implicated in pathological nociception after peripheral nerve injuries or inflammation. However, nothing is known of a role for purinergic receptors in neuropathic pain produced by a chronic compression of DRG (CCD) � an injury that may accompany an intraforaminal ...
A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE ...
The paired-type homeodomain transcription factor Prrxl1 (also known as Drg11) is a key regulator of the differentiation and survival of dorsal root ganglia (DRG) and spinal nociceptive neurons in pre- and perinatal stages. Prrxl1(-/-) mice exhibit abnormalities in DRG-spinal projections, defects in superficial ...
BackgroundNeuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P ...
Vesicular glutamate transporters (VGLUTs) have been extensively studied in various neuronal systems, but their expression in visceral sensory and autonomic neurons remains to be analyzed in detail. Here we studied VGLUTs type 1 and 2 (VGLUT(1) and VGLUT(2) , respectively) in neurons innervating the mouse colorectum. Lumbosacral and ...
Brain-derived neurotrophic factor (BDNF) plays a critical role in the development of the central and peripheral nervous systems, and also in neuronal survival after injury. The actions of BDNF are mediated by its high-affinity receptors TrkB and p75NTR. Recent studies have shown that proneurotrophins bind p75NTR and sortilin with high affinity, and trigger apoptosis of ...
Primary afferent neurons are functionally heterogeneous. To determine whether this functional heterogeneity reflects, in part, heterogeneity in the regulation of the concentration of intracellular Ca2+ ([Ca2+]i), the magnitude and decay of evoked Ca2+ transients were assessed in ...
1. Experiments based on teased fiber recording from rat sciatic nerve have shown that a small proportion of primary afferent neurons in intact dorsal root ganglia (DRGs) fire spontaneously. The prevalence of this discharge is substantially increased if the sciatic nerve has been chronically injured. 2. We now show that in most cases this ongoing DRG ...
A large body of evidence has demonstrated that the ectopic discharges of action potentials in primary afferents, resulted from the abnormal expression of voltage gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons following peripheral nerve injury are important for the development of neuropathic pain. However, how nerve injury affects the ...
BackgroundA direct role of sodium channels in pain has recently been confirmed by establishing a monogenic link between SCN9A, the gene which encodes sodium channel Nav1.7, and pain disorders in humans, with gain-of-function mutations causing severe pain syndromes, and loss-of-function mutations causing congenital indifference to pain. Expression of sodium channel ...
Electrical stimulation at the time of nerve repair promotes motoneurons to reinnervate appropriate pathways leading to muscle and stimulates sensory neurons to regenerate. The present experiments examine the effects of electrical stimulation on the specificity of sensory axon regeneration. The unoperated rat femoral cutaneous branch is served by 2-3 times more ...
The present study has disclosed for the first time the distribution and peripheral nerve pathways of autonomic and primary afferent neurons projecting to the bulbourethral gland (BG) in a mammalian species, the pig (n = 5), using combined retrograde tracing and cutting the hypogastric (n = 3) or pelvic (n = 3) nerve. Neurons projecting to the right BG were ...
The cell bodies of sensory neurons in the dorsal root ganglion (DRG) are enveloped by satellite glial cells (SGCs). In an animal model of intervertebral foraminal stenosis and low-back pain, a chronic compression of the DRG (CCD) increases the excitability of neuronal cell bodies in the compressed ganglion. The ...
Capsaicin is a neurotoxin selective for C- and Adelta-type neurons. Systemic treatment with capsaicin is known to reduce this subpopulation in the dorsal root ganglia (DRG) of neonatal rats. To better understand the effects of capsaicin on adult afferent fibers, we examined DRG neurons retrogradely labeled by an ...
The cervical facet joint is implicated as one of the most common sources of chronic neck pain, owing to its rich nociceptive innervation and susceptibility to injurious mechanical loading. Injuries to the facet joint and its ligament can induce inflammation in the joint and spinal cord. Inflammatory molecules which are known to have a role in pain can also stimulate the integrated stress response ...
Cisplatin has been in use for 40 years, primarily for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Neurotoxicity occurs in up to 30% of patients and is dose-limiting for both drugs. The neuropathy is characterized by selective sensory loss in the extremities. Cisplatin treatment is associated with high levels of Pt-DNA ...
The organic cation/carnitine transporters OCTN1 and OCTN2 are related to other organic cation transporters (OCT1, OCT2, and OCT3) known for transporting oxaliplatin, an anticancer drug with dose-limiting neurotoxicity. In this study, we sought to determine whether OCTN1 and OCTN2 also transported oxaliplatin and to characterize their functional expression and contributions to its ...
STUDY DESIGN.: Immunohistological analysis of punctured disc after application of a p38 MAP kinase inhibitor. OBJECTIVE.: To examine effect of direct application on dorsal root ganglion (DRG) neurons innervating damaged rat discs. SUMMARY OF BACKGROUND DATA.: Degeneration of lumbar discs is one cause of low back pain. Pathogenesis may involve sensory nerve ...
The mechanisms underlying neuropathic pain induction are very complex but might involve abnormal spontaneous activity in the sensory dorsal root ganglion (DRG). Voltage-gated sodium channels in the DRG are essential for the genesis of abnormal spontaneous neuronal activity. In this study, we examined the changes in expression of the ...
ABSTRACT: BACKGROUND: The neuropeptide, calcitonin gene-related peptide (CGRP) has been proposed to be a regulator of the development of morphine analgesic tolerance and thereby could be a target to reduce the induction of this phenomenon under clinical conditions. However, the mechanisms of CGRP regulation are unclear. We investigated here the possible role of the extracellular signal-regulated ...
BackgroundThe pathogenic role of brain derived neurotrophic factor (BDNF) in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity.MethodsA longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG) and spinal cords were removed at various ...
In women, clinical studies suggest that functional pain syndromes such as irritable bowel syndrome, interstitial cystitis, and fibromyalgia, are co-morbid with endometriosis, chronic pelvic pain, and others diseases. One of the possible explanations for this phenomenon is visceral cross-sensitization in which increased nociceptive input from inflamed reproductive system organs sensitize ...
The perception of pain is initiated by the transduction of noxious stimuli through specialized ion channels and receptors expressed by primary nociceptive neurons. The molecular mechanisms that orchestrate the expression and function of ion channels relevant for pain processing are poorly understood. We demonstrate here a central role of the transcription factor ...
Cell bodies of afferent neurons located in lumbosacral dorsal root ganglia (DRG) provide Adelta- and C-fibres to the urinary bladder, reporting bladder wall tension, volume and noxious stimuli. Recent studies suggested an involvement of muscarinic acetylcholine receptors (mAChRs) not only in detrusor contractility but also in modulating afferent function, ...
In addition to the classic genomic effects, it is well known that glucocorticoids also have rapid, nongenomic effects on neurons. In the present study, the effect of corticosterone (CORT) on ATP-induced Ca(2+) mobilization in cultured dorsal root ganglion (DRG) neurons were detected with confocal laser scanning microscopy using ...
Earlier, we showed that streptozocin (STZ)-induced type 1 diabetes in rats leads to the development of painful peripheral diabetic neuropathy (PDN) manifested as thermal hyperalgesia and mechanical allodynia accompanied by significant enhancement of T-type calcium currents (T-currents) and cellular excitability in medium-sized dorsal root ganglion (DRG) ...
Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance ...
factor (BDNF), a secreted factor emanating from proprioceptive sensory terminals, induces the synaptic on Sensory-Derived BDNF Signaling (A) 30.5 � 0.7% (n = 464 neurons; 3 mice) of p7 lumbar DRG neurons express BDNF mRNA. (B) $85% (n = 3 mice) of p7 Pv+ proprioceptive neurons express BDNF mRNA. (C) 81.5 � 3.8% ...
detected PLCb3 protein in the soma area of the DRG neurons (see Figure S1 in the Supplemental Data-specific ligand effects. Adenosine 50 -triphos- phate (ATP), Uridine 50 -triphosphate (UTP), capsaicin is a nonselective agonist that acts on the P2X and P2Y re- ceptors; capsaicin is a specific agonist for TRPV1; BK
BackgroundTumor suppressor WOX1 (also named WWOX or FOR) is known to participate in neuronal apoptosis in vivo. Here, we investigated the functional role of WOX1 and transcription factors in the delayed loss of axotomized neurons in dorsal root ganglia (DRG) in ...
This study investigated the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity in cats subjected to the removal of dorsal root ganglia (DRG). Following partial ganglionectomy, the number of BDNF-positive varicosities from spared L6 DRG decreased significantly. This reduction was observed at 3 days post operation (dpo) in spinal lamina II ...
Radiolabelled glucosamine was injected into L-7 dorsal root ganglion (DRG) of rabbits. At several different times after injection DRG, lumbosacral trunks (LST) and sciatic nerves (SN) removed and gangliosides extracted. Two and 3 weeks after injection the amounts of radioactivity in the ganglioside fractions of LST SN were significantly higher than at days ...
Radiolabelled glucosamine was injected into L-7 dorsal root ganglion (DRG) of rabbits. At several different times after injection DRG, lumbosacral trunks (LST) and sciatic nerves (SN) were removed and gangliosides extracted. Two and 3 weeks after injection the amounts of radioactivity in the ganglioside fractions of LST and SN were significantly higher ...
Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were ...
Thiamine monophosphatase (TMPase, also known as Fluoride-resistant acid phosphatase or FRAP) is a classic histochemical marker of small- to medium-diameter dorsal root ganglia (DRG) neurons and has primarily been studied in the rat. Previously, we found that TMPase was molecularly identical to Prostatic acid phosphatase (PAP) using mice. In addition, PAP ...
Neurokinins (NK) released from terminals of dorsal root ganglion (DRG) neurons may control firing of these neurons by an autofeedback mechanism. In this study we used patch clamp recording techniques to determine if NKs alter excitability of rat L4-S3 DRG neurons by modulating K(+) currents. In ...
The transcription factor Sox11 is expressed at high levels in developing sensory neurons and injured adult neurons but little is known about its transcriptional targets and function. In this study we examined the role of Sox11 using Neuro2a neuroblastoma cells and cultured mouse dorsal root ganglia (DRG) neurons. ...
Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 influences growth-associated protein 43 (GAP-43) expression and activates the extracellular signal-regulated protein kinase (ERK1/2) and the phosphatidylinositol 3-kinase (PI3K)/Akt ...
Pain is a common and debilitating accompaniment of neuropathy that occurs as a complication of diabetes. In the current study, we examined the effect of continuous release of gamma amino butyric acid (GABA), achieved by gene transfer of glutamic acid decarboxylase (GAD67) to dorsal root ganglia (DRG) in vivo using a non-replicating herpes simplex virus (HSV)-based vector (vG) ...
States of phosphorylation of neurofilament proteins were examined in the perikarya of rat sensory and motor neurons between 3 and 28 d following either a distal transection [6-7 cm from the L4-L5 dorsal root ganglia (DRG)] or a proximal transection (1-2 cm from the L4-L5 DRG) of the sciatic nerve. Paraffin sections of the right ...
The existence of retrograde cell death in sensory dorsal root ganglion (DRG) cells after peripheral nerve injury is well established. However, with respect to retrograde motoneuron death after peripheral nerve injury, available data are conflicting. This may partly be due to the cell counting techniques used. In the present study, quantitative morphometric methods have been ...
Low concentrations (0.11-1.7 microg ml(-1)) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The ...
Low concentrations (0.11-1.7 �g ml ? 1) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity ...
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Mechanical stimuli impinging on the skin are converted into electrical signals by mechanically gated ion channels located at the peripheral nerve endings of dorsal root ganglion (DRG) neurons. Under inflammatory conditions sensory neurons are commonly sensitised to mechanical stimuli; a putative mechanism that may contribute to such ...
Understanding the cues that guide axons and how we can optimize these cues to achieve directed neuronal growth is imperative for neural tissue engineering. Cells in the local environment influence neurons with a rich combination of cues. This study deconstructs the complex mixture of guidance cues by working at the biomimetic interface - isolating the ...
In this work we set up an in vitro model, based on organotypic cultures of spinal cord slices and dorsal root ganglia explants from P7 rats, embedded in a collagen matrix and cultured under the same conditions. As specific reinnervation of end-organs is still an unresolved issue in peripheral nerve research, we characterized a model that allows us to compare under the same conditions motor and ...
The nerve growth factor precursor (proNGF) may function as a death-inducing ligand that mediates its apoptotic effects via p75NTR. ProNGF-induced apoptosis is postulated to be dependent upon membrane expression of the sortilin receptor, which interacts with p75NTR to promote a high affinity-binding site for proNGF. Here, we explore the expression of ...
We established spontaneously immortalized Schwann cell lines from long-term cultures of adult Fischer 344 rat dorsal root ganglia (DRG) and peripheral nerves. One of these cell lines, designated immortalized Fischer rat Schwann cells 1 (IFRS1), showed spindle-shaped morphology; immunoreactivity for S100, p75 neurotrophin receptor (p75(NTR) ), glial fibrillary acidic protein ...
Large-conductance Ca(2+)-activated K(+) (BK(Ca), MaxiK) channels are important for the regulation of neuronal excitability. Peripheral nerve injury causes plasticity of primary afferent neurons and spinal dorsal horn neurons, leading to central sensitization and neuropathic pain. However, little is known about changes in the BK(Ca) ...
Large-conductance Ca2+-activated K+ (BKCa, MaxiK) channels are important for the regulation of neuronal excitability. Peripheral nerve injury causes plasticity of primary afferent neurons and spinal dorsal horn neurons, leading to central sensitization and neuropathic ...
To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-cell patch clamp technique, the effects of dragon's blood and the combined effects of three components (cochinchinenin A, cochinchinenin B, and ...
We investigated changes in pain behavior after injection of acetic acid in the hindpaws of rats with L5 spinal nerve ligation (SNL)-induced neuropathy. We also examined immunoreactivity for acid-sensing ion channel 3 (ASIC3) in the dorsal root ganglion (DRG) of rats with L5 SNL. Two weeks after SNL, the withdrawal threshold to a mechanical stimulus was significantly lower in ...
Objectives.? We aim to determine the effects of Botulinum toxin type A (BTX-A) on neuropathic pain behavior and the expression of P2X(3) receptor in dorsal root ganglion (DRG) in rats with neuropathic pain induced by L5 ventral root transection (L5 VRT). Methods.? Neuropathic pain was induced by L5 VRT in male Sprague-Dawley rats. Either saline or BTX-A was administered to the ...
We investigated the effects of chronic compression (CCD) of the L3 and L4 dorsal root ganglion (DRG) on pain behavior in the mouse and on the electrophysiological properties of the small-diameter neuronal cell bodies in the intact ganglion. CCD is a model of human radicular pain produced by intraforaminal stenosis and other disorders affecting the ...
We have previously shown that axonal growth from a subset of sensory neurons was promoted by keratinocytes when the two cell types were co-cultured in a low calcium medium. This phenomenon involves the production of one or several diffusible factors. Here we show that the neuritogenic effect of keratinocytes was significantly reduced in the case of rat primary sensory dorsal ...
BackgroundNeuronal transduction by adeno-associated viral (AAV) vectors has been demonstrated in cortex, brainstem, cerebellum, and sensory ganglia. Intrathecal delivery of AAV serotypes that transduce neurons in dorsal root ganglia (DRG) and spinal cord offers substantial opportunities to 1) further study mechanisms underlying chronic ...
For quantitative studies of rat dorsal root ganglion (DRG) in experimental models stereological principles offer a number of different techniques. The application, however, requires knowledge of the anatomy and cytology of the ganglion, considerations of sampling and choosing between the many estimators available. For number and volume estimates in thick glycolmethacrylate ...
BackgroundATP-sensitive potassium (KATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal KATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we ...
Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses ...
BACKGROUNDInjury of a spinal nerve or dorsal root ganglion (DRG) during selective spinal nerve blocks is a potentially serious complication that has not been adequately investigated. Our hypothesis was that local anesthetic injection into these structures may result in an inflammatory response and hyperalgesia.METHODSWe evaluated inflammatory and behavioral responses after ...
BackgroundThe pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S) in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S ...
BackgroundFps/Fes and Fer are the only two members of a distinct subclass of cytoplasmic protein tyrosine kinases. Fps/Fes was previously implicated in Semaphorin 3A (Sema3A)-induced growth cone collapse signaling in neurons from the dorsal root ganglion (DRG) through interaction with and phosphorylation of the Sema3A receptor component PlexinA1, and ...
Chronic neuropathic pain caused by peripheral nerve injury is associated with global changes in gene expression in damaged neurons. To understand the molecular mechanisms underlying neuropathic pain, it is essential to elucidate how nerve injury alters gene expression and how the change contributes to the development and maintenance of chronic pain. MicroRNAs are ...