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Sample records for hyperglycemic dorsal root

  1. Expression of interleukin-1 beta in rat dorsal root ganglia

    NARCIS (Netherlands)

    Copray, JCVM; Mantingh, [No Value; Brouwer, N; Biber, K; Kust, BM; Liem, RSB; Huitinga, [No Value; Tilders, FJH; Van Dam, AM; Boddeke, HWGM

    2001-01-01

    The expression of interleukin-lp was examined in dorsal root ganglion (DRG) neurons from adult rats using non-radioactive in Situ hybridization and immunocytochemistry. At all spinal levels, approximately 70% of the DRG neurons appeared to express IL-1 beta mRNA: about 80% of these DRG neurons

  2. Oscillatory interaction between dorsal root excitability and dorsal root potentials in the spinal cord of the turtle

    DEFF Research Database (Denmark)

    Delgado-Lezama, R; Perrier, J F; Hounsgaard, J

    1999-01-01

    The response to dorsal root stimulation, at one to two times threshold, was investigated in the isolated cervical enlargement of the turtle spinal cord. At frequencies near 10 Hz the synaptic response in motoneurons and the cord dorsum potential, after an initial lag time, oscillated in amplitude...

  3. Purification of Dorsal Root Ganglion Neurons from Rat by Immunopanning

    OpenAIRE

    Zuchero, J. Bradley

    2014-01-01

    Dorsal root ganglion neurons (DRGs) are sensory neurons that facilitate somatosensation and have been used to study neurite outgrowth, regeneration, and degeneration and PNS and CNS myelination. Studies of DRGs have relied on cell isolation strategies that generally involve extended culture in the presence of antimitotic agents or other cytotoxic treatments that target dividing cells. The surviving cells typically are dependent on serum for growth. Other methods, involving purification of DRG...

  4. Position of dorsal root ganglia in the lumbosacral region in patients with radiculopathy.

    Science.gov (United States)

    Moon, Hyun Seog; Kim, Yeon Dong; Song, Bang Hoon; Cha, Young Deog; Song, Jang Ho; Lee, Mi Hyeon

    2010-12-01

    When applying pulsed radiofrequency on dorsal root ganglia for treating chronic lower back pain, maximum efficiency can be expected when a needle is placed 1-2 cm peripheral to the dorsal root ganglion. The object of this study is to analyze images taken after adding contrast to transforaminal epidural injection, categorize root ganglia according to anatomical position, and provide a reference for efficient needle positioning in applying pulsed radiofrequency on dorsal root ganglia. From January 2008 to January 2009, 457 patients who visited our hospital for root pain or radiculopathy were treated with transforaminal epidural injection on the nerve roots based on the dermatome of the painful area. Anteroposterior views were taken after injection of contrast. A virtual line was made by connecting the internal and external parts of the spinal pedicle from the contrast images. Then the dorsal root ganglia were categorized as intraspinal (IS), intraforaminal (IF), or extraforaminal (EF). In the fourth lumbar spine, dorsal root ganglia positions were 48% IF, 41% IS, and 6% EF. In the fifth lumbar spine, dorsal root ganglia positions were 75% IF, 10% IS, and 6% EF. In the first sacral spine, dorsal root ganglia locations were 8% IF and 83% IS. Positional categorization of dorsal root ganglia according to contrast images was proven to be good anatomical references for effective radiofrequency or blocking of dorsal root ganglia.

  5. [Expression of Sema3A and NP-1 in spinal cord and spared dorsal root ganglion after partial dorsal root rhizotomy of cat].

    Science.gov (United States)

    Ding, Yan; Zhang, Wei; Huang, Qian; Peng, Jin; Zhao, Xiu-jun; Xu, Ai-li; Zhou, Xue

    2008-01-01

    To investigate the expression of semaphorin 3A (Sema3A) and neuropilin 1 (NP-1) in spinal cord and dorsal root ganglion after partial dorsal root rhizotomy. 15 adult cats were used for this study and divided into 3 groups: normal control group, 7 d and 14 d postoperative groups (7Th day and 14th day groups) undergoing unilateral partial dorsal root rhizotomy. The L3, L5 and L6 segments of spinal cord and L6 dorsal root ganglia (DRG) in operated side were made into frozen sections. By immunohistochemistry ABC method, the sections of spinal cord were stained with specific Sema3A antibody, and L6 DRG were stained with NP-1 antibody. The mean optical density (OD) of Sema3A immunoreactivity in dorsal horn was measured and the number of NP-1 positive medium-small sized neurons in spared DRG was counted. After partial dorsal root rhizotomy, in L3 segment the expression of Sema3A decreased in 7th day group (0.25 +/- 0. 14) compared with that in normal group(0. 37 +/- 0.87) (P P NP-1 positive medium-small sized neurons in spared DRG (30.85 +/- 10.26) was decreased in 7th day group (P P NP-1 in L6 DRG after partial root rhizotomy may be involved in collateral sprouting of spared root in superficial lamina.

  6. The Molecular Fingerprint of Dorsal Root and Trigeminal Ganglion Neurons

    Directory of Open Access Journals (Sweden)

    Douglas M. Lopes

    2017-09-01

    Full Text Available The dorsal root ganglia (DRG and trigeminal ganglia (TG are clusters of cell bodies of highly specialized sensory neurons which are responsible for relaying information about our environment to the central nervous system. Despite previous efforts to characterize sensory neurons at the molecular level, it is still unknown whether those present in DRG and TG have distinct expression profiles and therefore a unique molecular fingerprint. To address this question, we isolated lumbar DRG and TG neurons using fluorescence-activated cell sorting from Advillin-GFP transgenic mice and performed RNA sequencing. Our transcriptome analyses showed that, despite being overwhelmingly similar, a number of genes are differentially expressed in DRG and TG neurons. Importantly, we identified 24 genes which were uniquely expressed in either ganglia, including an arginine vasopressin receptor and several homeobox genes, giving each population a distinct molecular fingerprint. We compared our findings with published studies to reveal that many genes previously reported to be present in neurons are in fact likely to originate from other cell types in the ganglia. Additionally, our neuron-specific results aligned well with a dataset examining whole human TG and DRG. We propose that the data can both improve our understanding of primary afferent biology and help contribute to the development of drug treatments and gene therapies which seek targets with unique or restricted expression patterns.

  7. Expressing Constitutively Active Rheb in Adult Dorsal Root Ganglion Neurons Enhances the Integration of Sensory Axons that Regenerate Across a Chondroitinase-Treated Dorsal Root Entry Zone Following Dorsal Root Crush.

    Science.gov (United States)

    Wu, Di; Klaw, Michelle C; Kholodilov, Nikolai; Burke, Robert E; Detloff, Megan R; Côté, Marie-Pascale; Tom, Veronica J

    2016-01-01

    While the peripheral branch of dorsal root ganglion neurons (DRG) can successfully regenerate after injury, lesioned central branch axons fail to regrow across the dorsal root entry zone (DREZ), the interface between the dorsal root and the spinal cord. This lack of regeneration is due to the limited regenerative capacity of adult sensory axons and the growth-inhibitory environment at the DREZ, which is similar to that found in the glial scar after a central nervous system (CNS) injury. We hypothesized that transduction of adult DRG neurons using adeno-associated virus (AAV) to express a constitutively-active form of the GTPase Rheb (caRheb) will increase their intrinsic growth potential after a dorsal root crush. Additionally, we posited that if we combined that approach with digestion of upregulated chondroitin sulfate proteoglycans (CSPG) at the DREZ with chondroitinase ABC (ChABC), we would promote regeneration of sensory axons across the DREZ into the spinal cord. We first assessed if this strategy promotes neuritic growth in an in vitro model of the glial scar containing CSPG. ChABC allowed for some regeneration across the once potently inhibitory substrate. Combining ChABC treatment with expression of caRheb in DRG significantly improved this growth. We then determined if this combination strategy also enhanced regeneration through the DREZ after dorsal root crush in adult rats in vivo. After unilaterally crushing C4-T1 dorsal roots, we injected AAV5-caRheb or AAV5-GFP into the ipsilateral C5-C8 DRGs. ChABC or PBS was injected into the ipsilateral dorsal horn at C5-C8 to digest CSPG, for a total of four animal groups (caRheb + ChABC, caRheb + PBS, GFP + ChABC, GFP + PBS). Regeneration was rarely observed in PBS-treated animals, whereas short-distance regrowth across the DREZ was observed in ChABC-treated animals. No difference in axon number or length between the ChABC groups was observed, which may be related to intraganglionic inflammation induced by the

  8. The dorsal root ganglion as a therapeutic target for chronic pain

    NARCIS (Netherlands)

    A.L. Liem (Liong); Van Dongen, E. (Eric); F.J.P.M. Huygen (Frank); P. Staats (Peter); J. Kramer (Jeffery)

    2016-01-01

    textabstractChronic neuropathic pain is a widespread problem with negative personal and societal consequences. Despite considerable clinical neuroscience research, the goal of developing effective, reliable, and durable treatments has remained elusive. The critical role played by the dorsal root

  9. Dorsal root ganglion compression as an animal model of sciatica and low back pain

    OpenAIRE

    Lin, Xiao-Yu; Yang, Jing; LI, HUI-MING; Hu, San-Jue; Xing, Jun-Ling

    2012-01-01

    As sciatica and low back pain are among the most common medical complaints, many studies have duplicated these conditions in animals. Chronic compression of the dorsal root ganglion (CCD) is one of these models. The surgery is simple: after exposing the L4/L5 intervertebral foramina, stainless steel rods are implanted unilaterally, one rod for each vertebra, to chronically compress the lumbar dorsal root ganglion (DRG). Then, CCD can be used to simulate the clinical conditions caused by steno...

  10. Pulsed and continuous radiofrequency current adjacent to the cervical dorsal root ganglion of the rat induces late cellular activity in the dorsal horn.

    NARCIS (Netherlands)

    Zundert, J. van; Louw, A.J. de; Joosten, E.A.J.; Kessels, A.G.H.; Honig, W.; Dederen, P.J.W.C.; Veening, J.G.; Vles, J.S.; Kleef, M. van

    2005-01-01

    BACKGROUND: Pulsed radiofrequency treatment has recently been described as a non-neurodestructive or minimally neurodestructive alternative to radiofrequency heat lesions. In clinical practice long-lasting results of pulsed radiofrequency treatment adjacent to the cervical dorsal root ganglion for

  11. Up-regulation of Robo1 in dorsal root ganglia after sciatic nerve ...

    African Journals Online (AJOL)

    Yomi

    2012-01-05

    Jan 5, 2012 ... peripheral nervous system, this study investigated the expression profile of Robo1 in the dorsal root ganglia (DRG) of adult rats following sciatic nerve transection (SNT). Adult Sprague-Dawley rats that were untreated (n = 8), or received SNT (n = 40), were analyzed. DRG from each treatment group at days.

  12. Up-regulation of Robo1 in dorsal root ganglia after sciatic nerve ...

    African Journals Online (AJOL)

    To better understand the role of Robo in peripheral nervous system, this study investigated the expression profile of Robo1 in the dorsal root ganglia (DRG) of adult rats following sciatic nerve transection (SNT). Adult Sprague-Dawley rats that were untreated (n = 8), or received SNT (n = 40), were analyzed. DRG from each ...

  13. Whole transcriptome expression of trigeminal ganglia compared to dorsal root ganglia in Rattus Norvegicus

    DEFF Research Database (Denmark)

    Kogelman, Lisette Johanna Antonia; Christensen, Rikke Elgaard; Pedersen, Sara Hougaard

    2017-01-01

    The trigeminal ganglia (TG) subserving the head and the dorsal root ganglia (DRG) subserving the rest of the body are homologous handling sensory neurons. Differences exist, as a number of signaling substances cause headache but no pain in the rest of the body. To date, very few genes involved in...

  14. Dorsal root potential produced by a TTX-insensitive micro-circuitry in the turtle spinal cord

    DEFF Research Database (Denmark)

    Russo, R E; Delgado-Lezama, R; Hounsgaard, J

    2000-01-01

    1, The mechanisms underlying the dorsal root potential (DRP) were studied in transverse slices of turtle spinal cord. DRPs were evoked by stimulating one filament in a dorsal root and were recorded from another such filament. 2. The DRP evoked at supramaximal stimulus intensity was reduced...

  15. Diabetic hyperglycemic hyperosmolar syndrome

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000304.htm Diabetic hyperglycemic hyperosmolar syndrome To use the sharing features on this page, please enable JavaScript. Diabetic hyperglycemic hyperosmolar syndrome (HHS) is a complication of ...

  16. Comparison of efficacy between dorsal root entry zone lesioning and selective dorsal rhizotomy for spasticity of cerebral origin.

    Science.gov (United States)

    Sitthinamsuwan, Bunpot; Phonwijit, Luckchai; Khampalikit, Inthira; Nitising, Akkapong; Nunta-Aree, Sarun; Suksompong, Sirilak

    2017-12-01

    Severe spasticity adversely affects patient functional status and caregiving. No previous study has compared efficacy between dorsal root entry zone lesioning (DREZL) and selective dorsal rhizotomy (SDR) for reduction of spasticity. This study aimed to investigate the efficacy of DREZL and SDR for attenuating spasticity, and to compare efficacy between these two methods. All patients who underwent DREZL, SDR, or both for treatment of intractable spasticity caused by cerebral pathology at Siriraj Hospital during 2009 to 2016 were recruited. Severity of spasticity was assessed using Modified Ashworth Scale (MAS) and Adductor Tone Rating Scale (ATRS). Ambulatory status was also evaluated. Fifteen patients (13 males) with a mean age of 30.3 ± 17.5 years were included. Eight, six, and one patient underwent DREZL, SDR, and combined cervical DREZL and lumbosacral SDR, respectively. Eight of ten patients with preoperative bed-bound status had postoperative improvement in ambulatory status. Spasticity was significantly reduced in the DREZL group (p SDR group (p SDR was effective in both pediatric and adult spasticity patients. A significantly greater reduction in spasticity as assessed by MAS score (p SDR. DREZL is more effective for reducing spasticity, but is more destructive than SDR. DREZL should be preferred for bed-ridden patients, and SDR for ambulatory patients. Both operations are helpful for improving ambulatory status. Gait improvement was observed only in patients who underwent SDR. Adult patients with spasticity of cerebral origin benefit from SDR.

  17. Dorsal root activity evoked by stimulation of vagina-cervix-uterus junction in the rat.

    Science.gov (United States)

    Tovar, Anibal; Lara-Garcia, Miguel; Cruz, Yolanda; Pacheco, Pablo

    2013-02-16

    In the present study, we characterized the evoked electrical activity from T(13) to S(2) dorsal roots (DRs) during glass probe-stimulation of the vagina-cervix-uterus junction (VCUJ) of female Wistar rats. The results showed that gentle stimulation of VCUJ evoked high-amplitude electrical activity in L(3) and L(6) DRs. Hypogastric or pelvic nerve transection failed to abolish this activity. L(6)-S(1) spinal trunk transection abolished the high-amplitude electrical activity evoked in L(6) DR, while transection of the lumbosacral trunk blocked the high-amplitude electrical activity evoked in L(3) DR. These data suggest that during copulation, penile intromission likely activates the low-threshold sensory receptors of the VCUJ, thereby evoking sensory neural activity that enters the spinal cord via L(3) and L(6) dorsal roots, whose axons travel through the lumbosacral trunk and pudendal nerve. Copyright © 2013. Published by Elsevier B.V.

  18. Antidromic discharges in dorsal roots of decerebrate cats. II: studies during treadmill locomotion.

    Science.gov (United States)

    Beloozerova, Irina N; Rossignol, Serge

    2004-01-23

    In a previous companion paper [Brain Res. 846 (1999) 87-105] we have shown that the dorsal root activity of a decerebrate cat is composed of both orthodromic and antidromic discharges as determined by spike triggered averaging (STA). Furthermore we have shown that, during fictive locomotion in decerebrate and paralyzed cats, antidromic discharges peak in different parts of locomotion cycle but mainly in the flexion phase. In the present study, we have recorded unit potentials from dorsal rootlets during treadmill locomotion in order to understand better the role of movement-related feedback in the generation of antidromic potentials. The unitary activity of 92 antidromically discharging units was recorded in proximal stumps of cut dorsal roots, and that of 20 such units was recorded in uncut roots using two bipolar Ag/AgCl electrodes in both cases. The activity of 80% (74/92) units in cut filaments and of 70% (14/20) units in uncut ones was phasewise related to stepping movements. The peaks of activity of different units occurred during different phases of the step cycle both in cut and uncut filaments. In most cases, the peak of activity was superimposed upon a background of sustained discharge. After blocking the orthodromic flow in a filament (local anesthesia or distal section), the antidromic discharges continued to peak during the same phase but the rate of the discharges increased. We conclude that movement-related afferent feedback significantly modulates the antidromic discharges in dorsal roots during treadmill locomotion. We suggest that these antidromic discharges have a role in controlling afferent feedback during movement.

  19. Three dimensional-magnetic resonance imaging of dorsal root. Ganglion in lumbosacral disease

    Energy Technology Data Exchange (ETDEWEB)

    Taira, Gaku [Tokyo Medical Coll. (Japan)

    1997-07-01

    Magnetic resonance imaging (MRI) is commonly used for the diagnosis of lumbosacral disease. However, there are certain pitfalls in the use of this imaging technique. In particular, MRI is inadequate for accurate diagnosis of lateral spinal root lesions. Furthermore, it is also difficult to show the root ganglion of both sides on a plane by classical 2D-MRI. Moreover 2D-coronal views do not show several roots in one image because each lumbosacral nerve root is on a different plane. We have developed a new method of three-dimensional MRI (3D-MRI) which enables a stereoscopic view of the spinal cord and both sides of spinal nerve roots in one image. We evaluated three techniques of 3D-MRI, including rapid imaging spin echo (RISE), small tip angle gradient echo (STAGE) and short TI inversion recovery (STIR), in 30 patients with lumbar disc herniation. In a separate anatomical study lumbosacral nerve roots and dorsal root ganglion (DRG) were investigated by 3D-MRI in 20 normal subjects. In a pathophysiological study the use of 3D-MRI defects the signal changes following damage to the spinal nerve roots or ganglion in 70 patients. Our results indicated that the STIR method is the best for identifying abnormalities of the spinal cord, roots and intervertebral disc. It was possible to image the lateral part of damaged nerve roots. The S1 angulations and length were significantly smaller than those of others (p<0.05). The S1 DRG was oval and was the largest. With regard to signal changes in damaged root ganglion, a good correlation between root compression and root edema was detected by basic experiments. We are currently examining the relationship between the damaged root ganglion, pain and sensory disturbance. This study showed that the dorsal root ganglion plays an important role in sensory control of radiculopathy. In conclusion, our new data show a close relationship between sensory loss, pain and DRG finding on 3D-MRI. (author)

  20. Identification of some lectin IB4 binding proteins in rat dorsal root ganglia.

    Science.gov (United States)

    Fullmer, Joseph M; Riedl, Maureen S; Higgins, LeeAnn; Elde, Robert

    2004-08-06

    Lectins are proteins that bind to glycoproteins and glycolipids. The isolectin Griffonia simplicifolia I-B4 (IB4) recognizes terminal alpha-galactose and binds to a subset of small and medium-sized neurons in the dorsal root ganglia (DRG). Using one and two-dimensional gel electrophoresis, we have identified several proteins that bind IB4 in sciatic nerve, dorsal horn, and DRG. Treatment with the enzyme alpha-galactosidase reduces IB4 binding, strongly suggesting the binding is specific for the IB4 epitope. Mass spectrometric analysis of tryptic digests of alpha-galactosidase sensitive bands identified three proteins that bind IB4: the laminin beta 2 chain and the light and medium subunits of neurofilaments.

  1. Direct injection into the dorsal root ganglion: technical, behavioral, and histological observations.

    Science.gov (United States)

    Fischer, Gregory; Kostic, Sandra; Nakai, Hiroyuki; Park, Frank; Sapunar, Damir; Yu, Hongwei; Hogan, Quinn

    2011-07-15

    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 μl of dye injected through a pulled glass pipette directly into the distal DRG, exposed by a minimal foraminotomy, produces complete filling of the DRG with limited extension into the spinal roots. Injection into the spinal nerve required 3 μl to achieve comparable DRG filling, produced preferential spread into the ventral root, and was accompanied by substantial leakage of injected solution from the injection site. Injections into the sciatic nerve of volumes up to 10 μl did not reach the DRG. Transient hypersensitivity to mechanical stimulation at threshold (von Frey) and noxious levels (pin) developed after 2 μl saline injection directly into the DRG that was in part attributable to the surgical exposure procedure alone. Only minimal astrocyte activation in the spinal dorsal horn was evident after DRG saline injections. Injection of adeno-associated virus (AAV) vector conveying green fluorescent protein (GFP) transgene resulted in expression as soon as 1 day after injection into the DRG, including fibers in the spinal dorsal horn and columns. AAV injection into the DRG produced additional thermal hypersensitivity and withdrawal from the stroke of a brush and compromised motor performance. These findings demonstrate a method for selective injection of agents into single DRGs for anatomically restricted actions. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. HeyL Regulates the Number of TrkC Neurons in Dorsal Root Ganglia

    OpenAIRE

    Mukhopadhyay, Abhishek; Jarrett, Jennifer; Chlon, Timothy; Kessler, John A

    2009-01-01

    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 neuronal specification. Homozygous null mutation of HeyL reduced the number of TrkC+ neurons in DRG at birth including the subpopulation that expresse...

  3. Distribution pattern of dorsal root ganglion neurons synthesizing nitric oxide synthase in different animal species.

    Science.gov (United States)

    Kolesár, Dalibor; Kolesárová, Mária; Kyselovič, Ján

    2017-04-01

    The main aim of the present review is to provide at first a short survey of the basic anatomical description of sensory ganglion neurons in relation to cell size, conduction velocity, thickness of myelin sheath, and functional classification of their processes. In addition, we have focused on discussing current knowledge about the distribution pattern of neuronal nitric oxide synthase containing sensory neurons especially in the dorsal root ganglia in different animal species; hence, there is a large controversy in relation to interpretation of the results dealing with this interesting field of research.

  4. Molecular target size of the vanilloid (capsaicin) receptor in pig dorsal root ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Szallasi, A.; Blumberg, P.M. (National Cancer Institute, Bethesda, MD (USA))

    1991-01-01

    The size of the vanilloid receptor was examined by high-energy radiation inactivation analysis of the binding of ({sup 3}H)resiniferatoxin to pig dorsal root ganglion membranes; it was found to be 270 {plus minus} 25 kDa. This value most likely represents the size of a receptor complex rather than of an individual subunit. Other ligand-gated cation channel complexes have reported molecular weights in this range, e.g. 300 kDa for the acetylcholine receptor.

  5. Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine

    Directory of Open Access Journals (Sweden)

    Aoki Junken

    2010-11-01

    Full Text Available Abstract Background Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1 signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/- mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-, which converts lysophosphatidylcholine (LPC to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice. Conclusions These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain.

  6. Systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of alpha 2 adrenergic receptor subtypes A, B and C in dorsal root ganglion and dorsal horn.

    Science.gov (United States)

    Tamagaki, Shinji; Suzuki, Takahiro; Hagihira, Satoshi; Hayashi, Yukio; Mashimo, Takashi

    2010-12-01

     It has been reported that the effect of intrathecally administered α2 adrenergic receptor (α2 AR) agonists is enhanced in mice that are chronically tolerant to systemic morphine. However, contributory factors have not been identified. Here we examined whether repeated systemic morphine affected the analgesic potency of intrathecal dexmedetomidine and the expression of subtype A, B and C α2 AR (α2A, α2B and α2C AR) in the dorsal root ganglion and dorsal horn in mice. After subcutaneous injection of morphine or saline for two weeks, dexmedetomidine was administered intrathecally to evaluate its antinociceptive effect. Also, the α2 AR subtypes and µ-opioid receptor mRNA expression in lumbar dorsal root ganglion was quantified using PCR, and α2A and α2C AR in lumbar dorsal root ganglion and dorsal horn were examined by immunohistochemistry. Daily morphine enhanced the antinociceptive effect of intrathecal dexmedetomidine, increased all the α2 AR subtypes but decreased the µ-opioid receptor mRNA expression in dorsal root ganglion and increased immunoreactivity of α2A and α2C AR in dorsal root ganglion and dorsal horn. These results suggest that systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of the α2A, α2B and α2C AR in lumbar dorsal root ganglion and dorsal horn. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.

  7. A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord

    DEFF Research Database (Denmark)

    Hoeber, Jan; Konig, Niclas; Trolle, Carl

    2017-01-01

    Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly...... restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (Meso......MIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of Meso...

  8. Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Blum, E. [Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240 (Israel); Procacci, P.; Conte, V.; Sartori, P. [Dipartimento di Scienze Biomediche per la Salute, University of Milan, via Mangiagalli 14, I-20133 Milano (Italy); Hanani, M., E-mail: hananim@cc.huji.ac.il [Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240 (Israel)

    2017-01-01

    Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopy was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injection exerts long-term behavioral and cellular changes. The results are consistent with the idea that SGC activation contributes to hyperalgesia. - Highlights: • A single lipopolysaccharides injection activated glia in mouse dorsal root ganglia for 30 days. • This was accompanied by increased communications by gap junctions among glia and by hyperalgesia. • Glial activation and coupling may contribute to chronic pain.

  9. Satellite glial cells in dorsal root ganglia are activated in streptozotocin-treated rodents.

    Science.gov (United States)

    Hanani, Menachem; Blum, Erez; Liu, Shuangmei; Peng, Lichao; Liang, Shangdong

    2014-12-01

    Neuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pain types, and we investigated what are the changes that satellite glial cells (SGCs) in dorsal root ganglia undergo in a DM type 1 model, induced by streptozotocin (STZ) in mice and rats. We carried out immunohistochemical studies to learn about changes in the activation marker glial fibrillary acidic protein (GFAP) in SGCs. We found that after STZ-treatment the number of neurons surrounded with GFAP-positive SGCs in dorsal root ganglia increased 4-fold in mice and 5-fold in rats. Western blotting for GFAP, which was done only on rats because of the larger size of the ganglia, showed an increase of about 2-fold in STZ-treated rats, supporting the immunohistochemical results. These results indicate for the first time that SGCs are activated in rodent models of DM1. As SGC activation appears to contribute to chronic pain, these results suggest that SGCs may participate in the generation and maintenance of diabetic neuropathic pain, and can serve as a potential therapeutic target. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. Highly efficient method for gene delivery into mouse dorsal root ganglia neurons.

    Science.gov (United States)

    Yu, Lingli; Reynaud, Florie; Falk, Julien; Spencer, Ambre; Ding, Yin-Di; Baumlé, Véronique; Lu, Ruisheng; Castellani, Valérie; Yuan, Chonggang; Rudkin, Brian B

    2015-01-01

    The development of gene transfection technologies has greatly advanced our understanding of life sciences. While use of viral vectors has clear efficacy, it requires specific expertise and biological containment conditions. Electroporation has become an effective and commonly used method for introducing DNA into neurons and in intact brain tissue. The present study describes the use of the Neon® electroporation system to transfect genes into dorsal root ganglia neurons isolated from embryonic mouse Day 13.5-16. This cell type has been particularly recalcitrant and refractory to physical or chemical methods for introduction of DNA. By optimizing the culture condition and parameters including voltage and duration for this specific electroporation system, high efficiency (60-80%) and low toxicity (>60% survival) were achieved with robust differentiation in response to Nerve growth factor (NGF). Moreover, 3-50 times fewer cells are needed (6 × 10(4)) compared with other traditional electroporation methods. This approach underlines the efficacy of this type of electroporation, particularly when only limited amount of cells can be obtained, and is expected to greatly facilitate the study of gene function in dorsal root ganglia neuron cultures.

  11. Highly efficient method for gene delivery in mouse dorsal root ganglia neurons

    Directory of Open Access Journals (Sweden)

    Lingli eYu

    2015-02-01

    Full Text Available The development of gene transfection technologies has greatly advanced our understanding of life sciences. While use of viral vectors has clear efficacy, it requires specific expertise and biological containment conditions. Electroporation has become an effective and commonly used method for introducing DNA into neurons and in intact brain tissue. The present study describes the use of the Neon® electroporation system to transfect genes into dorsal root ganglia neurons isolated from embryonic mouse Day 13.5 to 16. This cell type has been particularly recalcitrant and refractory to physical or chemical methods for introduction of DNA. By optimizing the culture condition and parameters including voltage and duration for this specific electroporation system, high efficiency (60 – 80% and low toxicity (> 60% survival were achieved with robust differentiation in response to Nerve growth factor (NGF. Moreover, 3-50 times fewer cells are needed (6x104 compared with other traditional electroporation methods. This approach underlines the efficacy of this type of electroporation, particularly when only limited amount of cells can be obtained, and is expected to greatly facilitate the study of gene function in dorsal root ganglia neuron cultures.

  12. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    Science.gov (United States)

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy.

  13. Sustained FXN expression in dorsal root ganglia from a nonreplicative genomic HSV-1 vector.

    Science.gov (United States)

    Ventosa, Maria; Wu, Zetang; Lim, Filip

    2017-11-01

    Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disease caused by mutations in the frataxin gene (FXN), which lead to reduced levels of the essential mitochondrial protein frataxin. Currently, there is no effective cure. With the aim of developing a gene therapy for FA neuropathology, we describe the construction and preliminary characterization of a high-capacity nonreplicative genomic herpes simplex virus type 1 vector (H24B-FXNlac vector) carrying a reduced version of the human FXN genomic locus, comprising the 5-kb promoter and the FXN cDNA with the inclusion of intron 1. We show that the transgene cassette contains the elements necessary to preserve physiological neuronal regulation of human FXN expression. Transduction of cultured fetal rat dorsal root ganglia neurons with the H24B-FXNlac vector results in sustained expression of human FXN transcripts and frataxin protein. Rat footpad inoculation with the H24B-FXNlac vector results in human FXN transgene delivery to the dorsal root ganglia, with expression persisting for at least 1 month. The results of the present study support the feasibility of using this vector for sustained neuronal expression of human frataxin for FA gene therapy. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Calcium activity of upper thoracic dorsal root ganglion neurons in zucker diabetic Fatty rats

    DEFF Research Database (Denmark)

    Ghorbani, Marie Louise; Nyborg, Niels C B; Fjalland, Bjarne

    2013-01-01

    or in combination with algogenic chemicals (bradykinin, serotonin, prostaglandin E2 (all 10(-5)¿M), and adenosine (10(-3)¿M)) at pH 7.4 and 6.0. Neurons from diabetic animals exhibited an overall increased response to stimulation with 20¿mM¿K(+) compared to neurons from control. Stimulation with Capsaicin alone...... caused an augmented response in neurons from diabetic animals compared to control animals. When stimulated with a combination of Capsaicin and algogenic chemicals, no differences between the two groups of neurons were measured, neither at pH 7.4 nor 6.0. In conclusion, diabetes-induced alterations......The aim of the present study was to examine the calcium activity of C8-T5 dorsal root ganglion (DRG) neurons from Zucker diabetic fatty rats. In total, 8 diabetic ZDF fatty animals and 8 age-matched control ZDF lean rats were employed in the study. C8-T5 dorsal root ganglia were isolated...

  15. Electrophysiologic changes in dorsal root ganglion neurons and behavioral changes in a lumbar radiculopathy model.

    Science.gov (United States)

    Kirita, Takashi; Takebayashi, Tsuneo; Mizuno, Satoshi; Takeuchi, Hirohito; Kobayashi, Takeshi; Fukao, Mitsuhiro; Yamashita, Toshihiko; Tohse, Noritsugu

    2007-01-15

    The DRG neuron was electrophysiologically investigated using a rat model with constriction of the proximal site of the DRG. To investigate the pathomechanisms of lumbar radiculopathy, we established a rat model with constriction of the proximal site of the DRG. And to characterize the DRG neurons in the rat model of lumbar radiculopathy, the physiologic properties regarding action potential, Na, and K current of the DRG neurons were analyzed through the use of patch clamp recordings. In lumbar root constriction models, properties of secondary afferent neurons in the dorsal horn have been investigated. However, the electrical properties of DRG neuron have not been well investigated. To compare the excitability of DRG neurons between root constriction models and sham, we examined the threshold current, action potential (AP) threshold, resting membrane potential (RMP), afterhyperpolarization (AHP), action potential duration 50 (APD50), action potential amplitude, maximum rise time of AP, and pattern of discharges evoked by depolarizing current. We also examined the peak Na current and steady-state Na and K currents with the voltage clamp technique. The rats in the root constriction group demonstrated mechanical allodynia and thermal hyperalgesia. In measurement of the action potential, lower threshold current, more depolarized RMP, larger AHP, and prolonged APD50 were measured in the root constriction neurons compared with the sham group. The incidence of sustained burst was significantly higher in root constriction neurons. The Na current in root constriction neurons was markedly larger. There were no significant differences in K current density and voltage dependency. The constriction of lumbar root increased excitability and Na current amplitude of DRG neurons. These findings indicate that lumbar radicular pain may be associated with increased excitability of involved DRG neurons.

  16. A compact dual promoter adeno-associated viral vector for efficient delivery of two genes to dorsal root ganglion neurons

    NARCIS (Netherlands)

    Fagoe, N D; Eggers, R; Verhaagen, J; Mason, M R J

    Adeno-associated viral (AAV) vectors based on serotype 5 are an efficient means to target dorsal root ganglia (DRG) to study gene function in the primary sensory neurons of the peripheral nervous system. In this study, we have developed a compact AAV dual promoter vector composed of the

  17. Homeobox gene expression in adult dorsal root ganglia during sciatic nerve regeneration: is regeneration a recapitulation of development?

    NARCIS (Netherlands)

    Gispen, W.H.; Vogelaar, C.F.; Hoekman, M.F.; Burbach, J.P.H.

    2003-01-01

    After damage of the sciatic nerve, a regeneration process is initiated. Neurons in the dorsal root ganglion regrow their axons and functional connections. The molecular mechanisms of this neuronal regenerative process have remained elusive, but a relationship with developmental processes has been

  18. Neuroimmune and Neuropathic Responses of Spinal Cord and Dorsal Root Ganglia in Middle Age.

    Science.gov (United States)

    Galbavy, William; Kaczocha, Martin; Puopolo, Michelino; Liu, Lixin; Rebecchi, Mario J

    2015-01-01

    Prior studies of aging and neuropathic injury have focused on senescent animals compared to young adults, while changes in middle age, particularly in the dorsal root ganglia (DRG), have remained largely unexplored. 14 neuroimmune mRNA markers, previously associated with peripheral nerve injury, were measured in multiplex assays of lumbar spinal cord (LSC), and DRG from young and middle-aged (3, 17 month) naïve rats, or from rats subjected to chronic constriction injury (CCI) of the sciatic nerve (after 7 days), or from aged-matched sham controls. Results showed that CD2, CD3e, CD68, CD45, TNF-α, IL6, CCL2, ATF3 and TGFβ1 mRNA levels were substantially elevated in LSC from naïve middle-aged animals compared to young adults. Similarly, LSC samples from older sham animals showed increased levels of T-cell and microglial/macrophage markers. CCI induced further increases in CCL2, and IL6, and elevated ATF3 mRNA levels in LSC of young and middle-aged adults. Immunofluorescence images of dorsal horn microglia from middle-aged naïve or sham rats were typically hypertrophic with mostly thickened, de-ramified processes, similar to microglia following CCI. Unlike the spinal cord, marker expression profiles in naïve DRG were unchanged across age (except increased ATF3); whereas, levels of GFAP protein, localized to satellite glia, were highly elevated in middle age, but independent of nerve injury. Most neuroimmune markers were elevated in DRG following CCI in young adults, yet middle-aged animals showed little response to injury. No age-related changes in nociception (heat, cold, mechanical) were observed in naïve adults, or at days 3 or 7 post-CCI. The patterns of marker expression and microglial morphologies in healthy middle age are consistent with development of a para-inflammatory state involving microglial activation and T-cell marker elevation in the dorsal horn, and neuronal stress and satellite cell activation in the DRG. These changes, however, did not

  19. Neuroimmune and Neuropathic Responses of Spinal Cord and Dorsal Root Ganglia in Middle Age.

    Directory of Open Access Journals (Sweden)

    William Galbavy

    Full Text Available Prior studies of aging and neuropathic injury have focused on senescent animals compared to young adults, while changes in middle age, particularly in the dorsal root ganglia (DRG, have remained largely unexplored. 14 neuroimmune mRNA markers, previously associated with peripheral nerve injury, were measured in multiplex assays of lumbar spinal cord (LSC, and DRG from young and middle-aged (3, 17 month naïve rats, or from rats subjected to chronic constriction injury (CCI of the sciatic nerve (after 7 days, or from aged-matched sham controls. Results showed that CD2, CD3e, CD68, CD45, TNF-α, IL6, CCL2, ATF3 and TGFβ1 mRNA levels were substantially elevated in LSC from naïve middle-aged animals compared to young adults. Similarly, LSC samples from older sham animals showed increased levels of T-cell and microglial/macrophage markers. CCI induced further increases in CCL2, and IL6, and elevated ATF3 mRNA levels in LSC of young and middle-aged adults. Immunofluorescence images of dorsal horn microglia from middle-aged naïve or sham rats were typically hypertrophic with mostly thickened, de-ramified processes, similar to microglia following CCI. Unlike the spinal cord, marker expression profiles in naïve DRG were unchanged across age (except increased ATF3; whereas, levels of GFAP protein, localized to satellite glia, were highly elevated in middle age, but independent of nerve injury. Most neuroimmune markers were elevated in DRG following CCI in young adults, yet middle-aged animals showed little response to injury. No age-related changes in nociception (heat, cold, mechanical were observed in naïve adults, or at days 3 or 7 post-CCI. The patterns of marker expression and microglial morphologies in healthy middle age are consistent with development of a para-inflammatory state involving microglial activation and T-cell marker elevation in the dorsal horn, and neuronal stress and satellite cell activation in the DRG. These changes, however

  20. Synaptic plasticity and sensory-motor improvement following fibrin sealant dorsal root reimplantation and mononuclear cell therapy

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    Suzana Ulian Benitez

    2014-09-01

    Full Text Available Root lesions may affect both dorsal and ventral roots. However, due to the possibility of generating further inflammation and neuropathic pain, surgical procedures do not prioritize the repair of the afferent component. The loss of such sensorial input directly disturbs the spinal circuits thus affecting the functionality of the injuried limb. The present study evaluated the motor and sensory improvement following dorsal root reimplantation with fibrin sealant (FS plus bone marrow mononuclear cells (MC after dorsal rhizotomy. MC were used to enhance the repair process. We also analyzed changes in the glial response and synaptic circuits within the spinal cord. Female Lewis rats (6-8 weeks old were divided in three groups: rhizotomy (RZ group, rhizotomy repaired with FS (RZ+FS group and rhizotomy repaired with FS and MC (RZ+FS+MC group. The behavioral tests electronic von-Frey and Walking track test were carried out. For immunohistochemistry we used markers to detect different synapse profiles as well as glial reaction. The behavioral results showed a significant decrease in sensory and motor function after lesion. The reimplantation decreased glial reaction and improved synaptic plasticity of afferent inputs. Cell therapy further enhanced the rewiring process. In addition, both reimplanted groups presented twice as much motor control compared to the non-treated group. In conclusion, the reimplantation with FS and MC is efficient and may be considered an approach to improve sensory-motor recovery following dorsal rhizotomy.

  1. Pulsed Radiofrequency to the Dorsal Root Ganglion in Acute Herpes Zoster and Postherpetic Neuralgia.

    Science.gov (United States)

    Kim, Koohyun; Jo, Daehyun; Kim, EungDon

    2017-03-01

    Latent varicella zoster virus reactivates mainly in sensory ganglia such as the dorsal root ganglion (DRG) or trigeminal ganglion. The DRG contains many receptor channels and is an important region for pain signal transduction. Sustained abnormal electrical activity to the spinal cord via the DRG in acute herpes zoster can result in neuropathic conditions such as postherpetic neuralgia (PHN). Although the efficacy of pulsed radiofrequency (PRF) application to the DRG in various pain conditions has been previously reported, the application of PRF to the DRG in patients with herpes zoster has not yet been studied. The aim of the present study was to compare the clinical effects of PRF to the DRG in patients with herpes zoster to those of PRF to the DRG in patients with PHN. Retrospective comparative study. University hospital pain center in Korea. The medical records of 58 patients who underwent PRF to the DRG due to zoster related pain (herpes zoster or PHN) were retrospectively analyzed. Patients were divided into 2 groups according to the timing of PRF after zoster onset: an early PRF group (within 90 days) and a PHN PRF group (more than 90 days). The efficacy of PRF was assessed by a numeric rating scale (NRS) and by recording patient medication doses before PRF and at one week, 4 weeks, 8 weeks, and 12 weeks after PRF. Pain intensity was decreased after PRF in all participants. However, the degree of pain reduction was significantly higher in the early PRF group. Moreover, more patients discontinued their medication in the early PRF group, and the PRF success rate was also higher in the early PRF group. The relatively small sample size from a single center, short duration of review of medical records, and the retrospective nature of the study. PRF to the DRG is a useful treatment for treatment-resistant cases of herpes zoster and PHN. Particularly in herpes zoster patients with intractable pain, application of PRF to the DRG should be considered for pain control

  2. [Effect of triptolide on iNOS and SP expressions in spinal dorsal horn and dorsal root ganglion of rats with adjuvant arthritis].

    Science.gov (United States)

    Chen, Wei; Zhang, Xu-Dong; Lu, Zhuo-Hui; Wei, Deng-Ming

    2014-05-01

    To observe the analgesic effect of triptolide (TP) of high, middle and low doses on rats with adjuvant arthritis (AA), and the expressions of inducible nitric oxide synthase (iNOS) and substance P (SP) in spinal dorsal horn and dorsal root ganglion (DRG) of corresponding sections, in order to discuss the possible mechanism for the analgesic effect of TP on rats with adjuvant arthritis. Fifty SD rats were selected and randomly divided into the normal group (group A), the model group (group B), and TP low (group C), middle (group D), high (group E) dose groups. Except for the group A, all of the remaining groups were injected with 0.1 mL of Freund's complete adjuvant through their right rear toes to establish the model. At 14 d after the model establishment, rats in C, D and E groups were intraperitoneally injected with different doses of TP (0.1 mg x kg(-1) for the group C, 0.2 mg x kg(-1) for the group D, 0.4 mg x kg(-1) for the group E) once a day for 9 days. Then the 50% mechanical withdraw threshold (MWT) was determined. And the expressions of iNOS and SP in lumbar5 (L5) spinal dorsal horn and DRG were detected with the immunohistochemical method. The 50% MWT of rats in the group B was significantly lower than that of the group A (P effect relationship. The immunohistochemical results indicated that the iNOS and SP expressions significantly increased in the group B (P effect relationship. TP shows a good analgesic effect on AA, and could inhibit the iNOS and SP expressions in spinal dorsal horn and DRG in rats with adjuvant arthritis, which may be one of action mechanisms for the analgesic effect of TP.

  3. A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord.

    Science.gov (United States)

    Hoeber, Jan; König, Niclas; Trolle, Carl; Lekholm, Emilia; Zhou, Chunfang; Pankratova, Stanislava; Åkesson, Elisabet; Fredriksson, Robert; Aldskogius, Håkan; Kozlova, Elena N

    2017-07-15

    Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along "bridges" formed by migrating stem cells. Coimplantation of MesoMIM prevented stem cell migration, "bridges" were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular "bridges" in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient alternative way to induce sensory axon regeneration, and (3) a combinatorial approach of individually beneficial components is not necessarily additive, but can be counterproductive for axonal growth.

  4. Effects of free fatty acids on sodium currents in rat dorsal root ganglion neurons.

    Science.gov (United States)

    Hong, Min-Pyo; Kim, Hong Im; Shin, Yong Kyoo; Lee, Chung Soo; Park, Mijung; Song, Jin-Ho

    2004-05-15

    Free fatty acids (FFAs), especially polyunsaturated fatty acids (PUFAs), are potent modulators of muscle-type sodium channels. It is not known if they also modulate sodium channels of sensory neurons. In this study, we investigated the effects of FFAs on the fast tetrodotoxin-sensitive (fTTX-S) and the slow tetrodotoxin-resistant (sTTX-R) sodium currents in rat dorsal root ganglion neurons. At a holding potential of -80 mV, PUFAs potently inhibited fTTX-S current, but monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs) to a lesser extent. All FFAs initially increased sTTX-R current, and then decreased it slightly. PUFAs and MUFAs produced a hyperpolarizing shift of the steady-state inactivation voltage for both types of sodium currents. The shift generally increased with the number of unsaturated bonds. FFAs did not change the maximum amplitude of fTTX-S current, but increased that of sTTX-R current. Most FFAs shifted the activation voltage for fTTX-S current in the hyperpolarizing direction, which was not dependent on the degree of unsaturation. MUFAs and SFAs shifted the activation voltage for sTTX-R current in the hyperpolarizing direction, but PUFAs were without effect. The modulation of sodium currents by FFAs, especially PUFAs, may have considerable impact on the excitability of sensory neurons.

  5. The role of the transcription factor Rbpj in the development of dorsal root ganglia

    Directory of Open Access Journals (Sweden)

    Chen Jia-Yin

    2011-04-01

    Full Text Available Abstract Background The 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 scope of Notch functions in mammalian DRG development remains poorly understood. Results In the present study, we used Wnt1-Cre to conditionally inactivate the transcription factor Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells. Deletion of Rbpj caused the up-regulation of NeuroD1 and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell death. In addition, gliogenesis was delayed initially, but a near-complete loss of glia was observed finally in Rbpj-deficient DRG. Furthermore, we found P75 and Sox10, which are normally expressed exclusively in neuronal and glial progenitors of the DRG after the NCCs have completed their migration, were co-expressed in many cells of the DRG of Rbpj conditional knock-out mice. Conclusions Our data indicate that Rbpj-mediated canonical Notch signaling inhibits DRG neuronal differentiation, possibly by regulating NeuroD1 expression, and is required for DRG gliogenesis in vivo.

  6. Postembryonic neuronal addition in Zebrafish dorsal root ganglia is regulated by Notch signaling

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    McGraw Hillary

    2012-06-01

    Full Text Available Abstract Background The sensory neurons and glia of the dorsal root ganglia (DRG arise from neural crest cells in the developing vertebrate embryo. In mouse and chick, DRG formation is completed during embryogenesis. In contrast, zebrafish continue to add neurons and glia to the DRG into adulthood, long after neural crest migration is complete. The molecular and cellular regulation of late DRG growth in the zebrafish remains to be characterized. Results In the present study, we use transgenic zebrafish lines to examine neuronal addition during postembryonic DRG growth. Neuronal addition is continuous over the period of larval development. Fate-mapping experiments support the hypothesis that new neurons are added from a population of resident, neural crest-derived progenitor cells. Conditional inhibition of Notch signaling was used to assess the role of this signaling pathway in neuronal addition. An increase in the number of DRG neurons is seen when Notch signaling is inhibited during both early and late larval development. Conclusions Postembryonic growth of the zebrafish DRG comes about, in part, by addition of new neurons from a resident progenitor population, a process regulated by Notch signaling.

  7. Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia.

    Science.gov (United States)

    Zhang, X; Chen, Y; Wang, C; Huang, L-Y M

    2007-06-05

    It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca(2+) entry is required for the release. FM1-43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca(2+) channels completely eliminates the neuron-glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-alpha (TNFalpha) from satellite cells. TNFalpha in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell-cell signaling.

  8. Tlx3 Function in the Dorsal Root Ganglion is Pivotal to Itch and Pain Sensations

    Directory of Open Access Journals (Sweden)

    Chengcheng Huang

    2017-06-01

    Full Text Available Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG. As a result, Tlx3F/F;Nav1.8-cre mice exhibit significantly attenuated acute and dry skin-induced chronic itch. Furthermore, our study indicates that TRPV1 plays a pivotal role in the chronic itch evoked by dry skin and allergic contact dermatitis (ACD. The mutants also display impaired response to cold and inflammatory pain and elevated response to capsaicin, whereas the responses to acute mechanical, thermal stimuli and neuropathic pain remain normal. In Tlx3F/F;Nav1.8-cre mice, TRPV1 is derepressed and expands predominantly into IB4+ non-peptidergic (NP neurons. Collectively, our data reveal a molecular mechanism in regulating the development of pruriceptors and controlling itch and pain sensations.

  9. Sialic acid contributes to hyperexcitability of dorsal root ganglion neurons in rats with peripheral nerve injury.

    Science.gov (United States)

    Peng, Xiao-Qing; Zhang, Xiu-Lin; Fang, Yan; Xie, Wen-Rui; Xie, Yi-Kuan

    2004-11-12

    Axonal injury of the dorsal root ganglion (DRG) neurons may alter the synthesis of certain membrane proteins that are responsible for the development of abnormal hyperexcitability. The external domains of most of these membrane proteins are sialylated. Because sialic acid carries heavy negative charges, the increase of sialylated proteins may increase neurons' negative surface charges, which will have predictable effects on the voltage-gated channels, and affect the excitability of injured neurons. Using intracellular electrophysiological recording, we demonstrated that following chronic constriction injury (CCI) of the sciatic nerve, Aalpha/beta DRG neurons become hyperexcitable, as indicated by a more depolarized resting membrane potential (Vm) and a lowered threshold current (TIC). More interestingly, the excitability of injured DRG neurons was reduced substantially when the extracellular sialic acid was removed by pretreatment with neuraminidase. The Vm was less depolarized and the TIC increased robustly as compared to the CCI neurons without neuraminidase treatment. However, desialylation of normal, intact neurons had no significant effect on the Vm and less effect on the TIC. Our results suggest that the hyperexcitability of injured sensory neurons may be associated with increased negatively charged sialic acid residues on the surface of the neuronal somata.

  10. Roles of syndecan-4 and relative kinases in dorsal root ganglion neuron adhesion and mechanotransduction.

    Science.gov (United States)

    Lin, Tzu-Jou; Lu, Kung-Wen; Chen, Wei-Hsin; Cheng, Chao-Min; Lin, Yi-Wen

    2015-04-10

    Mechanical stimuli elicit a biological response and initiate complex physiological processes, including neural feedback schemes associated with senses such as pain, vibration, touch, and hearing. The syndecans (SDCs), a group of adhesion receptors, can modulate adhesion and organize the extracellular matrix (ECM). In this study, we cultured dorsal root ganglia (DRG) on controlled polydimethylsiloxane (PDMS) substrates coated with poly-l-lysine (poly) or fibronectin (FN) to investigate cell adhesion and mechanotransduction mechanisms by mechanical stretching on PDMS using DRG neurons. Our results demonstrated that neuronal density, neurite length, and neurite branching were lower in the PDMS group and could be further reversed through activating SDC-4 by FN. The expression of the SDC-4 pathway decreased but with increased pPKCα in the PDMS-poly group. After mechanical stretching, pPKCα-FAKpTyr397-pERK1/2 expression was increased in both poly- and FN-coated PDMS. These results indicate that SDC4-pPKCα-FAKpTyr397-pERK1/2 may play a crucial role in DRG adhesion and mechanotransduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Orexin affects dorsal root ganglion neurons: a mechanism for regulating the spinal nociceptive processing.

    Science.gov (United States)

    Yan, J-A; Ge, L; Huang, W; Song, B; Chen, X-W; Yu, Z-P

    2008-01-01

    Orexins (orexin A and B) are initially known to be a hypothalamic peptide critical for feeding and normal wakefulness. In addition, emerging evidence from behavioral tests suggests that orexins are also involved in the regulation of nociceptive processing, suggesting a novel potential therapeutic approach for pain treatment. Both spinal and supraspinal mechanisms appear to contribute to the role of orexin in nociception. In the spinal cord, dorsal root ganglion (DRG) neurons are primary afferent neurons that transmit peripheral stimuli to the pain-processing areas. Morphological results show that both orexin A and orexin-1 receptor are distributed in DRG neurons. Moreover, by using whole-cell patch-clamp recordings and calcium imaging measurements we found that orexin A induced excitability and intracellular calcium concentration elevation in the isolated rat DRG neurons, which was mainly dependent on the activation of spinal orexin-1 receptor. Based on these findings, we propose a hypothesis that the direct effect of orexin A on DRG neurons would represent a possible mechanism for the orexinergic modulation of spinal nociceptive transmission.

  12. Cervical Spinal Cord and Dorsal Nerve Root Stimulation for Neuropathic Upper Limb Pain.

    Science.gov (United States)

    Levine, Adrian B; Parrent, Andrew G; MacDougall, Keith W

    2017-01-01

    Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain in the lower limbs. Upper limb pain comprises a significant proportion of neuropathic pain patients, but is often difficult to target specifically and consistently with paresthesias. We hypothesized that the use of dorsal nerve root stimulation (DNRS), as an option along with SCS, would help us better relieve pain in these patients. All 35 patients trialed with spinal stimulation for upper limb pain between July 1, 2011, and October 31, 2013, were included. We performed permanent implantation in 23/35 patients based on a visual analogue scale pain score decrease of ≥50% during trial stimulation. Both the SCS and DNRS groups had significant improvements in average visual analogue scale pain scores at 12 months compared with baseline, and the majority of patients in both groups obtained ≥50% pain relief. The majority of patients in both groups were able to reduce their opioid use, and on average had improvements in Short Form-36 quality of life scores. Complication rates did not differ significantly between the two groups. Treatment with SCS or DNRS provides meaningful long-term relief of chronic neuropathic pain in the upper limbs.

  13. CaMK II γ down regulation protects dorsal root ganglion neurons from ropivacaine hydrochloride neurotoxicity.

    Science.gov (United States)

    Wen, Xian-Jie; Li, Xiao-Hong; Li, Heng; Liang, Hua; Yang, Chen-Xiang; Wang, Han-Bing

    2017-07-12

    T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h. Cell viability, apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, and Cav3.3 expression were detected. Ultrastructural changes in DRG were observed under a transmission electron microscope. The results demonstrated that the cell viability of DRG treated with ropivacaine hydrochloride decreased markedly, the apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, Cav3.3 expression increased significantly. CaMKIIγ up-regulation aggravated ropivacaine hydrochloride-induced cell damage and increased Cav3.2 and Cav3.3 expression. In conclusion, CaMKIIγ regulated Cav3.2 and Cav3.3 expression in DRG, which was involved with ropivacaine hydrochloride-induced cell injury.

  14. Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain.

    Science.gov (United States)

    Berta, Temugin; Qadri, Yawar; Tan, Ping-Heng; Ji, Ru-Rong

    2017-07-01

    Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered: The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons. These changes result in hypersensitivity and hyperexcitability of sensory neurons (peripheral sensitization) and are crucial for the onset and maintenance of chronic pain. We discuss the following new strategies to target DRGs and primary sensory neurons as a means of alleviating chronic pain and minimizing side effects: inhibition of sensory neuron-expressing ion channels such as TRPA1, TRPV1, and Nav1.7, selective blockade of C- and Aβ-afferent fibers, gene therapy, and implantation of bone marrow stem cells. Expert opinion: These peripheral pharmacological treatments, as well as gene and cell therapies, aimed at DRG tissues and primary sensory neurons can offer better and safer treatments for inflammatory, neuropathic, cancer, and other chronic pain states.

  15. Global analysis of transcriptome in dorsal root ganglia following peripheral nerve injury in rats.

    Science.gov (United States)

    Gong, Leilei; Wu, Jiancheng; Zhou, Songlin; Wang, Yaxian; Qin, Jing; Yu, Bin; Gu, Xiaosong; Yao, Chun

    2016-09-09

    Peripheral nervous system has intrinsic regeneration ability after injury, accompanied with the coordination of numerous cells, molecules and signaling pathways. These post-injury biological changes are complex with insufficient understanding. Thus, to obtain a global perspective of changes following nerve injury and to elucidate the mechanisms underlying nerve regeneration are of great importance. By RNA sequencing, we detected transcriptional changes in dorsal root ganglia (DRG) neurons at 0 h, 3 h, 9 h, 1 d, 4 d and 7 d following sciatic nerve crush injury in rats. Differentially expressed genes were then selected and classified into major clusters according to their expression patterns. Cluster 2 (with genes high expressed before 9 h and then down expressed) and cluster 6 (combination of cluster 4 and 5 with genes low expressed before 1 d and then up expressed) were underwent GO annotation and KEGG pathway analysis. Gene act networks were then constructed for these two clusters and the expression of pivotal genes was validated by quantitative real-time PCR. This study provided valuable information regarding the transcriptome changes in DRG neurons following nerve injury, identified potential genes that could be used for improving axon regeneration after nerve injury, and facilitated to elucidate the biological process and molecular mechanisms underlying peripheral nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Differential transcriptional profiling of damaged and intact adjacent dorsal root ganglia neurons in neuropathic pain.

    Directory of Open Access Journals (Sweden)

    A K Reinhold

    Full Text Available Neuropathic pain, caused by a lesion in the somatosensory system, is a severely impairing mostly chronic disease. While its underlying molecular mechanisms are not thoroughly understood, neuroimmune interactions as well as changes in the pain pathway such as sensitization of nociceptors have been implicated. It has been shown that not only are different cell types involved in generation and maintenance of neuropathic pain, like neurons, immune and glial cells, but, also, intact adjacent neurons are relevant to the process. Here, we describe an experimental approach to discriminate damaged from intact adjacent neurons in the same dorsal root ganglion (DRG using differential fluorescent neuronal labelling and fluorescence-activated cell sorting (FACS. Two fluorescent tracers, Fluoroemerald (FE and 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI, were used, whose properties allow us to distinguish between damaged and intact neurons. Subsequent sorting permitted transcriptional analysis of both groups. Results and qPCR validation show a strong regulation in damaged neurons versus contralateral controls as well as a moderate regulation in adjacent neurons. Data for damaged neurons reveal an mRNA expression pattern consistent with established upregulated genes like galanin, which supports our approach. Moreover, novel genes were found strongly regulated such as corticotropin-releasing hormone (CRH, providing novel targets for further research. Differential fluorescent neuronal labelling and sorting allows for a clear distinction between primarily damaged neuropathic neurons and "bystanders," thereby facilitating a more detailed understanding of their respective roles in neuropathic processes in the DRG.

  17. Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

    Science.gov (United States)

    Khurram, Abeer; Ross, Shani E.; Sperry, Zachariah J.; Ouyang, Aileen; Stephan, Christopher; Jiman, Ahmad A.; Bruns, Tim M.

    2017-06-01

    Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

  18. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors.

    Directory of Open Access Journals (Sweden)

    Caroline Flegel

    Full Text Available The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq to conduct the first expression analysis of human trigeminal ganglia (TG and dorsal root ganglia (DRG. We analyzed the data with a focus on G-protein coupled receptors (GPCRs and ion channels, which are (potentially involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues.

  19. Catecholamines reduce transient receptor potential vanilloid type 1 desensitization in cultured dorsal root ganglia neurons.

    Science.gov (United States)

    Filippi, A; Caruntu, C; Gheorghe, R O; Deftu, A; Amuzescu, B; Ristoiu, V

    2016-12-01

    Sympathetic nervous system and adrenergic receptors are involved in the modulation of dorsal root ganglia neuronal activity, with TRPV1 receptor as an important downstream effector. It is already known that adrenergic sensitization of TRPV1 receptors or catecholamine-induced TRPV1 upregulation are involved in increased excitability and pain via mainly α 1 adrenergic receptors, but it is not known if reduced TRPV1 desensitization is involved in this process, as well. Therefore, the aims of this study were to evaluate the effects of epinephrine and norepinephrine on TRPV1 desensitization induced by repeated applications of capsaicin and to assess what would be the involvement of the major α 1 , α 2 and β adrenergic receptor subtypes. Using calcium microfluorimetry, the effects were evaluated by exposure to 1 μM epinephrine or 10 μM norepinephrine, alone or in the presence of adrenergic receptor inhibitors (phentolamine, prazosin and propranolol) before a 4 th capsaicin application in a series of 5 consecutive capsaicin applications. The results showed that both catecholamines produced significant reduction of TRPV1 desensitization, which was mediated by α 1 , α 2 and β 2 receptors. This study completes the general information about TRPV1 sensitization via adrenergic stimulation and may open perspectives for novel pharmacological approaches in skin inflammatory disorders and pain therapy.

  20. Alterations in the vascular architecture of the dorsal root ganglia in a rat neuropathic pain model.

    Science.gov (United States)

    Kubícek, Lubos; Kopácik, Roman; Klusáková, Ilona; Dubový, Petr

    2010-04-20

    An alteration in the structural arrangement of blood vessels identified by RECA immunohistochemistry was studied in a rat L4 dorsal root ganglia (L4-DRG) neuropathic pain model. We compared a three-dimensional (3-D) reconstruction of the vascular architecture surrounding bodies of the primary sensory neurons in the L4-DRG of naïve rats with that of rats that had surgically undergone unilateral sciatic nerve ligature. Rhodamine-conjugated dextran (Fluoro-Ruby) was used for retrograde labelling of neurons, the axons of which had been injured by nerve ligature. In contrast to DRG from naïve rats and contralateral DRG from operated rats, an increased proportion of RECA+ vascular area and the appearance of nest-like arrangements of blood vessels around neuronal bodies with injured axons were observed in L4-DRG ipsilateral to the sciatic nerve ligature. Fractal analysis confirmed a higher degree of vascular branching, irregularity, and tortuosity in L4-DRG related with sciatic nerve injury. The results suggest that nerve injury induces changes in vascular architecture in associated DRG. Copyright 2010 Elsevier GmbH. All rights reserved.

  1. Na+ Channel Scn1b Gene Regulates Dorsal Root Ganglion Nociceptor Excitability in Vivo*

    Science.gov (United States)

    Lopez-Santiago, Luis F.; Brackenbury, William J.; Chen, Chunling; Isom, Lori L.

    2011-01-01

    Nociceptive dorsal root ganglion (DRG) neurons express tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) Na+ current (INa) mediated by voltage-gated Na+ channels (VGSCs). In nociceptive DRG neurons, VGSC β2 subunits, encoded by Scn2b, selectively regulate TTX-S α subunit mRNA and protein expression, ultimately resulting in changes in pain sensitivity. We hypothesized that VGSCs in nociceptive DRG neurons may also be regulated by β1 subunits, encoded by Scn1b. Scn1b null mice are models of Dravet Syndrome, a severe pediatric encephalopathy. Many physiological effects of Scn1b deletion on CNS neurons have been described. In contrast, little is known about the role of Scn1b in peripheral neurons in vivo. Here we demonstrate that Scn1b null DRG neurons exhibit a depolarizing shift in the voltage dependence of TTX-S INa inactivation, reduced persistent TTX-R INa, a prolonged rate of recovery of TTX-R INa from inactivation, and reduced cell surface expression of Nav1.9 compared with their WT littermates. Investigation of action potential firing shows that Scn1b null DRG neurons are hyperexcitable compared with WT. Consistent with this, transient outward K+ current (Ito) is significantly reduced in null DRG neurons. We conclude that Scn1b regulates the electrical excitability of nociceptive DRG neurons in vivo by modulating both INa and IK. PMID:21555511

  2. Membrane Mechanics of Primary Afferent Neurons in the Dorsal Root Ganglia of Rats.

    Science.gov (United States)

    Kanda, Hirosato; Gu, Jianguo G

    2017-04-25

    Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG). We further determined the roles of cytoskeleton and membrane lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane tension of ∼54 pN/μm, and the tension was significantly decreased to ∼29 pN/μm by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ∼79 pN/μm by methyl-β-cyclodextrin treatment to sequester membrane cholesterol. DRG neuron membrane stiffness was not significantly affected by the cytoskeleton disruption but was significantly increased after cholesterol sequestration. Our findings elucidate membrane mechanical properties of primary afferent neurons, which provide, to our knowledge, a new perspective on their sensory functions. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Comparison of AAV serotypes for gene delivery to dorsal root ganglion neurons.

    Science.gov (United States)

    Mason, Matthew R J; Ehlert, Erich M E; Eggers, Ruben; Pool, Chris W; Hermening, Stephan; Huseinovic, Angelina; Timmermans, Eric; Blits, Bas; Verhaagen, Joost

    2010-04-01

    For many experiments in the study of the peripheral nervous system, it would be useful to genetically manipulate primary sensory neurons. We have compared vectors based on adeno-associated virus (AAV) serotypes 1, 2, 3, 4, 5, 6, and 8, and lentivirus (LV), all expressing green fluorescent protein (GFP), for efficiency of transduction of sensory neurons, expression level, cellular tropism, and persistence of transgene expression following direct injection into the dorsal root ganglia (DRG), using histological quantification and qPCR. Two weeks after injection, AAV1, AAV5, and AAV6 had transduced the most neurons. The time course of GFP expression from these three vectors was studied from 1 to 12 weeks after injection. AAV5 was the most effective serotype overall, followed by AAV1. Both these serotypes showed increasing neuronal transduction rates at later time points, with some injections of AAV5 yielding over 90% of DRG neurons GFP(+) at 12 weeks. AAV6 performed well initially, but transduction rates declined dramatically between 4 and 12 weeks. AAV1 and AAV5 both transduced large-diameter neurons, IB4(+) neurons, and CGRP(+) neurons. In conclusion, AAV5 is a highly effective gene therapy vector for primary sensory neurons following direct injection into the DRG.

  4. Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

    Science.gov (United States)

    Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

    2011-10-01

    The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

  5. Plasticity of Select Primary Afferent Projections to the Dorsal Horn after a Lumbosacral Ventral Root Avulsion Injury and Root Replantation in Rats.

    Science.gov (United States)

    Bigbee, Allison J; Akhavan, Mahnaz; Havton, Leif A

    2017-01-01

    Injuries to the conus medullaris and cauda equina portions of the spinal cord result in neurological impairments, including paralysis, autonomic dysfunction, and pain. In experimental studies, earlier investigations have shown that a lumbosacral ventral root avulsion (VRA) injury results in allodynia, which may be ameliorated by surgical replantation of the avulsed ventral roots. Here, we investigated the long-term effects of an L6 + S1 VRA injury on the plasticity of three populations of afferent projections to the dorsal horn in rats. At 8 weeks after a unilateral L6 + S1 VRA injury, quantitative morphological studies of the adjacent L5 dorsal horn showed reduced immunoreactivity (IR) for the vesicular glutamate transporter, VGLUT1 and isolectin B4 (IB4) binding, whereas IR for calcitonin gene-related peptide (CGRP) was unchanged. The IR for VGLUT1 and CGRP as well as IB4 binding was at control levels in the L5 dorsal horn at 8 weeks following an acute surgical replantation of the avulsed L6 + S1 ventral roots. Quantitative morphological studies of the L5 dorsal root ganglia (DRGs) showed unchanged neuronal numbers for both the VRA and replanted series compared to shams. The portions of L5 DRG neurons expressing IR for VGLUT1 and CGRP, and IB4 binding were also the same between the VRA, replanted, and sham-operated groups. We conclude that the L5 dorsal horn shows selective plasticity for VGLUT1 and IB4 primary afferent projections after an L6 + S1 VRA injury and surgical repair.

  6. Plasticity of Select Primary Afferent Projections to the Dorsal Horn after a Lumbosacral Ventral Root Avulsion Injury and Root Replantation in Rats

    Directory of Open Access Journals (Sweden)

    Allison J. Bigbee

    2017-07-01

    Full Text Available Injuries to the conus medullaris and cauda equina portions of the spinal cord result in neurological impairments, including paralysis, autonomic dysfunction, and pain. In experimental studies, earlier investigations have shown that a lumbosacral ventral root avulsion (VRA injury results in allodynia, which may be ameliorated by surgical replantation of the avulsed ventral roots. Here, we investigated the long-term effects of an L6 + S1 VRA injury on the plasticity of three populations of afferent projections to the dorsal horn in rats. At 8 weeks after a unilateral L6 + S1 VRA injury, quantitative morphological studies of the adjacent L5 dorsal horn showed reduced immunoreactivity (IR for the vesicular glutamate transporter, VGLUT1 and isolectin B4 (IB4 binding, whereas IR for calcitonin gene-related peptide (CGRP was unchanged. The IR for VGLUT1 and CGRP as well as IB4 binding was at control levels in the L5 dorsal horn at 8 weeks following an acute surgical replantation of the avulsed L6 + S1 ventral roots. Quantitative morphological studies of the L5 dorsal root ganglia (DRGs showed unchanged neuronal numbers for both the VRA and replanted series compared to shams. The portions of L5 DRG neurons expressing IR for VGLUT1 and CGRP, and IB4 binding were also the same between the VRA, replanted, and sham-operated groups. We conclude that the L5 dorsal horn shows selective plasticity for VGLUT1 and IB4 primary afferent projections after an L6 + S1 VRA injury and surgical repair.

  7. Sigma-1 receptor expression in the dorsal root ganglion: Reexamination using a highly specific antibody.

    Science.gov (United States)

    Mavlyutov, Timur A; Duellman, Tyler; Kim, Hung Tae; Epstein, Miles L; Leese, Charlotte; Davletov, Bazbek A; Yang, Jay

    2016-09-07

    Sigma-1 receptor (S1R) is a unique pluripotent modulator of living systems and has been reported to be associated with a number of neurological diseases including pathological pain. Intrathecal administration of S1R antagonists attenuates the pain behavior of rodents in both inflammatory and neuropathic pain models. However, the S1R localization in the spinal cord shows a selective ventral horn motor neuron distribution, suggesting the high likelihood of S1R in the dorsal root ganglion (DRG) mediating the pain relief by intrathecally administered drugs. Since primary afferents are the major component in the pain pathway, we examined the mouse and rat DRGs for the presence of the S1R. At both mRNA and protein levels, quantitative RT-PCR (qRT-PCR) and Western confirmed that the DRG contains greater S1R expression in comparison to spinal cord, cortex, or lung but less than liver. Using a custom-made highly specific antibody, we demonstrated the presence of a strong S1R immuno-fluorescence in all rat and mouse DRG neurons co-localizing with the Neuron-Specific Enolase (NSE) marker, but not in neural processes or GFAP-positive glial satellite cells. In addition, S1R was absent in afferent terminals in the skin and in the dorsal horn of the spinal cord. Using immuno-electron microscopy, we showed that S1R is detected in the nuclear envelope and endoplasmic reticulum (ER) of DRG cells. In contrast to other cells, S1R is also located directly at the plasma membrane of the DRG neurons. The presence of S1R in the nuclear envelope of all DRG neurons suggests an exciting potential role of S1R as a regulator of neuronal nuclear activities and/or gene expression, which may provide insight toward new molecular targets for modulating nociception at the level of primary afferent neurons. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents

    OpenAIRE

    Trolle, Carl; Abrahamsson, Ninnie; König, Niclas; Vasylovska, Svitlana; Kozlova, Elena

    2014-01-01

    The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse bNCSCs implanted to the uninjured DRTZ after dorsal root ...

  9. Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury

    OpenAIRE

    Hoeber, Jan; Trolle, Carl; König, Niclas; Du, Zhongwei; Gallo, Alessandro; Hermans, Emmanuel; Aldskogius, Håkan; Shortland, Peter; Zhang, Su-Chun; Deumens, Ronald; Kozlova, Elena N

    2015-01-01

    Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural ...

  10. Functional Properties and Toxin Pharmacology of a Dorsal Root Ganglion Sodium Channel Viewed through its Voltage Sensors

    OpenAIRE

    Bosmans, Frank; Puopolo, Michelino; Martin-Eauclaire, Marie-France; Swartz, Kenton J.; Bean, Bruce Palmer

    2011-01-01

    The voltage-activated sodium (Nav) channel Nav1.9 is expressed in dorsal root ganglion (DRG) neurons where it is believed to play an important role in nociception. Progress in revealing the functional properties and pharmacological sensitivities of this non-canonical Nav channel has been slow because attempts to express this channel in a heterologous expression system have been unsuccessful. Here, we use a protein engineering approach to dissect the contributions of the four Nav1.9 voltage se...

  11. [Experimental research on substance P content of hypothalamus and dorsal root ganglia in rats with lumbar vertebrae Gucuofeng model].

    Science.gov (United States)

    Chen, Bo; Lin, Xun; Pang, Jian; Kong, Ling-jun; Zhan, Hong-sheng; Cheng, Ying-wu; Shi, Yin-yu

    2015-01-01

    To detect the effects of lumbar vertebrae Gucuofeng on the substance P content of hypothalamus and dorsal root ganglia in rat models. A hundred and twenty SPF level SD male rats with the weight of 350 to 450 g were randomly divided into rotary fixation group (RF group), simple fixation group (SF group) and sham-operation group (Sham group). The external link fixation system was implanted into the L4-L6 of rats in RF group and SF group; and in RF group, that the L5 spinous process was rotated to the right resulted in L4, L5, L6 spinous process not collinear; in SF group, the external link fixation system was simply implanted and not rotated. The rats of Sham group were not implanted the external link fixation system and only open and suture. The substance P content of hypothalamus and dorsal root ganglia were detected at 1, 4, 8, 12 weeks after operation. Substance P content of hypothalamus in RF group and SF group was lower than Sham group at 1, 4, 8 weeks after operation (Phypothalamus among three groups at 12 weeks after operation (P>0.05). Lumbar vertebrae Gucuofeng can inhibit the analgesic activity of substance P in hypothalamus and promote the synthesis and transmission of substance P in dorsal root ganglia, so as to cause or aggravate the pain.

  12. Anatomical study on the relationship between the dorsal root ganglion and the intervertebral disc in the lumbar spine

    Directory of Open Access Journals (Sweden)

    Emiliano Vialle

    2015-08-01

    Full Text Available ABSTRACTOBJECTIVE: To describe the location of the dorsal root ganglion in relation to the intervertebral disc, including the "triangular" safety zone for minimally invasive surgery in the lumbar spine. METHODS: Eight adult cadavers were dissected bilaterally in the lumbar region, using a posterolateral approach, so as to expose the L3L4 and L4L5 spaces, thereby obtaining measurements relating to the space between the intervertebral disc, pedicles cranial and caudal to the disc, path of the nerve root, dorsal ganglion and safety triangle. RESULTS: The measurements obtained were constant, without significant differences between levels or any laterality. The dorsal ganglion occupied the lateral border of the triangular safety zone in all the specimens analyzed. CONCLUSION: Precise localization of the ganglion shows that the safety margin for minimally invasive procedures is less than what is presented in studies that only involve measurements of the nerve root, thus perhaps explaining the presence of neuropathic pain after some of these procedures.

  13. [EFFECT OF PEPTIDE SEMAX ON SYNAPTIC ACTIVITY AND SHORT-TERM PLASTICITY OF GLUTAMATERGIC SYNAPSES OF CO-CULTURED DORSAL ROOT GANGLION AND DORSAL HORN NEURONS].

    Science.gov (United States)

    Shypshyna, M S; Veselovsky, N S; Myasoedov, N F; Shram, S I; Fedulova, S A

    2015-01-01

    The influence of long-term culturing (12 days in vitro) of dorsal root ganglion (DRG) and dorsal horn (DH) neurons with peptide Semax on the level of synaptic activity at co-cultures, as well as short-term plasticity in sensory synapses were studied. It has been shown that neuronal culturing with peptide at concentrations of 10 and 100 µM led to increasing the frequency of spontaneous glutamatergic postsynaptic currents in DH neurons to 71.7 ± 1.8% and 93.9 ± 3.1% (n = 6; P effect on the amplitude and frequency of miniature glutamatergic currents, but causes an increase of the amplitudes of spontaneous postsynaptic currents, as well as elevates the quantum content. The data show the increase of multivesicular glutamate release efficiency in neural networks of co-cultures following incubation with the peptide. Also Semax (10 and 100 µM) induces changes of the basic parameters of short-term plasticity in sensory synapses: (1) increasing the paired-pulse ratio from 0.53 ± 0.028 (n = 8) to 0.91 ± 0.072 (n = 6, P effect of Semax on the activity of glutamatergic synapses in neural networks of co-cultures, as well as the ability of the peptide to effectively modulate the short-term plasticity in sensory synapses.

  14. Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

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    Su Lin

    2011-11-01

    Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

  15. Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons

    Science.gov (United States)

    Stotz, Stephanie C.; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E.

    2008-01-01

    Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin. PMID:18461159

  16. Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP).

    Science.gov (United States)

    Eldabe, Sam; Burger, Katja; Moser, Heinrich; Klase, Daniel; Schu, Stefan; Wahlstedt, Anders; Vanderick, Bernard; Francois, Eric; Kramer, Jeffery; Subbaroyan, Jeyakumar

    2015-10-01

    Phantom limb pain (PLP) is a neuropathic condition in which pain is perceived as arising from an amputated limb. PLP is distinct from, although associated with, pain in the residual limb and nonpainful phantom sensations of the missing limb. Its treatment is extremely challenging; pharmaceutical options, while commonly employed, may be insufficient or intolerable. Neuromodulatory interventions such as spinal cord stimulation have generated mixed results and may be limited by poor somatotopic specificity. It was theorized that dorsal root ganglion (DRG) neuromodulation may be more effective. Patients trialed a DRG neurostimulation system for their PLP and were subsequently implanted if results were positive. Retrospective chart review was completed, including pain ratings on a 100-mm visual analogue scale (VAS) and patient-reported outcomes. Across eight patients, the average baseline pain rating was 85.5 mm. At follow-up (mean of 14.4 months), pain was rated at 43.5 mm. Subjective ratings of quality of life and functional capacity improved. Some patients reduced or eliminated pain medications. Patients reported precise concordance of the paresthesia with painful regions, including in their phantom limbs; in one case, stimulation eliminated PLP as well as nonpainful phantom sensations. Three patients experienced a diminution of pain relief, despite good initial outcomes. DRG neuromodulation may be an effective tool in treating this pain etiology. Clinical outcomes in this report support recent converging evidence suggesting that the DRG may be the site of PLP generation and/or maintenance. Further research is warranted to elucidate mechanisms and optimal treatment pathways. © 2015 International Neuromodulation Society.

  17. Trinitrobenzenesulphonic acid colitis alters Na 1.8 channel expression in mouse dorsal root ganglia neurons.

    Science.gov (United States)

    King, D E; Macleod, R J; Vanner, S J

    2009-08-01

    Visceral inflammation evokes hyperexcitability in nociceptive dorsal root ganglia (DRG) neurons and these changes are associated with increased voltage-gated sodium channel (Na(v)) 1.8 current density, but the molecular determinants of these changes are unclear. This study used Western blotting to measure changes in Na(v) 1.7, 1.8 and 1.9 protein expression during trinitrobenzenesulphonic acid (TNBS) colitis and quantitative polymerase chain reaction (PCR) to examine corresponding changes in mRNA. Colonic neurons were labelled with the retrograde tracer Fast Blue injected into the wall of the distal colon and quantitative PCR performed on laser-captured labelled colonic neurons from ganglia at T9-13 or unlabelled DRG neurons from the upper spinal cord. Immunohistochemistry and western blots were performed on whole DRG from the same sites. Fast Blue-labelled neurons demonstrated Na(v) 1.7, 1.8 and 1.9 immunoreactivity. On day 7 of colitis, which correlated with electrophysiological studies, there was a threefold increase in Na(v) 1.8 protein in ganglia from T9 to 13, but Na(v) 1.7 and 1.9 levels were unchanged. There was no corresponding change in the Na(v) 1.8 alpha-subunit mRNA levels. However, on days 2 and 4, Na(v) 1.8 mRNA was decreased 10-fold. Na(v) 1.8 protein and mRNA levels were unchanged in neurons isolated from ganglia in the upper spinal cord, where colonic neurons are not found. These findings suggest that the TNBS evoked increase in Na(v) 1.8 currents is associated with increased numbers of channels. The absence of corresponding changes in transcript suggests a translational or post-translational mechanism, but the 10-fold recovery of transcript preceding this time point also demonstrates a complex transcriptional regulation.

  18. Sources of axonal calcium loading during in vitro ischemia of rat dorsal roots.

    Science.gov (United States)

    Petrescu, Nicolae; Micu, Ileana; Malek, Sameh; Ouardouz, Mohamed; Stys, Peter K

    2007-04-01

    A detailed understanding of injury mechanisms in peripheral nerve fibers will help guide successful design of therapies for peripheral neuropathies. This study was therefore undertaken to examine the ionic mechanisms of Ca2+ overload in peripheral myelinated fibers subjected to chemical inhibition of energy metabolism. Myelinated axons from rat dorsal roots were co-loaded with Ca2+-sensitive (Oregon Green BAPTA-1) and Ca2+-insensitive (Alexa Fluor 594) dextran-conjugated fluorophores and imaged using confocal laser scanning microscopy. Axoplasmic regions were clearly outlined by the Ca2+-insensitive dye, from which axonal Ca2+-dependent fluorescence changes (FCa.ax) were measured. Block of Na+-K+ ATPase (ouabain), opening of Na+ channels (veratridine), and inhibiting energy metabolism (iodoacetate + NaN3) caused a rapid rise in FCa.ax to 96% above control after 30 min. Chemical ischemia (iodoacetate + NaN3) caused a more gradual increase in FCa.ax (54%), which was almost completely dependent on bath Ca2+, indicating that most of the Ca2+ accumulation occurred via influx across the axolemma. Na+ channel block (tetrodotoxin) reduced ischemic FCa.ax rise (14%); however, inhibition of L-type Ca2+ channels (nimodipine) had no effect (60%). In contrast, Na+-Ca2+ exchange inhibition (KB-R7943) significantly reduced ischemic FCa.ax rise (18%). Together our results indicate that the bulk of Ca2+ overload in injured peripheral myelinated axons occurs via reverse Na+-Ca2+ exchange, driven by axonal Na+ accumulation through voltage-gated tetrodotoxin-sensitive Na+ channels. This mechanism may represent a viable therapeutic target for peripheral neuropathies.

  19. Activation of neurokinin-1 receptors increases the excitability of guinea pig dorsal root ganglion cells.

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    Zhang, Xiulin; Pietra, Claudio; Lovati, Emanuela; de Groat, William C

    2012-10-01

    The suppression of overactive bladder symptoms in patients and overactive bladder reflexes in animal models by neurokinin (NK)-1 receptor antagonists raises the possibility that these drugs target sensory neurons. This mechanism was evaluated by examining the interactions between a specific NK-1 agonist, [Sar(9),Met(O(2))(11)]-substance P (Sar-Met-SP), and a potent NK-1 antagonist, netupitant (NTP), on small size (20-30 μm) dissociated L6 and S1 dorsal root ganglion (DRG) neurons from female guinea pigs. Current-clamp recording revealed that Sar-Met-SP (1 μM) elicited membrane depolarization (average 8.05 ± 1.38 mV) in 27% (18 of 65) of DRG neurons. In 74% of the remaining neurons (35 of 47) Sar-Met-SP decreased the rheobase for action potential (AP) generation and increased the response to a suprathreshold stimulus (3 times rheobase) without changing the membrane potential. Sar-Met-SP also induced changes in the action potential (AP) wave form, including 1) an increase in overshoot (average 5 mV, n = 35 neurons), 2) a prolongation of AP duration (from 4.64 to 5.29 ms, n = 34), and 3) a reduction in the maximal rate of AP repolarization. NTP (200 nM) reversed the Sar-Met-SP-induced changes. Ca(2+) imaging showed that application of Sar-Met-SP (1 μM) decreased the tachyphylaxis induced by repeated application of capsaicin (0.5 μM), an effect blocked by pretreatment with NTP (200 nM). These results raise the possibility that activation of NK-1 receptors in primary sensory neurons plays a role in the generation of overactive bladder and that block of NK-1 receptors in these neurons may contribute to efficacy of NK-1 antagonists in the treatment of overactive bladder symptoms.

  20. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

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    Stephanie C Stotz

    2008-05-01

    Full Text Available Transient receptor potential (TRP ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1, and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate, consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  1. The dorsal root ganglion in chronic pain and as a target for neuromodulation: a review.

    Science.gov (United States)

    Krames, Elliot S

    2015-01-01

    In the not-too-distant past, the dorsal root ganglion (DRG) was portrayed as a passive neural structure without involvement in the development or maintenance of chronic neuropathic pain (NP). The DRG was thought of as a structure that merely "supported" physiologic communication between the peripheral nervous system (PNS) and the central nervous system (CNS). Newer scientific information regarding the anatomic and physiologic changes that occur within the DRG as a result of environmental pressures has dispelled this concept and suggests that the DRG is an active participant in the development of NP. This new information, along with new clinical data showing that stimulation of the DRG reduces intensity of pain, suggests that the DRG can be a robust target for neuromodulation therapies. A review of the anatomical and physiological literature regarding the role of the DRG in the development of NP was performed utilizing SciBase, PubMed, and Google Scholar. The information gathered was used to lay an anatomic and physiologic foundation for establishing the DRG as a relevant target for neuromodulation therapies and to formulate a hypothesis as to how electrical stimulation of the DRG might reverse the process and perception of NP. The DRG is an active participant in the development of NP. DRG stimulation has multiple effects on the abnormal changes that occur within the DRG as a result of peripheral afferent fiber injury. The sum total of these stimulation effects is to stabilize and decrease hyperexcitability of DRG neurons and thereby decrease NP. © 2014 International Neuromodulation Society.

  2. Isolated dorsal root ganglion neurones inhibit receptor-dependent adenylyl cyclase activity in associated glial cells

    Science.gov (United States)

    Ng, KY; Yeung, BHS; Wong, YH; Wise, H

    2013-01-01

    Background and Purpose Hyper-nociceptive PGE2 EP4 receptors and prostacyclin (IP) receptors are present in adult rat dorsal root ganglion (DRG) neurones and glial cells in culture. The present study has investigated the cell-specific expression of two other Gs-protein coupled hyper-nociceptive receptor systems: β-adrenoceptors and calcitonin gene-related peptide (CGRP) receptors in isolated DRG cells and has examined the influence of neurone–glial cell interactions in regulating adenylyl cyclase (AC) activity. Experimental Approach Agonist-stimulated AC activity was determined in mixed DRG cell cultures from adult rats and compared with activity in DRG neurone-enriched cell cultures and pure DRG glial cell cultures. Key Results Pharmacological analysis showed the presence of Gs-coupled β2-adrenoceptors and CGRP receptors, but not β1-adrenoceptors, in all three DRG cell preparations. Agonist-stimulated AC activity was weakest in DRG neurone-enriched cell cultures. DRG neurones inhibited IP receptor-stimulated glial cell AC activity by a process dependent on both cell–cell contact and neurone-derived soluble factors, but this is unlikely to involve purine or glutamine receptor activation. Conclusions and Implications Gs-coupled hyper-nociceptive receptors are readily expressed on DRG glial cells in isolated cell cultures and the activity of CGRP, EP4 and IP receptors, but not β2-adrenoceptors, in glial cells is inhibited by DRG neurones. Studies using isolated DRG cells should be aware that hyper-nociceptive ligands may stimulate receptors on glial cells in addition to neurones, and that variable numbers of neurones and glial cells will influence absolute measures of AC activity and affect downstream functional responses. PMID:22924655

  3. Enrichment and proteomic analysis of plasma membrane from rat dorsal root ganglions

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    Lin Yong

    2009-11-01

    Full Text Available Abstract Background Dorsal root ganglion (DRG neurons are primary sensory neurons that conduct neuronal impulses related to pain, touch and temperature senses. Plasma membrane (PM of DRG cells plays important roles in their functions. PM proteins are main performers of the functions. However, mainly due to the very low amount of DRG that leads to the difficulties in PM sample collection, few proteomic analyses on the PM have been reported and it is a subject that demands further investigation. Results By using aqueous polymer two-phase partition in combination with high salt and high pH washing, PMs were efficiently enriched, demonstrated by western blot analysis. A total of 954 non-redundant proteins were identified from the plasma membrane-enriched preparation with CapLC-MS/MS analysis subsequent to protein separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE or shotgun digestion. 205 (21.5% of the identified proteins were unambiguously assigned as PM proteins, including a large number of signal proteins, receptors, ion channel and transporters. Conclusion The aqueous polymer two-phase partition is a simple, rapid and relatively inexpensive method. It is well suitable for the purification of PMs from small amount of tissues. Therefore, it is reasonable for the DRG PM to be enriched by using aqueous two-phase partition as a preferred method. Proteomic analysis showed that DRG PM was rich in proteins involved in the fundamental biological processes including material exchange, energy transformation and information transmission, etc. These data would help to our further understanding of the fundamental DRG functions.

  4. Lentiviral gene transfer into the dorsal root ganglion of adult rats

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    Park Frank

    2011-08-01

    Full Text Available Abstract Background Lentivector-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 requirements for efficient transduction into neuronal cells in vitro and adult rat DRG in vivo. Results In vitro, lentivectors expressing enhanced green fluorescent protein (EGFP under control of the human elongation factor 1α (EF1α promoter and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV-G envelope exhibited the best performance in the transfer of EGFP into an immortalized DRG sensory neuron cell line at low multiplicities of infection (MOIs, and into primary cultured DRG neurons at higher MOIs. In vivo, injection of either first or second-generation EF1α-EGFP lentivectors directly into adult rat DRGs led to transduction rates of 19 ± 9% and 20 ± 8% EGFP-positive DRG neurons, respectively, detected at 4 weeks post injection. Transduced cells included a full range of neuronal phenotypes, including myelinated neurons as well as both non-peptidergic and peptidergic nociceptive unmyelinated neurons. Conclusion VSV-G pseudotyped lentivectors containing the human elongation factor 1α (EF1α-EGFP expression cassette demonstrated relatively efficient transduction to sensory neurons following direct injection into the DRG. These results clearly show the potential of lentivectors as a viable system for delivering target genes into DRGs to explore basic mechanisms of neuropathic pain, with the potential for future clinical use in treating chronic pain.

  5. Cannabinoids inhibit acid-sensing ion channel currents in rat dorsal root ganglion neurons.

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    Yu-Qiang Liu

    Full Text Available Local acidosis has been found in various pain-generating conditions such as inflammation and tissue injury. Cannabinoids exert a powerful inhibitory control over pain initiation via peripheral cognate receptors. However, the peripheral molecular targets responsible for the antinociceptive effects of cannabinoids are still poorly understood. Here, we have found that WIN55,212-2, a cannabinoid receptor agonist, inhibits the activity of native acid-sensing ion channels (ASICs in rat dorsal root ganglion (DRG neurons. WIN55,212-2 dose-dependently inhibited proton-gated currents mediated by ASICs. WIN55,212-2 shifted the proton concentration-response curve downwards, with an decrease of 48.6±3.7% in the maximum current response but with no significant change in the EC(50 value. The inhibition of proton-gated current induced by WIN55,212-2 was almost completely blocked by the selective CB1 receptor antagonist AM 281, but not by the CB2 receptor antagonist AM630. Pretreatment of forskolin, an AC activator, and the addition of cAMP also reversed the inhibition of WIN55,212-2. Moreover, WIN55,212-2 altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. Finally, WIN55,212-2 attenuated nociceptive responses to injection of acetic acid in rats. These results suggest that WIN55,212-2 inhibits the activity of ASICs via CB1 receptor and cAMP dependent pathway in rat primary sensory neurons. Thus, cannabinoids can exert their analgesic action by interaction with ASICs in the primary afferent neurons, which was novel analgesic mechanism of cannabinoids.

  6. Impaired axonal regeneration by isolectin B4-binding dorsal root ganglion neurons in vitro.

    Science.gov (United States)

    Leclere, Pascal G; Norman, Emma; Groutsi, Filitsa; Coffin, Robert; Mayer, Ulrike; Pizzey, John; Tonge, David

    2007-01-31

    The subpopulation of dorsal root ganglion (DRG) neurons recognized by Griffonia simplicifolia isolectin B4 (IB4) differ from other neurons by expressing receptors for glial cell line-derived neurotrophic factor (GDNF) rather than neurotrophins. Additionally, IB4-labeled neurons do not express the laminin receptor, alpha7-integrin (Gardiner et al., 2005), necessary for optimal axonal regeneration in the peripheral nervous system. In cultures of dissociated DRG neurons of adult mice on laminin, robust spontaneous neurite outgrowth from IB4-negative neurons occurs and is strongly enhanced by previous axotomy. In contrast, IB4-labeled neurons show little neurite outgrowth and do not express GAP 43, even after axotomy or culture with GDNF. Moreover, growth of their axons through collagen gels is impaired compared with other DRG neurons. To determine whether the sparse neurite outgrowth of IB4-labeled neurons is attributable to lack of integrin expression, DRG cultures were infected with a herpes simplex 1 vector encoding alpha7-integrin, but its forced expression failed to promote neurite outgrowth in either IB4-labeled or other DRG neurons or in cultured adult retinal ganglion cells. Forced coexpression of both alpha7-integrin and GAP 43 also failed to promote neurite outgrowth in IB4-labeled neurons. In addition, cultured sciatic nerve segments were found to release much lower levels of GDNF, demonstrated by ELISA, than nerve growth factor. These findings together with their impaired intrinsic axonal regeneration capacity may contribute to the known vulnerability of the IB4-labeled population of DRG neurons to peripheral nerve injury.

  7. Single-cell analysis of sodium channel expression in dorsal root ganglion neurons.

    Science.gov (United States)

    Ho, Cojen; O'Leary, Michael E

    2011-01-01

    Sensory neurons of the dorsal root ganglia (DRG) express multiple voltage-gated sodium (Na) channels that substantially differ in gating kinetics and pharmacology. Small-diameter (30 μm) predominately express fast TTX-S Na current. Na channel expression was further investigated using single-cell RT-PCR to measure the transcripts present in individually harvested DRG neurons. Consistent with cellular electrophysiology, the small neurons expressed transcripts encoding for both TTX-S (Nav1.1, Nav1.2, Nav1.6, and Nav1.7) and TTX-R (Nav1.8 and Nav1.9) Na channels. Nav1.7, Nav1.8 and Nav1.9 were the predominant Na channels expressed in the small neurons. The large neurons highly expressed TTX-S isoforms (Nav1.1, Nav1.6, and Nav1.7) while TTX-R channels were present at comparatively low levels. A unique subpopulation of the large neurons was identified that expressed TTX-R Na current and high levels of Nav1.8 transcript. DRG neurons also displayed substantial differences in the expression of neurofilaments (NF200, peripherin) and Necl-1, a neuronal adhesion molecule involved in myelination. The preferential expression of NF200 and Necl-1 suggests that large-diameter neurons give rise to thick myelinated axons. Small-diameter neurons expressed peripherin, but reduced levels of NF200 and Necl-1, a pattern more consistent with thin unmyelinated axons. Single-cell analysis of Na channel transcripts indicates that TTX-S and TTX-R Na channels are differentially expressed in large myelinated (Nav1.1, Nav1.6, and Nav1.7) and small unmyelinated (Nav1.7, Nav1.8, and Nav1.9) sensory neurons. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Propofol up-regulates Mas receptor expression in dorsal root ganglion neurons.

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    Cao, Lijun; Xun, Junmei; Jiang, Xinghua; Tan, Rong

    2013-08-01

    Mas is a functional binding site for angiotensin (Ang)-(1-7), a critical component of the renin-angiotensin system that is involved in processing nociceptive information. A recent study reported the localization of Mas in rat dorsal root ganglia (DRG) and demonstrated that Ang-(1-7) produced a dose-dependent peripheral antinociceptive effect in rats through the Mas receptor by an opioid-independent mechanism. In the present study, we for the first time examined the effect of propofol on Mas expression in cultured DRG neurons. We treated rat DRG neurons with propofol at different concentrations (0.1, 0.5, 1, 5 or 10 microM) for different length of time (0.5, 1, 2, 4 or 6 h) with or without transcription inhibitor actinomycin D or different kinase inhibitors. Propofol increased the Mas receptormRNA level in a statistically significant dose- and time-dependent manner within 4 h, which led to dose-dependent up-regulation of the Mas receptor protein level as well as Ang-(1-7) binding on the cell membrane. Actinomycin D (1 mg/ml) and p38 mitogen-activated protein kinase inhibitor PD169316 (25 microM) completely abolished the effect of propofol on Mas receptor expression in DRG neurons. In conclusion, we demonstrate that propofol markedly up-regulates Mas receptor expression at the transcription level in DRG neurons by a p38 MAPK-dependent mechanism. This study provides new insights into the mechanisms of action of propofol in peripheral antinociception, and suggests a new regulatory mechanism on the Ang-(1-7)/Mas axis in the peripheral nervous system.

  9. Chronic nerve injury-induced Mas receptor expression in dorsal root ganglion neurons alleviates neuropathic pain.

    Science.gov (United States)

    Zhao, Yuanting; Qin, Yue; Liu, Tuanjiang; Hao, Dingjun

    2015-12-01

    Neuropathic pain, which is characterized by hyperalgesia, allodynia and spontaneous pain, is one of the most painful symptoms that can be experienced in the clinic. It often occurs as a result of injury to the peripheral nerves, dorsal root ganglion (DRG), spinal cord or brain. The renin-angiotensin system (RAS) plays an important role in nociception. As an essential component of the RAS, the angiotensin (Ang)-(1-7)/Mas axis may be involved in antinociception. The aim of the present study was to explore the expression pattern of Mas in DRG neurons following chronic nerve injury and examine the effects of Mas inhibition and activation on neuropathic pain in a chronic constriction injury (CCI) rat model. The results showed, that compared with the sham group, CCI caused a time-dependent induction of Mas expression at both the mRNA and the protein levels in DRG neurons. Consistent with the results, isolated DRG neurons showed a time-dependent increase in Ang-(1-7) binding on the cell membrane following the CCI surgery, but not the sham surgery. Compared with the sham control groups, CCI significantly decreased the paw withdrawal latency and threshold, and this was markedly improved and aggravated by intrathecal injection of the selective Mas agonist Ang-(1-7) and the selective Mas inhibitor D-Pro7-Ang-(1-7), respectively. In conclusion, this study has provided the first evidence, to the best of our knowledge, that the Mas expression in DRG neurons is time-dependently induced by chronic nerve injury and that the intrathecal activation and inhibition of Mas can improve and aggravate CCI-induced neuropathic pain, respectively. This study has provided novel insights into the pathophysiological process of neuropathic pain and suggests that the Ang-(1-7)/Mas axis could be an effective therapeutic target for neuropathic pain, warranting further study.

  10. Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

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    Leonidas Apostolidis

    Full Text Available To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP by magnetic resonance neurography (MRN.Twenty patients (7 female, 13 male, 58.9±10.0 years with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG, sciatic nerve normalized T2 (nT2 signal and caliber, and fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD. Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001 was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80 and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16. AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

  11. Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

    Science.gov (United States)

    Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

    2014-06-01

    Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

  12. Photobiomodulation of the dorsal root ganglion for the treatment of low back pain: A pilot study.

    Science.gov (United States)

    Holanda, Vanessa Milanesi; Chavantes, Maria Cristina; Silva, Daniela Fatima Teixeira; de Holanda, Carlos Vanderlei M; de Oliveira, José Oswaldo; Wu, Xingjia; Anders, Juanita J

    2016-09-01

    Chronic low back pain is a worldwide public health issue with high socioeconomic impact. The aim of this study was to determine the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for chronic axial low back pain compared to lidocaine injection and radiofrequency treatment. Twenty-eight patients were randomly divided into three treatment groups: lidocaine injection, radiofrequency, or laser. The second intervertebral foramen between the second and third lumbar vertebrae was accessed by percutaneous needle puncture bilaterally, guided by fluoroscopy. In the local anesthetic group, injection of 1 ml lidocaine without epinephrine was applied through a 20-gauge (G20) Quincke tip spinal needle inserted in the second lumbar intervertebral foramen. In the radiofrequency group, the probe (150 mm long with a 5 mm active tip) was directed through a G20 needle placed in the second lumbar intervertebral foramen and neuromodulation was done with a radiofrequency of Cosman G4® in pulses of 20 ms with wash-out period of 480 ms, for 300 seconds at 42°C. A single treatment was used. In the laser treatment group, a continuous wave, 808 nm wavelength diode laser (Photon Lase III® DCM, Brazil), with an output power of 100 mW was used for a single treatment. An 18 gauge needle was placed in the second lumbar intervertebral foramen guided by fluoroscopy. Light was delivered through a 600 µm optical fiber placed in the G18 needle. The tip of the fiber extended 5 mm beyond the tip of the needle in the second lumbar intervertebral foramen. The beam spot size was 0.003 cm(2) , irradiance = 35W/cm(2) , exposure time = 84 seconds, energy density = 2800J/cm(2) , total energy was 8.4 J. The low back pain score was assessed by the visual analog scale (VAS) and Pain Relief Scale (PRS) pre, post procedure and in 1 month follow up. Temperature was measured using a digital thermometer. All patients in the local

  13. Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia.

    Science.gov (United States)

    Raymond, Christopher K; Castle, John; Garrett-Engele, Philip; Armour, Christopher D; Kan, Zhengyan; Tsinoremas, Nicholas; Johnson, Jason M

    2004-10-29

    Molecular medicine requires the precise definition of drug targets, and tools are now in place to provide genome-wide information on the expression and alternative splicing patterns of any known gene. DNA microarrays were used to monitor transcript levels of the nine well-characterized alpha-subunit sodium channel genes across a broad range of tissues from cynomolgus monkey, a non-human primate model. Alternative splicing of human transcripts for a subset of the genes that are expressed in dorsal root ganglia, SCN8A (Na(v)1.6), SCN9A (Na(v)1.7), and SCN11A (Na(v)1.9) was characterized in detail. Genomic sequence analysis among gene family paralogs and between cross-species orthologs suggested specific alternative splicing events within transcripts of these genes, all of which were experimentally confirmed in human tissues. Quantitative PCR revealed that certain alternative splice events are uniquely expressed in dorsal root ganglia. In addition to characterization of human transcripts, alternatively spliced sodium channel transcripts were monitored in a rat model for neuropathic pain. Consistent down-regulation of all transcripts was observed, as well as significant changes in the splicing patterns of SCN8A and SCN9A.

  14. S3 Dorsal Root Ganglion/Nerve Root Stimulation for Refractory Postsurgical Perineal Pain: Technical Aspects of Anchorless Sacral Transforaminal Lead Placement

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    X. Zuidema

    2016-01-01

    Full Text Available Chronic perineal pain limits patients in physical and sexual activities, leading to social and psychological distress. In most cases, this pain develops after surgery in the urogenital area or as a consequence of trauma. Neuromodulation is one of the options in chronic postsurgical perineal pain treatment. We present a case of refractory perineal pain after right sided surgical resection of a Bartholin’s cyst which was treated with third sacral nerve root/dorsal root ganglion stimulation using the transforaminal approach. We describe a new anchorless lead placement technique using a unique curved lead delivery sheath. We postulate that this new posterior foraminal technique of lead placement is simple, safe, and reversible and may lower the occurrence of lead related complications.

  15. Inhibition of tetrodotoxin-resistant sodium current in dorsal root ganglia neurons mediated by D1/D5 dopamine receptors.

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    Galbavy, William; Safaie, Elham; Rebecchi, Mario J; Puopolo, Michelino

    2013-11-28

    Dopaminergic fibers originating from area A11 of the hypothalamus project to different levels of the spinal cord and represent the major source of dopamine. In addition, tyrosine hydroxylase, the rate-limiting enzyme for the synthesis of catecholamines, is expressed in 8-10% of dorsal root ganglia (DRG) neurons, suggesting that dopamine may be released in the dorsal root ganglia. Dopamine has been shown to modulate calcium current in DRG neurons, but the effects of dopamine on sodium current and on the firing properties of small DRG neurons are poorly understood. The effects of dopamine and dopamine receptor agonists were tested on the tetrodotoxin-resistant (TTX-R) sodium current recorded from acutely dissociated small (diameter ≤ 25 μm) DRG neurons. Dopamine (20 μM) and SKF 81297 (10 μM) caused inhibition of TTX-R sodium current in small DRG neurons by 23% and 37%, respectively. In contrast, quinpirole (20 μM) had no effects on the TTX-R sodium current. Inhibition by SKF 81297 of the TTX-R sodium current was not affected when the protein kinase A (PKA) activity was blocked with the PKA inhibitory peptide (6-22), but was greatly reduced when the protein kinase C (PKC) activity was blocked with the PKC inhibitory peptide (19-36), suggesting that activation of D1/D5 dopamine receptors is linked to PKC activity. Expression of D1and D5 dopamine receptors in small DRG neurons, but not D2 dopamine receptors, was confirmed by Western blotting and immunofluorescence analysis. In current clamp experiments, the number of action potentials elicited in small DRG neurons by current injection was reduced by ~ 30% by SKF 81297. We conclude that activation of D1/D5 dopamine receptors inhibits TTX-R sodium current in unmyelinated nociceptive neurons and dampens their intrinsic excitability by reducing the number of action potentials in response to stimulus. Increasing or decreasing levels of dopamine in the dorsal root ganglia may serve to adjust the sensitivity of

  16. CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine

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    Brown, Jacob D.; Saeed, Maythem; Do, Loi; Braz, Joao; Basbaum, Allan I.; Iadarola, Michael J.; Wilson, David M.; Dillon, William P.

    2016-01-01

    One approach to analgesia is to block pain at the site of origin or along the peripheral pathway by selectively ablating pain-transmitting neurons or nerve terminals directly. The heat/capsaicin receptor (TRPV1) expressed by nociceptive neurons is a compelling target for selective interventional analgesia because it leaves somatosensory and proprioceptive neurons intact. Resiniferatoxin (RTX), like capsaicin, is a TRPV1 agonist but has greater potency. We combine RTX-mediated inactivation with the precision of computed tomography (CT)–guided delivery to ablate peripheral pain fibers in swine. Under CT guidance, RTX was delivered unilaterally around the lumbar dorsal root ganglia (DRG), and vehicle only was administered to the contralateral side. During a 4-week observation period, animals demonstrated delayed or absent withdrawal responses to infrared laser heat stimuli delivered to sensory dermatomes corresponding to DRG receiving RTX treatment. Motor function was unimpaired as assessed by disability scoring and gait analysis. In treated DRG, TRPV1 mRNA expression was reduced, as were nociceptive neuronal perikarya in ganglia and their nerve terminals in the ipsilateral dorsal horn. CT guidance to precisely deliver RTX to sites of peripheral pain transmission in swine may be an approach that could be tailored to block an array of clinical pain conditions in patients. PMID:26378245

  17. Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

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    Javier Sábado

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs. Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations of superoxide dismutase 1 (SOD1 gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used the SOD1G93A mouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

  18. Growth of rat dorsal root ganglion neurons on a novel self-assembling scaffold containing IKVAV sequence

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    Zou Zhenwei; Zheng Qixin [Department of Orthopaedics, Union Hospital, Tongji Medical college of Huazhong University of science and technology, Wuhan, 430022 (China); Wu Yongchao, E-mail: wuyongchao@hotmail.com [Department of Orthopaedics, Union Hospital, Tongji Medical college of Huazhong University of science and technology, Wuhan, 430022 (China); Song Yulin; Wu Bin [Department of Orthopaedics, Union Hospital, Tongji Medical college of Huazhong University of science and technology, Wuhan, 430022 (China)

    2009-08-31

    The potential benefits of self-assembly in synthesizing materials for the treatment of both peripheral and central nervous system disorders are tremendous. In this study, we synthesized peptide-amphiphile (PA) molecules containing IKVAV sequence and induced self-assembly of the PA solutions in vitro to form nanofiber gels. Then, we tested the characterization of gels by transmission electron microscopy and demonstrated the biocompatibility of this gel towards rat dorsal root ganglion neurons. The nanofiber gel was formed by self-assembly of IKVAV PA molecules, which was triggered by metal ions. The fibers were 7-8 nm in diameter and with lengths of hundreds of nanometers. Gels were shown to be non-toxic to neurons and able to promote neurons adhesion and neurite sprouting. The results indicated that the self-assembling scaffold containing IKVAV sequence had excellent biocompatibility with adult sensory neurons and could be useful in nerve tissue engineering.

  19. Dorsal Root Ganglion Stimulation as a Salvage Treatment for Complex Regional Pain Syndrome Refractory to Dorsal Column Spinal Cord Stimulation: A Case Series.

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    Yang, Ajax; Hunter, Corey W

    2017-10-01

    The efficacy of traditional spinal cord stimulation (t-SCS) tends to decay over time in patients with complex regional pain syndrome (CRPS). While it has been shown that dorsal root ganglion (DRG) stimulation is extremely effective in t-SCS-naïve patients with CRPS, its efficacy in patients who had previously failed t-SCS is unknown. Given that DRG-SCS and t-SCS target different spinal pathways, a failure with t-SCS should not automatically preclude a patient from attempting DRG-SCS. Two patients with lower extremity CRPS, previously implanted with t-SCS systems, experienced relapses in the pain despite exhaustive reprogramming. Both patients were offered DRG stimulation as a means to salvage treatment. Patient 1 reported 90% pain reduction with significant gait improvement during the DRG stimulation trial. The patient subsequently proceeded to implant and have the t-SCS implantable pulse generator explanted. Patient 2 was unable to undergo a trial with DRG-SCS because of health insurance constraints, so she elected to undergo a surgical revision of her existing system whereby a DRG-SCS system was added to the existing t-SCS to create a hybrid system with two implantable pulse generators. The patient reported an immediate improvement in pain because of the introduction of the DRG-SCS. Additionally, she was instructed to document her pain scores with each system on individually, as well as with both on-her pain scores were at the lowest with the DRG-SCS on by itself. At eight-month follow-up, both patients reported sustained pain improvement and retained their functional gains. Our case series demonstrates that a failure of t-SCS is not necessarily a failure of neurostimulation as a whole. The efficacy of DRG-SCS is independent of prior t-SCS therapy outcomes in these two patients and a history of t-SCS failure serves no predictive value in these two patients for future DRG stimulation success. Therefore, DRG-SCS can be considered as a reasonable next-step to

  20. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

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    Chiaki Murayama

    2015-08-01

    Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

  1. The effects of ropivacaine hydrochloride on the expression of CaMK II mRNA in the dorsal root ganglion neurons.

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    Wen, Xianjie; Lai, Xiaohong; Li, Xiaohong; Zhang, Tao; Liang, Hua

    2016-12-01

    In this study, we identified the subtype of Calcium/calmodulin-dependent protein kinase II (CaMK II) mRNA in dorsal root ganglion neurons and observed the effects of ropivacaine hydrochloride in different concentration and different exposure time on the mRNA expression. Dorsal root ganglion neurons were isolated from the SD rats and cultured in vitro. The mRNA of the CaMK II subtype in dorsal root ganglion neurons were detected by real-time PCR. As well as, the dorsal root ganglion neurons were treated with ropivacaine hydrochloride in different concentration (1mM,2mM, 3mM and 4mM) for the same exposure time of 4h, or different exposure time (0h,2h,3h,4h and 6h) at the same concentration(3mM). The changes of the mRNA expression of the CaMK II subtype were observed with real-time PCR. All subtype mRNA of the CaMK II, CaMK IIα, CaMK IIβ, CaMK II δ, CaMK IIγ, can be detected in dorsal root ganglion neurons. With the increased of the concentration and exposure time of the ropivacaine hydrochloride, all the subtype mRNA expression increased. Ropivacaine hydrochloride up-regulate the CaMK IIβ, CaMK IIδ, CaMK IIg mRNA expression with the concentration and exposure time increasing. The nerve blocking or the neurotoxicity of the ropivacaine hydrochloride maybe involved with CaMK II. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. eIF4E Phosphorylation Influences Bdnf mRNA Translation in Mouse Dorsal Root Ganglion Neurons

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    Jamie K. Moy

    2018-02-01

    Full Text Available Plasticity in dorsal root ganglion (DRG neurons that promotes pain requires activity-dependent mRNA translation. Protein synthesis inhibitors block the ability of many pain-promoting molecules to enhance excitability in DRG neurons and attenuate behavioral signs of pain plasticity. In line with this, we have recently shown that phosphorylation of the 5′ cap-binding protein, eIF4E, plays a pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming. However, mRNA targets of eIF4E phosphorylation have not been elucidated in the DRG. Brain-derived neurotrophic factor (BDNF signaling from nociceptors in the DRG to spinal dorsal horn neurons is an important mediator of hyperalgesic priming. Regulatory mechanisms that promote pain plasticity via controlling BDNF expression that is involved in promoting pain plasticity have not been identified. We show that phosphorylation of eIF4E is paramount for Bdnf mRNA translation in the DRG. Bdnf mRNA translation is reduced in mice lacking eIF4E phosphorylation (eIF4ES209A and pro-nociceptive factors fail to increase BDNF protein levels in the DRGs of these mice despite robust upregulation of Bdnf-201 mRNA levels. Importantly, bypassing the DRG by giving intrathecal injection of BDNF in eIF4ES209A mice creates a strong hyperalgesic priming response that is normally absent or reduced in these mice. We conclude that eIF4E phosphorylation-mediated translational control of BDNF expression is a key mechanism for nociceptor plasticity leading to hyperalgesic priming.

  3. A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

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    Vargas-Alarcon Gilberto

    2012-02-01

    Full Text Available Abstract Background A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM; and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7 act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. Methods We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ. Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. Results The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036 mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88 than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002 and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001. Conclusion In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that

  4. Chronic Compression of the Dorsal Root Ganglion Enhances Mechanically Evoked Pain Behavior and the Activity of Cutaneous Nociceptors in Mice.

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    Tao Wang

    Full Text Available Radicular pain in humans is usually caused by intraforaminal stenosis and other diseases affecting the spinal nerve, root, or dorsal root ganglion (DRG. Previous studies discovered that a chronic compression of the DRG (CCD induced mechanical allodynia in rats and mice, with enhanced excitability of DRG neurons. We investigated whether CCD altered the pain-like behavior and also the responses of cutaneous nociceptors with unmyelinated axons (C-fibers to a normally aversive punctate mechanical stimulus delivered to the hairy skin of the hind limb of the mouse. The incidence of a foot shaking evoked by indentation of the dorsum of foot with an aversive von Frey filament (tip diameter 200 μm, bending force 20 mN was significantly higher in the foot ipsilateral to the CCD surgery as compared to the contralateral side on post-operative days 2 to 8. Mechanically-evoked action potentials were electrophysiologically recorded from the L3 DRG, in vivo, from cell bodies visually identified as expressing a transgenically labeled fluorescent marker (neurons expressing either the receptor MrgprA3 or MrgprD. After CCD, 26.7% of MrgprA3+ and 32.1% MrgprD+ neurons exhibited spontaneous activity (SA, while none of the unoperated control neurons had SA. MrgprA3+ and MrgprD+ neurons in the compressed DRG exhibited, in comparison with neurons from unoperated control mice, an increased response to the punctate mechanical stimuli for each force applied (6, 20, 40, and 80 mN. We conclude that CCD produced both a behavioral hyperalgesia and an enhanced response of cutaneous C-nociceptors to aversive punctate mechanical stimuli.

  5. Large dense-core vesicle exocytosis from mouse dorsal root ganglion neurons is regulated by neuropeptide Y.

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    Bost, Anneka; Shaib, Ali H; Schwarz, Yvonne; Niemeyer, Barbara A; Becherer, Ute

    2017-03-27

    Peptidergic dorsal root ganglion (DRG) neurons transmit sensory and nociceptive information from the periphery to the central nervous system. Their synaptic activity is profoundly affected by neuromodulatory peptides stored and released from large dense-core vesicles (LDCVs). However, the mechanism of peptide secretion from DRG neurons is poorly understood. Using total internal reflection fluorescence microscopy (TIRFM), we visualized individual LDCVs loaded with fluorescent neuropeptide Y (NPY) and analyzed their stimulation-dependent release. We tested several protocols and found an overall low stimulation-secretion coupling that increased after raising intracellular Ca 2+ concentration by applying a weak pre-stimulus. Interestingly, the stimulation protocol also influenced the mechanism of LDCV fusion. Depolarization of DRG neurons with a solution containing 60mM KCl triggered full fusion, kiss-and-run, and kiss-and-stay exocytosis with equal frequency. In contrast, field electrode stimulation primarily induced full fusion exocytosis. Finally, our results indicate that NPY can promote LDCV secretion. These results shed new light on the mechanism of NPY action during modulation of DRG neuron activity, an important pathway in the treatment of chronic pain. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors

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    Puopolo, Michelino; Martin-Eauclaire, Marie-France; Bean, Bruce P.

    2011-01-01

    The voltage-activated sodium (Nav) channel Nav1.9 is expressed in dorsal root ganglion (DRG) neurons where it is believed to play an important role in nociception. Progress in revealing the functional properties and pharmacological sensitivities of this non-canonical Nav channel has been slow because attempts to express this channel in a heterologous expression system have been unsuccessful. Here, we use a protein engineering approach to dissect the contributions of the four Nav1.9 voltage sensors to channel function and pharmacology. We define individual S3b–S4 paddle motifs within each voltage sensor, and show that they can sense changes in membrane voltage and drive voltage sensor activation when transplanted into voltage-activated potassium channels. We also find that the paddle motifs in Nav1.9 are targeted by animal toxins, and that these toxins alter Nav1.9-mediated currents in DRG neurons. Our results demonstrate that slowly activating and inactivating Nav1.9 channels have functional and pharmacological properties in common with canonical Nav channels, but also show distinctive pharmacological sensitivities that can potentially be exploited for developing novel treatments for pain. PMID:21670206

  7. Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia

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    Koenig, Jennifer; Werdehausen, Robert; Linley, John E.; Habib, Abdella M.; Vernon, Jeffrey; Lolignier, Stephane; Eijkelkamp, Niels; Zhao, Jing; Okorokov, Andrei L.; Woods, C. Geoffrey; Wood, John N.; Cox, James J.

    2015-01-01

    The Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conserved in humans and mice. The NAT has a similar tissue expression pattern to the sense gene and is alternatively spliced within dorsal root ganglia. The human and mouse NATs exist in cis with the sense gene in a tail-to-tail orientation and both share sequences that are complementary to the terminal exon of SCN9A/Scn9a. Overexpression analyses of the human NAT in human embryonic kidney (HEK293A) and human neuroblastoma (SH-SY5Y) cell lines show that it can function to downregulate Nav1.7 mRNA, protein levels and currents. The NAT may play an important role in regulating human pain thresholds and is a potential candidate gene for individuals with chronic pain disorders that map to the SCN9A locus, such as Inherited Primary Erythromelalgia, Paroxysmal Extreme Pain Disorder and Painful Small Fibre Neuropathy, but who do not contain mutations in the sense gene. Our results strongly suggest the SCN9A NAT as a prime candidate for new therapies based upon augmentation of existing antisense RNAs in the treatment of chronic pain conditions in man. PMID:26035178

  8. Phantom Remodeling Effect of Dorsal Root Entry Zone Lesioning in Phantom Limb Pain Caused by Brachial Plexus Avulsion.

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    Son, Byung-Chul; Ha, Sang-Woo

    2015-01-01

    Dorsal root entry zone (DREZ) lesioning has been reported to be effective for phantom limb pain caused by brachial plexus avulsion pain. Most reports on DREZ lesioning for brachial plexus avulsion pain have focused on the results of pain relief without a detailed description of phantom sensations following DREZ lesioning. Two patients (1 with amputation and the other nonamputated) with chronic intractable phantom limb pain caused by brachial plexus avulsion underwent DREZ lesioning on the avulsed segments of the cervical spinal cords. Changes of the phantom limb were observed. Immediately following DREZ lesioning, the phantom limb pain disappeared in the amputee, the phantom arm was shortened and the phantom hand disappeared. The other patient with the nonamputated arm reported an immediate 50% reduction in the size of the phantom hand, and pain relief was up to 70% of the preoperative phantom limb pain. There was no further change in the phantom arm and hand during the follow-up of 1.5-2 years. The phantom arms and hands showed a prompt shortening and reduction in size, rather than a disappearance, following successful DREZ lesioning in patients with chronic phantom limb pain caused by brachial plexus avulsion. © 2015 S. Karger AG, Basel.

  9. Channelrhodopsin-2-expressed dorsal root ganglion neurons activates calcium channel currents and increases action potential in spinal cord.

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    Zhang, Yi; Yue, Jing; Ai, Midan; Ji, Zhigang; Liu, Zhiguo; Cao, Xuehong; Li, Li

    2014-07-01

    We used optogenetic techniques in spinal cord and dorsal root ganglion (DRG) neuron studies. This study investigated changes in channelrhodopsin-2 (ChR2) expression in the spinal cord and DRG neurons using optogenetic techniques. The results show the possibility of using optogenetics to treat neuropathic pain. Previous studies have shown that activated ChR2 induces an increase in DRG neuron action potential. Western blot analysis was used to measure ChR2 protein levels in the spinal cord and DRG neurons or rats intrathecally injected with ChR2 lentivirus. Electrophysiology recording was used to detect differences in action potential levels in the spinal cord and calcium channel currents in the DRG neurons. Our studies showed that ChR2 expression increased the action potential in the spinal cord and increased calcium channel currents in DRG neurons. We successfully expressed the ChR2 protein in the spinal cord and DRG neurons. We also found that ChR2 increased the action potential in the spinal cord and activated the calcium channel in DRG neurons. These findings support the research possibilities of using optogenetic studies to improve treatment for neuropathic pain. N/A.

  10. Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes

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    Marc Parisien

    2017-05-01

    Full Text Available Dorsal root ganglia (DRG relay sensory information to the brain, giving rise to the perception of pain, disorders of which are prevalent and burdensome. Here, we mapped expression quantitative trait loci (eQTLs in a collection of human DRGs. DRG eQTLs were enriched within untranslated regions of coding genes of low abundance, with some overlapping with other brain regions and blood cell cis-eQTLs. We confirm functionality of identified eQTLs through their significant enrichment within open chromatin and highly deleterious SNPs, particularly at the exon level, suggesting substantial contribution of eQTLs to alternative splicing regulation. We illustrate pain-related genetic association results explained by DRG eQTLs, with the strongest evidence for contribution of the human leukocyte antigen (HLA locus, confirmed using a mouse inflammatory pain model. Finally, we show that DRG eQTLs are found among hits in numerous genome-wide association studies, suggesting that this dataset will help address pain components of non-pain disorders.

  11. Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters astrocyte metabolism and dorsal root ganglia neurite outgrowth

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    Schaub, Nicholas J.; Gilbert, Ryan J.

    2011-08-01

    Following central nervous system (CNS) injury, activated astrocytes form a glial scar that inhibits the migration of axons ultimately leading to regeneration failure. Biomaterials developed for CNS repair can provide local delivery of therapeutics and/or guidance mechanisms to encourage cell migration into damaged regions of the brain or spinal cord. Electrospun fibers are a promising type of biomaterial for CNS injury since these fibers can direct cellular and axonal migration while slowly delivering therapy to the injury site. In this study, it was hypothesized that inclusion of an anti-metabolite, 6-aminonicotinamide (6AN), within poly-l-lactic acid electrospun fibers could attenuate astrocyte metabolic activity while still directing axonal outgrowth. Electrospinning parameters were varied to produce highly aligned electrospun fibers that contained 10% or 20% (w/w) 6AN. 6AN release from the fiber substrates occurred continuously over 2 weeks. Astrocytes placed onto drug-releasing fibers were less active than those cultured on scaffolds without 6AN. Dorsal root ganglia placed onto control and drug-releasing scaffolds were able to direct neurites along the aligned fibers. However, neurite outgrowth was stunted by fibers that contained 20% 6AN. These results show that 6AN release from aligned, electrospun fibers can decrease astrocyte activity while still directing axonal outgrowth.

  12. Caspase-2 and microRNA34a/c regulate lidocaine-induced dorsal root ganglia apoptosis in vitro.

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    Li, Yandong; Jia, Zhi; Zhang, Laizhu; Wang, Jianguo; Yin, Guangming

    2015-11-15

    Epidural administration of lidocaine may cause neurotoxicity in spinal cord dorsal root ganglia neurons (DRGNs). In this study, we explored the underling mechanisms of apoptotic pathways of lidocaine-induced apoptosis in DRGNs. Neonatal rat DRGNs were treated with lidocaine to induced apoptosis in vitro. Western blot showed caspase- (casp-) 2/3/9 proteins were all upregulated by lidocaine in DRGNs. However, inhibition of casp-2 protected lidocaine-induced apoptosis in DRGNs, whereas Casp3/9 inhibition did not. The possible upstream epigenetic regulators of casp-2, microRNA-34 (miR-34) family, including miR-34a/b/c, were evaluated by dual-luciferase reporter assay and qRT-PCR. We found miR-34a/c, but not miR-34b, were down-regulated in lidocaine-induced DRGN apoptosis. Subsequent upregulation of miR-34 family showed miR-34a/c were able to inhibit casp-2 and protect lidocaine-induced apoptosis in DRGNs, whereas miR-34b did not. Thus, out study shows that casp-2, in association with miR-34a/c was actively involved in lidocaine-induced apoptosis in DRGNs. Inhibiting casp-2 or upregulating miR-34a/c may provide novel meanings to protect local anesthetic-induced neurotoxicity. Copyright © 2015. Published by Elsevier B.V.

  13. Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

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    Melemedjian Ohannes K

    2008-03-01

    Full Text Available Abstract 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 the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

  14. Localized and non-contact mechanical stimulation of dorsal root ganglion sensory neurons using scanning ion conductance microscopy.

    Science.gov (United States)

    Sánchez, Daniel; Anand, Uma; Gorelik, Julia; Benham, Christopher D; Bountra, Chas; Lab, Max; Klenerman, David; Birch, Rolfe; Anand, Praveen; Korchev, Yuri

    2007-01-15

    Mechanosensitive ion channels convert external mechanical force into electrical and chemical signals in cells, but their physiological function in different tissues is not clearly understood. One reason for this is that there is as yet no satisfactory physiological method to stimulate these channels in living cells. Using the nanopipette-probe of the Scanning Ion Conductance Microscope (SICM), we have developed a new technique to apply local mechanical stimulus to living cells to an area of about 0.385 microm2, determined by the pipette diameter. Our method prevents any physical contact and damage to the cell membrane by use of a pressure jet applied via the nanopipette. The study used whole-cell patch-clamp recordings and measurements of intracellular Ca2+ concentration to validate the application of the mechanical stimulation protocols in human and rat dorsal root ganglia (DRG) sensory neurons. We were able, for the first time, to produce a non-contact, controlled mechanical stimulation on living neurites of human DRG neurons. Our methods will enable the identification and characterisation of compounds being developed for the treatment of clinical mechanical hypersensitivity states.

  15. Abnormalities in spinal neurons and dorsal root ganglion cells in Tangier disease presenting with a syringomyelia-like syndrome.

    Science.gov (United States)

    Schmalbruch, H; Stender, S; Boysen, G

    1987-09-01

    A woman with homozygous Tangier disease had progressive syringomyelia-like neuropathy. She died with cardiac failure at age 61. A sural nerve biopsy taken at age 60 had shown lipid storage in Schwann and interstitial cells, and a pronounced loss of unmyelinated fibers. The neurons of the L5 spinal ganglion and, to a lesser extent, all neurons of the sacral spinal cord, contained large lipid inclusions which in electron micrographs differed from those in Schwann and satellite cells. There was no storage material in glial cells. The neuronal inclusions were membrane-bound and consisted of electron-dense and electron-lucent components. There was evidence of neuronal death in the spinal ganglion, and a diameter histogram showed that small cytons had preferentially been lost. The inclusions probably were secondary lysosomes or residual bodies, and resembled giant lipofuscin granules. Nevertheless, they were uncolored and displayed weak autofluorescence as compared to the aging pigment in control ganglia. It is tentatively suggested that the syringomyelia-like neuropathy in Tangier disease represents a lysosomal storage disorder preferentially affecting small dorsal root ganglion cells.

  16. Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors.

    Science.gov (United States)

    Bosmans, Frank; Puopolo, Michelino; Martin-Eauclaire, Marie-France; Bean, Bruce P; Swartz, Kenton J

    2011-07-01

    The voltage-activated sodium (Nav) channel Nav1.9 is expressed in dorsal root ganglion (DRG) neurons where it is believed to play an important role in nociception. Progress in revealing the functional properties and pharmacological sensitivities of this non-canonical Nav channel has been slow because attempts to express this channel in a heterologous expression system have been unsuccessful. Here, we use a protein engineering approach to dissect the contributions of the four Nav1.9 voltage sensors to channel function and pharmacology. We define individual S3b-S4 paddle motifs within each voltage sensor, and show that they can sense changes in membrane voltage and drive voltage sensor activation when transplanted into voltage-activated potassium channels. We also find that the paddle motifs in Nav1.9 are targeted by animal toxins, and that these toxins alter Nav1.9-mediated currents in DRG neurons. Our results demonstrate that slowly activating and inactivating Nav1.9 channels have functional and pharmacological properties in common with canonical Nav channels, but also show distinctive pharmacological sensitivities that can potentially be exploited for developing novel treatments for pain.

  17. Atopic keratinocytes induce increased neurite outgrowth in a coculture model of porcine dorsal root ganglia neurons and human skin cells.

    Science.gov (United States)

    Roggenkamp, Dennis; Falkner, Susanne; Stäb, Franz; Petersen, Marlen; Schmelz, Martin; Neufang, Gitta

    2012-07-01

    Skin of patients suffering from atopic eczema displays a higher epidermal nerve fiber density, associated with neurogenic inflammation and pruritus. Using an in vitro coculture system, allowing a spatially compartmented culture of somata from porcine dorsal root ganglion neurons and human primary skin cells, we investigated the influence of dermal fibroblasts and keratinocytes on neurite outgrowth. In comparison with dermal fibroblasts, keratinocytes induced more branched and less calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers. By adding neutralizing antibodies, we showed that nerve growth factor (NGF) and glial cell-line-derived neurotrophic factor (GDNF) are pivotal neurotrophic factors of skin cell-induced neurite outgrowth. Keratinocytes and dermal fibroblasts secreted different ratios of neurotrophic factors, influencing morphology and CGRP immunoreactivity of neurites. To investigate changes of the peripheral nervous system in the pathogenesis of atopic eczema in vitro, we analyzed neurite outgrowth mediated by atopic skin cells. Atopic keratinocytes produced elevated levels of NGF and mediated an increased outgrowth of CGRP-positive sensory fibers. Our results demonstrate the impact of dermal fibroblasts and keratinocytes on skin innervation and emphasize the role of keratinocytes as key players of hyperinnervation in atopic eczema.

  18. Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

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    Bruns, Tim M.; Wagenaar, Joost B.; Bauman, Matthew J.; Gaunt, Robert A.; Weber, Douglas J.

    2013-04-01

    Objective. Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach. We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results. Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance. This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability.

  19. One cell model establishment to inhibit CaMKIIγ mRNA expression in the dorsal root ganglion neuron by RNA interfere.

    Science.gov (United States)

    Wen, Xianjie; Li, Xiaohong; Liang, Hua; Yang, Chenxiang; Zhong, Jiying; Wang, Hanbing; Liu, Hongzhen

    2017-09-01

    CaMKIIγ in dorsal root ganglion neurons is closely related to the neuropathic pain, neuron injury induced by local anesthetics. To get great insight into the function of CaMKIIγ in dorsal root ganglion neurons, we need one cell model to specially inhibit the CaMKIIγ mRNA expression. The present study was aimed to establish one cell model to specially inhibit the CaMKIIγ mRNA expression. We designed the CaMKIIγ shRNA sequence and connected with pYr-1.1 plasmid. The ligation product of the CaMKIIγshRNA and pYr-1.1 plasmid was recombined with pAd/PL-DEST vector into pAD-CaMKIIγ-shRNA. adenovirus vector. pAD-CaMKIIγ-shRNA. adenovirus vector infected the dorsal root ganglion neuron to inhibit the CaMKIIγ mRNA expression in vitro. The pAD-CaMKIIγ-shRNA adenovirus vector was verified to be correct by the digestion, sequence. And pAD-CaMKIIγ-shRNA. adenovirus vector can infect the DRG cells to inhibit the CaMKIIγ mRNA or protein expression by the real-time polymerase chain reaction (PCR) or western blotting. Those results showed that we successfully constructed one adenovirus vector that can infect the dorsal root ganglion neuron to inhibit the CaMKIIγ mRNA and protein expression. That will supply with one cell model for the CaMKIIγ function study.

  20. [Effect of Triptolide on expression of NMDAR1 and BSI-B4 binding sites in spinal dorsal horn and dorsal root ganglion in rats with adjuvant arthritis].

    Science.gov (United States)

    Wei, Yun-bo; Lin, Rong; Chen, Wei; Zhang, Xu-dong; Lu, Zhuo-hui; Jiang, Wen-wen; Wei, Deng-ming

    2014-11-01

    To study the analgesic effect of Triptolide(TP) in rats with adjuvant and the possible mechanism. Fifty healthy SD rats were randomly divided into normal control group (group A), model group (group B), and low(group C), middle (group D) and high(group E) dose TP treatment groups. Except the group A, each group of rats were reared by toe intradermal injection of 0. 1 mL Freund's complete adjuvant. After 14 days,rats in the C, D and E groups were taken different doses (0. 1 mg/kg group C, 0. 2mg/kg group D, and 0. 4 mg/kg group E) by intraperitoneal injection of TP for 9 days, and then thermal withdrawal latency and the expression of NMDAR1 and BSI-B4 binding sites in lumbar5 (L5) spinal dorsal horn and DRG were detected. Thermal withdrawal latency of rats in group B was significantly lower than that of group A (P effect relationship; NMDAR-1 and BSI-B4 binding sites expression levels were significantly increased in group B than those in group A (P effect of TP is related to reducing levels of expression of NMDAR1 and BSI-B4 binding sites in spinal dorsal horn and DRG in rats with adjuvant arthritis.

  1. Clinical significance of the position of dorsal root ganglia in degenerative lumbar diseases. Correlation between anatomic study and imaging study with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Masahiro; Kikuchi, Tomiichi [Fukushima Medical Coll., Matsuoka (Japan)

    1995-06-01

    In order to estimate the ralationship between the position of dorsal root ganglia (DRG) and radicular symptoms, anatomical study was done on 81 cadavers, and a clinical study with MRI was done on 20 cases of lumbar disc herniation and 20 of lumbar spondylosis with L{sub 5} radiculopathy. The position of DRG is not related to the occurrence of radicular symptoms in disc herniation, while in lumbar spondylosis proximally placed DRG are related to both of unilateral and bilateral occurrence of redicular symptoms. Unilateral occurrence of radicular symptoms is influenced by surrounding tissues of the nerve root, rather than the position of DRG. (author).

  2. Dopamine modulation of transient receptor potential vanilloid type 1 (TRPV1) receptor in dorsal root ganglia neurons.

    Science.gov (United States)

    Chakraborty, Saikat; Rebecchi, Mario; Kaczocha, Martin; Puopolo, Michelino

    2016-03-15

    The transient receptor potential vanilloid type 1 (TRPV1) receptor plays a key role in the modulation of nociceptor excitability. To address whether dopamine can modulate the activity of TRPV1 channels in nociceptive neurons, the effects of dopamine and dopamine receptor agonists were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons. Dopamine or SKF 81297 (an agonist at D1/D5 receptors), caused inhibition of both inward and outward currents by ∼60% and ∼48%, respectively. The effect of SKF 81297 was reversed by SCH 23390 (an antagonist at D1/D5 receptors), confirming that it was mediated by activation of D1/D5 dopamine receptors. In contrast, quinpirole (an agonist at D2 receptors) had no significant effect on the capsaicin-activated current. Inhibition of the capsaicin-activated current by SKF 81297 was mediated by G protein coupled receptors (GPCRs), and highly dependent on external calcium. The inhibitory effect of SKF 81297 on the capsaicin-activated current was not affected when the protein kinase A (PKA) activity was blocked with H89, or when the protein kinase C (PKC) activity was blocked with bisindolylmaleimide II (BIM). In contrast, when the calcium-calmodulin-dependent protein kinase II (CaMKII) was blocked with KN-93, the inhibitory effect of SKF 81297 on the capsaicin-activated current was greatly reduced, suggesting that activation of D1/D5 dopamine receptors may be preferentially linked to CaMKII activity. We suggest that modulation of TRPV1 channels by dopamine in nociceptive neurons may represent a way for dopamine to modulate incoming noxious stimuli. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  3. Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats.

    Science.gov (United States)

    Hu, Shufen; Xiao, Ying; Zhu, Liyan; Li, Lin; Hu, Chuang-Ying; Jiang, Xinghong; Xu, Guang-Yin

    2013-02-15

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain in association with altered bowel movements. The underlying mechanisms of visceral hypersensitivity remain elusive. This study was designed to examine the role for sodium channels in a rat model of chronic visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch-clamp configurations. The expression of Na(V)1.8 was analyzed by Western blot and quantitative real-time PCR. NMD significantly increased AWR scores, which lasted for ~6 wk in an association with hyperexcitability of colon DRG neurons. TTX-resistant but not TTX-sensitive sodium current density was greatly enhanced in colon DRG neurons in NMD rats. Compared with controls, activation curves showed a leftward shift in NMD rats whereas inactivation curves did not differ significantly. NMD markedly accelerated the activation time of peak current amplitude without any changes in inactivation time. Furthermore, NMD remarkably enhanced expression of Na(V)1.8 at protein levels but not at mRNA levels in colon-related DRGs. The expression of Na(V)1.9 was not altered after NMD. These data suggest that NMD enhances TTX-resistant sodium activity of colon DRG neurons, which is most likely mediated by a leftward shift of activation curve and by enhanced expression of Na(V)1.8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS.

  4. Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro.

    Science.gov (United States)

    Doan, Lisa V; Eydlin, Olga; Piskoun, Boris; Kline, Richard P; Recio-Pinto, Esperanza; Rosenberg, Andrew D; Blanck, Thomas J J; Xu, Fang

    2014-01-01

    Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action of local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, the authors examined whether there were any differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. The mean KCl-induced calcium transient was greater in P7 neurons (P lidocaine significantly inhibited KCl-induced calcium responses in both ages (P lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly, cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses.

  5. Enhanced Expression of TREK-1 Is Related with Chronic Constriction Injury of Neuropathic Pain Mouse Model in Dorsal Root Ganglion.

    Science.gov (United States)

    Han, Hyo Jo; Lee, Seung Wook; Kim, Gyu-Tae; Kim, Eun-Jin; Kwon, Byeonghun; Kang, Dawon; Kim, Hyun Jeong; Seo, Kwang-Suk

    2016-05-01

    Neuropathic pain is a complex state showing increased pain response with dysfunctional inhibitory neurotransmission. The TREK family, one of the two pore domain K⁺ (K2P) channel subgroups were focused among various mechanisms of neuropathic pain. These channels influence neuronal excitability and are thought to be related in mechano/thermosensation. However, only a little is known about the expression and role of TREK-1 and TREK-2, in neuropathic pain. It is performed to know whether TREK-1 and/ or 2 are positively related in dorsal root ganglion (DRG) of a mouse neuropathic pain model, the chronic constriction injury (CCI) model. Following this purpose, Reverse Transcription Polymerase Chain Reaction (RT-PCR) and western blot analyses were performed using mouse DRG of CCI model and compared to the sham surgery group. Immunofluorescence staining of isolectin- B4 (IB4) and TREK were performed. Electrophysiological recordings of single channel currents were analyzed to obtain the information about the channel. Interactions with known TREK activators were tested to confirm the expression. While both TREK-1 and TREK-2 mRNA were significantly overexpressed in DRG of CCI mice, only TREK-1 showed significant increase (~9 fold) in western blot analysis. The TREK-1-like channel recorded in DRG neurons of the CCI mouse showed similar current-voltage relationship and conductance to TREK-1. It was easily activated by low pH solution (pH 6.3), negative pressure, and riluzole. Immunofluorescence images showed the expression of TREK-1 was stronger compared to TREK-2 on IB4 positive neurons. These results suggest that modulation of the TREK-1 channel may have beneficial analgesic effects in neuropathic pain patients.

  6. Motoneuron development influences dorsal root ganglia survival and Schwann cell development in a vertebrate model of spinal muscular atrophy.

    Science.gov (United States)

    Hao, Le Thi; Duy, Phan Q; Jontes, James D; Beattie, Christine E

    2015-01-15

    Low levels of the survival motor neuron protein (SMN) cause the disease spinal muscular atrophy. A primary characteristic of this disease is motoneuron dysfunction and paralysis. Understanding why motoneurons are affected by low levels of SMN will lend insight into this disease and to motoneuron biology in general. Motoneurons in zebrafish smn mutants develop abnormally; however, it is unclear where Smn is needed for motoneuron development since it is a ubiquitously expressed protein. We have addressed this issue by expressing human SMN in motoneurons in zebrafish maternal-zygotic (mz) smn mutants. First, we demonstrate that SMN is present in axons, but only during the period of robust motor axon outgrowth. We also conclusively demonstrate that SMN acts cell autonomously in motoneurons for proper motoneuron development. This includes the formation of both axonal and dendritic branches. Analysis of the peripheral nervous system revealed that Schwann cells and dorsal root ganglia (DRG) neurons developed abnormally in mz-smn mutants. Schwann cells did not wrap axons tightly and had expanded nodes of Ranvier. The majority of DRG neurons had abnormally short peripheral axons and later many of them failed to divide and died. Expressing SMN just in motoneurons rescued both of these cell types showing that their failure to develop was secondary to the developmental defects in motoneurons. Driving SMN just in motoneurons did not increase survival of the animal, suggesting that SMN is needed for motoneuron development and motor circuitry, but that SMN in other cells types factors into survival. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Despite Differences in Cytosolic Calcium Regulation, Lidocaine Toxicity Is Similar in Adult and Neonatal Rat Dorsal Root Ganglia in Vitro

    Science.gov (United States)

    Doan, Lisa V.; Eydlin, Olga; Piskoun, Boris; Kline, Richard P; Recio-Pinto, Esperanza; Rosenberg, Andrew D; Blanck, Thomas JJ; Xu, Fang

    2013-01-01

    Background Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action for local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, we examined whether there were differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. Methods DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. Results The mean KCl-induced calcium transient was greater in P7 neurons (p lidocaine significantly inhibited KCl-induced calcium responses in both ages (p lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Conclusions Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses. PMID:23851347

  8. Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

    Science.gov (United States)

    Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

    2015-04-01

    Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

  9. Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

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    Huang Li-Yen

    2007-08-01

    Full Text Available Abstract Prostaglandin E2 (PGE2 is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

  10. Quantitative Analysis of Rat Dorsal Root Ganglion Neurons Cultured on Microelectrode Arrays Based on Fluorescence Microscopy Image Processing.

    Science.gov (United States)

    Mari, João Fernando; Saito, José Hiroki; Neves, Amanda Ferreira; Lotufo, Celina Monteiro da Cruz; Destro-Filho, João-Batista; Nicoletti, Maria do Carmo

    2015-12-01

    Microelectrode Arrays (MEA) are devices for long term electrophysiological recording of extracellular spontaneous or evocated activities on in vitro neuron culture. This work proposes and develops a framework for quantitative and morphological analysis of neuron cultures on MEAs, by processing their corresponding images, acquired by fluorescence microscopy. The neurons are segmented from the fluorescence channel images using a combination of segmentation by thresholding, watershed transform, and object classification. The positioning of microelectrodes is obtained from the transmitted light channel images using the circular Hough transform. The proposed method was applied to images of dissociated culture of rat dorsal root ganglion (DRG) neuronal cells. The morphological and topological quantitative analysis carried out produced information regarding the state of culture, such as population count, neuron-to-neuron and neuron-to-microelectrode distances, soma morphologies, neuron sizes, neuron and microelectrode spatial distributions. Most of the analysis of microscopy images taken from neuronal cultures on MEA only consider simple qualitative analysis. Also, the proposed framework aims to standardize the image processing and to compute quantitative useful measures for integrated image-signal studies and further computational simulations. As results show, the implemented microelectrode identification method is robust and so are the implemented neuron segmentation and classification one (with a correct segmentation rate up to 84%). The quantitative information retrieved by the method is highly relevant to assist the integrated signal-image study of recorded electrophysiological signals as well as the physical aspects of the neuron culture on MEA. Although the experiments deal with DRG cell images, cortical and hippocampal cell images could also be processed with small adjustments in the image processing parameter estimation.

  11. Effects of selenium on calcium signaling and apoptosis in rat dorsal root ganglion neurons induced by oxidative stress.

    Science.gov (United States)

    Uğuz, Abdülhadi Cihangir; Nazıroğlu, Mustafa

    2012-08-01

    Ca(2+) is well known for its role as crucial second messenger in modulating many cellular physiological functions, Ca(2+) overload is detrimental to cellular function and may present as an important cause of cellular oxidative stress generation and apoptosis. The aim of this study is to investigate the effects of selenium on lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), cytosolic Ca(2+) release, cell viability (MTT) and apoptosis values in dorsal root ganglion (DRG) sensory neurons of rats. DRG cells were divided into four groups namely control, H(2)O(2) (as a model substance used as a paradigm for oxidative stress), selenium, selenium + H(2)O(2). Moderate doses and times of H(2)O(2) and selenium were determined by MTT test. Cells were preterated 200 nM selenium for 30 h before incubatation with 1 μM H(2)O(2) for 2 h. Lipid peroxidation levels were lower in the control, selenium, selenium + H(2)O(2) groups than in the H(2)O(2) group. GSH-Px activities were higher in the selenium groups than in the H(2)O(2) group. GSH levels were higher in the control, selenium, selenium + H(2)O(2) groups than in the H(2)O(2) group. Cytosolic Ca(2+) release was higher in the H(2)O(2) group than in the control, selenium, selenium + H(2)O(2) groups. Cytosolic Ca(2+) release was lower in the selenium + H(2)O(2) group than in the H(2)O(2). In conclusion, the present study demonstrates that selenium induced protective effects on oxidative stress, [Ca(2+)](c) release and apoptosis in DRG cells. Since selenium deficiency is a common feature of oxidative stress-induced neurological diseases of sensory neurons, our findings are relevant to the etiology of pathology in oxidative stress-induced neurological diseases of the DRG neurons.

  12. Altered expression of sodium channel distribution in the dorsal root ganglion after gradual elongation of rat sciatic nerves.

    Science.gov (United States)

    Ohno, Katsunori; Yokota, Atsushi; Hirofuji, Shinji; Kanbara, Kiyoto; Ohtsuka, Hisashi; Kinoshita, Mitsuo

    2010-04-01

    To elucidate the pathophysiological mechanisms underlying chronic nerve-stretch injury, we gradually lengthened rat femurs by 15 mm at the rate of 0.5 mm/day (group L, n = 13). The control groups comprised sham-operated (group S, n = 10) and naive (group N, n = 8) rats. Immediately after the lengthening, we performed a conduction study on their sciatic nerves and harvested samples. Electrophysiological and histological analyses showed mild conduction slowing and axonal degeneration of unmyelinated fibers in group L rats. Altered mRNA expression of the voltage-gated sodium channels in the dorsal root ganglion was also observed. Tetrodotoxin-resistant (TTX-R) sodium-channel Nav1.8 mRNA expression was significantly decreased and TTX-R sodium-channel Nav1.9 mRNA expression showed a tendency to decrease when compared with the mRNA expressions in the control groups. However, tetrodotoxin-sensitive (TTX-S) sodium-channel Nav1.3 mRNA expression remained unaltered. The immunohistochemical alteration of Nav1.8 protein expression was parallel to the results of the mRNA expression. Previous studies involving neuropathic states have suggested that pain/paresthesia is modulated by a subset of sodium channels, including downregulation and/or upregulation of TTX-R and TTX-S sodium channels, respectively. Our findings indicate that Nav1.8 downregulation may be one of the pathophysiological mechanisms involved in limb lengthening-induced neuropathy.

  13. Expression of the immunoglobulin superfamily cell adhesion molecules in the developing spinal cord and dorsal root ganglion.

    Science.gov (United States)

    Gu, Zirong; Imai, Fumiyasu; Kim, In Jung; Fujita, Hiroko; Katayama, Kei ichi; Mori, Kensaku; Yoshihara, Yoshihiro; Yoshida, Yutaka

    2015-01-01

    Cell adhesion molecules belonging to the immunoglobulin superfamily (IgSF) control synaptic specificity through hetero- or homophilic interactions in different regions of the nervous system. In the developing spinal cord, monosynaptic connections of exquisite specificity form between proprioceptive sensory neurons and motor neurons, however, it is not known whether IgSF molecules participate in regulating this process. To determine whether IgSF molecules influence the establishment of synaptic specificity in sensory-motor circuits, we examined the expression of 157 IgSF genes in the developing dorsal root ganglion (DRG) and spinal cord by in situ hybridization assays. We find that many IgSF genes are expressed by sensory and motor neurons in the mouse developing DRG and spinal cord. For instance, Alcam, Mcam, and Ocam are expressed by a subset of motor neurons in the ventral spinal cord. Further analyses show that Ocam is expressed by obturator but not quadriceps motor neurons, suggesting that Ocam may regulate sensory-motor specificity in these sensory-motor reflex arcs. Electrophysiological analysis shows no obvious defects in synaptic specificity of monosynaptic sensory-motor connections involving obturator and quadriceps motor neurons in Ocam mutant mice. Since a subset of Ocam+ motor neurons also express Alcam, Alcam or other functionally redundant IgSF molecules may compensate for Ocam in controlling sensory-motor specificity. Taken together, these results reveal that IgSF molecules are broadly expressed by sensory and motor neurons during development, and that Ocam and other IgSF molecules may have redundant functions in controlling the specificity of sensory-motor circuits.

  14. Expression of the immunoglobulin superfamily cell adhesion molecules in the developing spinal cord and dorsal root ganglion.

    Directory of Open Access Journals (Sweden)

    Zirong Gu

    Full Text Available Cell adhesion molecules belonging to the immunoglobulin superfamily (IgSF control synaptic specificity through hetero- or homophilic interactions in different regions of the nervous system. In the developing spinal cord, monosynaptic connections of exquisite specificity form between proprioceptive sensory neurons and motor neurons, however, it is not known whether IgSF molecules participate in regulating this process. To determine whether IgSF molecules influence the establishment of synaptic specificity in sensory-motor circuits, we examined the expression of 157 IgSF genes in the developing dorsal root ganglion (DRG and spinal cord by in situ hybridization assays. We find that many IgSF genes are expressed by sensory and motor neurons in the mouse developing DRG and spinal cord. For instance, Alcam, Mcam, and Ocam are expressed by a subset of motor neurons in the ventral spinal cord. Further analyses show that Ocam is expressed by obturator but not quadriceps motor neurons, suggesting that Ocam may regulate sensory-motor specificity in these sensory-motor reflex arcs. Electrophysiological analysis shows no obvious defects in synaptic specificity of monosynaptic sensory-motor connections involving obturator and quadriceps motor neurons in Ocam mutant mice. Since a subset of Ocam+ motor neurons also express Alcam, Alcam or other functionally redundant IgSF molecules may compensate for Ocam in controlling sensory-motor specificity. Taken together, these results reveal that IgSF molecules are broadly expressed by sensory and motor neurons during development, and that Ocam and other IgSF molecules may have redundant functions in controlling the specificity of sensory-motor circuits.

  15. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

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    Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

    2016-01-01

    Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure.

  16. Global diffuse distribution in the brain and efficient gene delivery to the dorsal root ganglia by intrathecal injection of adeno-associated viral vector serotype 1.

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    Iwamoto, Naotaka; Watanabe, Atsushi; Yamamoto, Motoko; Miyake, Noriko; Kurai, Toshiyuki; Teramoto, Akira; Shimada, Takashi

    2009-06-01

    The success of gene therapy for inherited neurodegenerative diseases such as metachromatic leukodystrophy (MLD) depends on the development of efficient gene delivery throughout the brain guarded by the blood-brain barrier and achieves distribution of the deficient enzyme throughout the brain. Direct injection of viral vector into the brain parenchyma is too invasive and may not be sufficient to treat the entire brain. As an alternative approach, we examined the feasibility of intrathecal (IT) injection of adeno-associated viral vector serotype 1 (AAV1). AAV1 vector expressing arylsulfatase A (ASA) and green fluorescence protein (GFP) was intrathecally injected into ASA knockout MLD model mice. Expression of GFP was assessed by fluorescence microscopy and immunohistochemical methods, whereas the concentration of ASA was determined by a quantitative enzyme-linked immunosorbent assay. Broad distribution of GFP expression was seen throughout the brain after IT injection of AAV1 vector. In addition, a large number of nerve fibers in the dorsal spinal cord and many neural cell bodies in the dorsal root ganglia were efficiently transduced. Widespread distribution of ASA activity and a significant reduction of sulfatide content were confirmed in treated MLD model mice. IT injection of AAV1 vector is a useful and non-invasive method for widespread gene delivery to the brain and dorsal root ganglia. (c) 2009 John Wiley & Sons, Ltd.

  17. Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by μ-conotoxins.

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    Zhang, Min-Min; Wilson, Michael J; Gajewiak, Joanna; Rivier, Jean E; Bulaj, Grzegorz; Olivera, Baldomero M; Yoshikami, Doju

    2013-05-01

    Adult rat dorsal root ganglion (DRG) neurons normally express transcripts for five isoforms of the α-subunit of voltage-gated sodium channels: NaV 1.1, 1.6, 1.7, 1.8 and 1.9. Tetrodotoxin (TTX) readily blocks all but NaV 1.8 and 1.9, and pharmacological agents that discriminate among the TTX-sensitive NaV 1-isoforms are scarce. Recently, we used the activity profile of a panel of μ-conotoxins in blocking cloned rodent NaV 1-isoforms expressed in Xenopus laevis oocytes to conclude that action potentials of A- and C-fibres in rat sciatic nerve were, respectively, mediated primarily by NaV 1.6 and NaV 1.7. We used three μ-conotoxins, μ-TIIIA, μ-PIIIA and μ-SmIIIA, applied individually and in combinations, to pharmacologically differentiate the TTX-sensitive INa of voltage-clamped neurons acutely dissociated from adult rat DRG. We examined only small and large neurons whose respective INa were >50% and >80% TTX-sensitive. In both small and large neurons, the ability of the toxins to block TTX-sensitive INa was μ-TIIIA NaV 1-isoforms, co-expressed with various NaV β-subunits in X. laevis oocytes, were consistent: NaV 1.1, 1.6 and 1.7 could account for all of the TTX-sensitive INa , with NaV 1.1 NaV 1.6 NaV 1.7 for small neurons and NaV 1.7 NaV 1.1 NaV 1.6 for large neurons. Combinations of μ-conotoxins can be used to determine the probable NaV 1-isoforms underlying the INa in DRG neurons. Preliminary experiments with sympathetic neurons suggest that this approach is extendable to other neurons. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  18. [Effects of Electroacupuncture on Activities of Satellite Glial Cells of Dorsal Root Ganglia in Rats with Neck Incision Pain].

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    Qiao, Li-Na; Tan, Lian-Hong; Yang, Jiao-Jiao; Gao, Qiao-Ling; Zhu, Jiang; Rong, Pei-Jing; Zhu, Bing; Yang, Yong-Sheng; Liu, Jun-Ling

    2017-08-25

    To observe the effect of electroacupuncture (EA) stimulation of "Futu"(LI 18), etc. on activities of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) in rats with neck-incision pain so as to explore its mechanism underlying reduction of post-surgical pain of thyroidectomy. Male SD rats were randomly divided into control, model, EA-Futu (LI 18), EA-Hegu (LI 4)-Neiguan (PC 6), and EA-Zusanli (ST 36)-Yanglingquan (GB 34) groups, with 20 rats in each group. The neck-incision pain model was established by making a longitudinal incision and repeated mechanical stimulation. In the EA-LI 18, EA-LI 4-PC 6 and EA-ST 36-GB 34 groups, EA stimulation was administrated for 30 min, once a day,continuously for 3 days. The thermal pain threshold (PT) of the neck-incision region was detected. The immunoactivity of glial fibrillary acidic protein (GFAP,a specific marker for SGCs) and connexin 43 (Cx 43) of DRGs (C 2-C 6) was determined by fluorescent immunohistochemistry. The expression levels of GFAP, IL-1 β, IL-6, and TNF-α mRNAs were determined by quantitative Real-time PCR, and the contents of IL-1 β,IL-6,TNF-α assayed by enzyme linked immunosorbent assay (ELISA) and the expression of Cx 43 protein was detected by Western blot. After EA intervention at LI 18 and LI 4-PC 6 (but not ST 36-GB 34), neck incision-induced reduction of the thermal PT was obviously prolonged in comparison with the model group (PGB 34 group except the down-regulated IL-1 β and TNF-α mRNAs, in the contents of IL-1 β and TNF-α of the EA-LI 4-PC 6 group, and in the IL-6 content of the EA-LI 18 group (P>0.05). EA stimulation of LI 18 and LI 4-PC 6 can significantly suppress pain reaction of neck incision in the rat, which is closely associated with its effects in down-regulating the activity of SGCs, decreasing the release of pro-inflammatory cytokines and in weakening the expression of Cx 43 in the cervical DRGs.

  19. Kv4 channels underlie the subthreshold-operating A-type K+-current in nociceptive dorsal root ganglion neurons

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    Thanawath R Na Phuket

    2009-07-01

    Full Text Available 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 molecular correlate of the corresponding A-type K+ current (IA has remained hypothetical.  Kv4 channels may underlie the IA in DRG neurons.  We combined electrophysiology, molecular biology (whole-tissue and single-cell RT-PCR and immunohistochemistry to investigate the molecular basis of the IA in acutely dissociated DRG neurons from 7-8 day-old rats.  Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM and 4-aminopyridine-sensitive (5 mM IA.  Matching Kv4 channel properties, activation and inactivation of this IA occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent.  Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs.  Also, single small-medium diameter DRG neurons (~30 mm exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker.  In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent.  Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2.  Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to IA in DRG neurons.  Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons.

  20. α-Conotoxin Vc1.1 inhibits human dorsal root ganglion neuroexcitability and mouse colonic nociception via GABAB receptors.

    Science.gov (United States)

    Castro, Joel; Harrington, Andrea M; Garcia-Caraballo, Sonia; Maddern, Jessica; Grundy, Luke; Zhang, Jingming; Page, Guy; Miller, Paul E; Craik, David J; Adams, David J; Brierley, Stuart M

    2017-06-01

    α-Conotoxin Vc1.1 is a small disulfide-bonded peptide from the venom of the marine cone snail Conus victoriae. Vc1.1 has antinociceptive actions in animal models of neuropathic pain, but its applicability to inhibiting human dorsal root ganglion (DRG) neuroexcitability and reducing chronic visceral pain (CVP) is unknown. We determined the inhibitory actions of Vc1.1 on human DRG neurons and on mouse colonic sensory afferents in healthy and chronic visceral hypersensitivity (CVH) states. In mice, visceral nociception was assessed by neuronal activation within the spinal cord in response to noxious colorectal distension (CRD). Quantitative-reverse-transcription-PCR, single-cell-reverse-transcription-PCR and immunohistochemistry determined γ-aminobutyric acid receptor B (GABABR) and voltage-gated calcium channel (CaV2.2, CaV2.3) expression in human and mouse DRG neurons. Vc1.1 reduced the excitability of human DRG neurons, whereas a synthetic Vc1.1 analogue that is inactive at GABABR did not. Human DRG neurons expressed GABABR and its downstream effector channels CaV2.2 and CaV2.3. Mouse colonic DRG neurons exhibited high GABABR, CaV2.2 and CaV2.3 expression, with upregulation of the CaV2.2 exon-37a variant during CVH. Vc1.1 inhibited mouse colonic afferents ex vivo and nociceptive signalling of noxious CRD into the spinal cord in vivo, with greatest efficacy observed during CVH. A selective GABABR antagonist prevented Vc1.1-induced inhibition, whereas blocking both CaV2.2 and CaV2.3 caused inhibition comparable with Vc1.1 alone. Vc1.1-mediated activation of GABABR is a novel mechanism for reducing the excitability of human DRG neurons. Vc1.1-induced activation of GABABR on the peripheral endings of colonic afferents reduces nociceptive signalling. The enhanced antinociceptive actions of Vc1.1 during CVH suggest it is a novel candidate for the treatment for CVP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  1. Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue

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    Ip Virginia

    2010-09-01

    Full Text Available Abstract Background ATP7A, 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 tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg or drug vehicle twice weekly for 8 weeks. Results In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H. High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals. Conclusions In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non

  2. The distribution of kisspeptin and its receptor GPR54 in rat dorsal root ganglion and up-regulation of its expression after CFA injection.

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    Mi, Wen-Li; Mao-Ying, Qi-Liang; Liu, Qiong; Wang, Xiao-Wei; Li, Xiu; Wang, Yan-Qing; Wu, Gen-Cheng

    2009-03-16

    Kisspeptin/GPR54 system plays a crucial role in the control of puberty onset and reproductive function. In the present study, we gave the first report that kisspeptin and GPR54 were expressed in the small- to large-sized neurons, and co-localized with Bandeiraea simplicifolia isolectin B4 (IB4), calcitonin-gene-related peptide (CGRP) and neurofilament 200 (NF200) in the L4/5 dorsal root ganglion (DRG) of naïve rats, detected by the double immunofluorescent staining. Interestingly, a marked elevation in the levels of KiSS-1 and GPR54 mRNA as well as protein was observed in the spinal dorsal horn and DRG 4 and 14 days following intra-articular injection of complete Freund's adjuvant (CFA), indicating a possible involvement of the kisspeptin/GPR54 system in chronic inflammatory pain.

  3. Assessing the effectiveness of ‘pulse radiofrequency treatment of dorsal root ganglion’ in patients with chronic lumbar radicular pain: study protocol for a randomized control trial

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    Shanthanna Harsha

    2012-04-01

    Full Text Available Abstract Background Chronic lumbar radicular pain can be described as neuropathic pain along the distribution of a particular nerve root. The dorsal root ganglion has been implicated in its pathogenesis by giving rise to abnormal impulse generation as a result of irritation, direct compression and sensitization. Chronic lumbar radicular pain is commonly treated with medications, physiotherapy and epidural steroid injections. Epidural steroid injections are associated with several common and rarer side effects such as spinal cord infarction and death. It is essential and advantageous to look for alternate interventions which could be effective with fewer side effects. Pulse radio frequency is a relatively new technique and is less destructive then conventional radiofrequency. Safety and effectiveness of pulse radio frequency in neuropathic pain has been demonstrated in animal and humans studies. Although its effects on dorsal root ganglion have been studied in animals there is only one randomized control trial in literature demonstrating its effectiveness in cervical radicular pain and none in lumbar radicular pain. Our primary objective is to study the feasibility of a larger trial in terms of recruitment and methodology. Secondary objectives are to compare the treatment effects and side effects. Methods/designs This is a single-center, parallel, placebo-controlled, triple-blinded (patients, care-givers, and outcome assessors, randomized control trial. Participants will have a history of chronic lumbar radicular pain for at least 4 months in duration. Once randomized, all patients will have an intervention involving fluoroscopy guided needle placement to appropriate dorsal root ganglion. After test stimulation in both groups; the study group will have a pulse radio frequency treatment at 42°C for 120 s to the dorsal root ganglion, with the control group having only low intensity test stimulation for the same duration. Primary outcome is to

  4. Propofol Modulates Agonist-induced Transient Receptor Potential Vanilloid Subtype-1 Receptor Desensitization via a Protein Kinase Cε-dependent Pathway in Mouse Dorsal Root Ganglion Sensory Neurons

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    Wickley, Peter J.; Yuge, Ryo; Russell, Mary S.; Zhang, Hongyu; Sulak, Michael A.; Damron, Derek S.

    2011-01-01

    Background The activity of transient receptor potential vanilloid subtype-1 (TRPV1) receptors, key nociceptive transducers in dorsal root ganglion sensory neurons, is enhanced by protein kinase C ε (PKCε) activation. The intravenous anesthetic propofol has been shown to activate PKCε. Our objectives were to examine whether propofol modulates TRPV1 function in dorsal root ganglion neurons via activation of PKCε. Methods Lumbar dorsal root ganglion neurons from wild-type and PKCε-null mice were isolated and cultured for 24 h. Intracellular free Ca2+ concentration was measured in neurons by using fura-2 acetoxymethyl ester. The duration of pain-associated behaviors was also assessed. Phosphorylation of PKCε and TRPV1 and the cellular translocation of PKCε from cytosol to membrane compartments were assessed by immunoblot analysis. Results In wild-type neurons, repeated stimulation with capsaicin (100 nM) progressively decreased the transient rise in intracellular free Ca2+ concentration. After desensitization, exposure to propofol rescued the Ca2+ response. The resensitizing effect of propofol was absent in neurons obtained from PKCε-null mice. Moreover, the capsaicin-induced desensitization of TRPV1 was markedly attenuated in the presence of propofol in neurons from wild-type mice but not in neurons from PKCε-null mice. Propofol also prolonged the duration of agonist-induced pain associated behaviors in wild-type mice. In addition, propofol increased phosphorylation of PKCε as well as TRPV1 and stimulated translocation of PKCε from cytosolic to membrane fraction. Discussion Our results indicate that propofol modulates TRPV1 sensitivity to capsaicin and that this most likely occurs through a PKCε-mediated phosphorylation of TRPV1. PMID:20808213

  5. Regulation of the Spontaneous Augmentation of Na_V1.9 in Mouse Dorsal Root Ganglion Neurons : Effect of PKA and PKC Pathways

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    Nobukuni Ogata; Noriko Uryu; Taixing Zheng; Jun-ichi Kakimura

    2010-01-01

    Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R) isoforms of voltage-gated sodium channels, NaV1.8 and NaV1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is NaV1.9: our previous studies revealed a unique property of the NaV1.9 current, i.e., the NaV1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording (“spontaneous augmentation of NaV1.9”). However, the mechanis...

  6. Cytotoxic effect of commercially available methylprednisolone acetate with and without reduced preservatives on dorsal root ganglion sensory neurons in rats.

    Science.gov (United States)

    Knezevic, Nebojsa Nick; Candido, Kenneth D; Cokic, Ivan; Krbanjevic, Aleksandar; Berth, Sarah L; Knezevic, Ivana

    2014-01-01

    Epidural and intrathecal injections of methylprednisolone acetate (MPA) have become the most commonly performed interventional procedures in the United States and worldwide in the last 2 decades. However neuraxial MPA injection has been dogged by controversy regarding the presence of different additives used in commercially prepared glucocorticoids. We previously showed that MPA could be rendered 85% free of polyethylene glycol (PEG) by a simple physical separation of elements in the suspension. The objective of the present study was to explore a possible cytotoxic effect of commercially available MPA (with intact or reduced preservatives) on rat sensory neurons. We exposed primary dissociated rat dorsal root ganglia (DRG) sensory neurons to commercially available MPA for 24 hours with either the standard (commercial) concentration of preservatives or to different fractions following separation (MPA suspension whose preservative concentration had been reduced, or fractions containing higher concentrations of preservatives). Cells were stained with the TUNEL assay kit to detect apoptotic cells and images were taken on the Bio-Rad Laser Sharp-2000 system. We also detected expression of caspase-3, as an indicator of apoptosis in cell lysates. We exposed sensory neurons from rat DRG to different concentrations of MPA from the original commercially prepared vial. TUNEL assay showed dose-related responses and increased percentages of apoptotic cells with increasing concentrations of MPA. Increased concentrations of MPA caused 1.5 - 2 times higher caspase-3 expression in DRG sensory neurons than in control cells (ANOVA, P = 0.001). Our results showed that MPA with reduced preservatives caused significantly less apoptosis observed with TUNEL assay labeling (P neurons exposed to MPA from a commercially prepared vial or "clear phase" that contained higher concentrations of preservatives. Even though MPA with reduced preservatives caused 12.5% more apoptosis in DRG sensory

  7. Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome (CRPS) Recurrence after Amputation for CRPS, and Failure of Conventional Spinal Cord Stimulation.

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    Goebel, Andreas; Lewis, Sarah; Phillip, Rhodri; Sharma, Manohar

    2017-04-18

    Limb amputation is sometimes being performed in long-standing complex regional pain syndrome (CRPS), although little evidence is available guiding management decisions, including how CRPS recurrence should be managed. This report details the management of a young soldier with CRPS recurrence 2 years after midtibial amputation for CRPS. Conventional spinal cord stimulation did not achieve paraesthetic coverage, or pain relief in the stump, whereas L4 dorsal root ganglion stimulation achieved both coverage and initially modest pain relief, and over time, substantial pain relief. Current evidence does not support the use of amputation to improve either pain or function in CRPS. Before a decision is made, in exceptional cases, about referral for amputation, dorsal root ganglion stimulation should be considered as a potentially effective treatment, even where conventional spinal cord stimulator treatment has failed to achieve reliable paraesthetic cover. Furthermore, this treatment may provide pain relief in those patients with CRPS recurrence in the stump after amputation. © 2017 World Institute of Pain.

  8. Inhibition of [3H]resiniferatoxin binding to rat dorsal root ganglion membranes as a novel approach in evaluating compounds with capsaicin-like activity.

    Science.gov (United States)

    Szallasi, A; Szolcsanyi, J; Szallasi, Z; Blumberg, P M

    1991-11-01

    We have recently reported the specific binding of [3H]resiniferatoxin to sensory ganglion membranes; this binding appears to represent the postulated vanilloid (capsaicin) receptor. In the present report, we compare the structure/activity relations for binding to rat dorsal root ganglion membranes and for biological responses in the rat, using a series of vanilloids of the capsaicin (homovanilloyl-decylamide, homovanilloyl-dodecylamide, homovanilloyl-cyclododecylamide, homovanilloyl-hexadecylamide, homovanilloyl-piperidine and nonenoyl-homoveratrylamide) and resiniferatoxin (tinyatoxin, 12-deoxyphorbol 13-phenylacetate 20-homovanillate) classes. We find that all the tested biologically active vanilloids, but not the inactive structure analogs, compete for the [3H]resiniferatoxin binding sites in rat dorsal root ganglion membranes, and we conclude that the [3H]resiniferatoxin binding assay may provide an efficient approach for evaluating such compounds. We also provide evidence that the [3H]resiniferatoxin receptor is likely to recognize vanilloids which are inserted into the membranes; and that the apparent activity of capsaicinoids may be significantly influenced by factors other than equilibrium binding affinities.

  9. Neurite growth acceleration of adult Dorsal Root Ganglion neurons illuminated by low-level Light Emitting Diode light at 645 nm.

    Science.gov (United States)

    Burland, Marion; Paris, Lambert; Quintana, Patrice; Bec, Jean-Michel; Diouloufet, Lucie; Sar, Chamroeun; Boukhaddaoui, Hassan; Charlot, Benoit; Braga Silva, Jefferson; Chammas, Michel; Sieso, Victor; Valmier, Jean; Bardin, Fabrice

    2015-06-01

    The effect of a 645 nm Light Emitting Diode (LED) light irradiation on the neurite growth velocity of adult Dorsal Root Ganglion (DRG) neurons with peripheral axon injury 4-10 days before plating and without previous injury was investigated. The real amount of light reaching the neurons was calculated by taking into account the optical characteristics of the light source and of media in the light path. The knowledge of these parameters is essential to be able to compare results of the literature and a way to reduce inconsistencies. We found that 4 min irradiation of a mean irradiance of 11.3 mW/cm(2) (corresponding to an actual irradiance reaching the neurons of 83 mW/cm(2)) induced a 1.6-fold neurite growth acceleration on non-injured neurons and on axotomized neurons. Although the axotomized neurons were naturally already in a rapid regeneration process, an enhancement was found to occur while irradiating with the LED light, which may be promising for therapy applications. Dorsal Root Ganglion neurons (A) without previous injury and (B) subjected to a conditioning injury. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Effect of TRPV4-p38 MAPK Pathway on Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

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    Yu-Juan Qu

    2016-01-01

    Full Text Available The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4α-phorbol 12,13-didecanoate (4α-PDD, an agonist of TRPV4 and anisomycin (an agonist of p38, but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4 and SB203580 (an inhibitor of p38. The protein expressions of p38 and P-p38 were upregulated by 4α-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4α-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4α-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion.

  11. Effects of niflumic acid on γ-aminobutyric acid-induced currents in isolated dorsal root ganglion neurons of neuropathic pain rats.

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    Wang, Li-Jie; Wang, Yang; Chen, Meng-Jie; Tian, Zhen-Pu; Lu, Bi-Han; Mao, Ke-Tao; Zhang, Liang; Zhao, Lei; Shan, Li-Ya; Li, Li; Si, Jun-Qiang

    2017-08-01

    Niflumic acid (NFA) is a type of non-steroidal anti-inflammatory drug. Neuropathic pain is caused by a decrease in presynaptic inhibition mediated by γ-aminobutyric acid (GABA). In the present study, a whole-cell patch-clamp technique and intracellular recording were used to assess the effect of NFA on GABA-induced inward current in dorsal root ganglion (DRG) neurons of a chronic constriction injury (CCI) model. It was observed that 1-1,000 µmol/l GABA induced a concentration-dependent inward current in DRG neurons. Compared with pseudo-operated rats, the thermal withdrawal latency (TWL) of CCI rats significantly decreased (PNFA group (50 and 300 µmol/l) were significantly longer than that of the CCI group (PNFA (5.32±3.51, 33.8±5.20, and 52.2±6.32%, respectively; PNFA, respectively (PNFA exerted a strong inhibitory effect on the peak value of GABA-induced current, and the GABA-induced response was inhibited by the same concentrations of NFA (1, 10 and 100 µmol/l) in the control and CCI groups (PNFA reduced the primary afferent depolarization (PAD) associated with neuropathic pain and mediated by the GABAA receptor. NFA may regulate neuropathic pain by inhibiting dorsal root reflexes, which are triggered PAD.

  12. Insulin Therapy in Diabetic Hyperglycemic Emergencies

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    Diana Machado Ramírez

    2014-09-01

    Full Text Available Background: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state are two of the most serious metabolic emergencies in diabetic patients. Objective: to identify the type of metabolic complications (diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state in order to analyze the patients’ outcome considering the plasma pH levels, as well as the mode of insulin administration. Method: a cross-sectional descriptive study was conducted in 52 patients admitted to the intensive care unit of the Enrique Cabrera Hospital from 2000 to 2007. The variables analyzed included: type of diabetes mellitus, type of acute complication, mode of insulin administration, blood gas analysis and outcome. Results: diabetic ketoacidosis occurred in 57.5 % of the type 1 diabetic patients and in the 42.5 % of the type 2 diabetics. None of the type 1 diabetics developed hyperglycemic hyperosmolar nonketotic state and this complication was observed in 23.0 % of the patients with diabetes type 2. Microdosing was the mode of insulin administration that predominated in both ketoacidosis and hyperglycemic state cases. Mortality was higher in the hyperglycemic state (67 % and using microdoses in the insulin therapy. Conclusions: diabetic ketoacidosis was the major complication. Mortality from diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state was high and the mode of insulin administration was inadequate in some patients.

  13. TNF-α enhances the currents of voltage gated sodium channels in uninjured dorsal root ganglion neurons following motor nerve injury.

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    Chen, Xi; Pang, Rui-Ping; Shen, Kai-Feng; Zimmermann, Manfred; Xin, Wen-Jun; Li, Yong-Yong; Liu, Xian-Guo

    2011-02-01

    The ectopic discharges observed in uninjured dorsal root ganglion (DRG) neurons following various lesions of spinal nerves have been attributed to functional alterations of voltage-gated sodium channels (VGSCs). Such mechanisms may be important for the development of neuropathic pain. However, the pathophysiology underlying the functional modulation of VGSCs following nerve injury is largely unknown. Here, we studied this issue with use of a selective lumbar 5 ventral root transection (L5-VRT) model, in which dorsal root ganglion (DRG) neurons remain intact. We found that the L5-VRT increased the current densities of TTX-sensitive Na channels as well as currents in Nav1.8, but not Nav1.9 channels in uninjured DRG neurons. The thresholds of action potentials decreased and firing rates increased in DRG neurons following L5-VRT. As we found that levels of tumor necrosis factor-alpha (TNF-α) increased in cerebrospinal fluid (CSF) and in DRG tissue after L5-VRT, we tested whether the increased TNF-α might result in the changes in sodium channels. Indeed, recombinant rat TNF (rrTNF) enhanced the current densities of TTX-S and Nav1.8 in cultured DRG neurons dose-dependently. Furthermore, genetic deletion of TNF receptor 1 (TNFR-1) in mice attenuated the mechanical allodynia and prevented the increase in sodium currents in DRG neurons induced by L5-VRT. These data suggest that the increase in sodium currents in uninjured DRG neurons following nerve injury might be mediated by over-production of TNF-α. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Minimally invasive convection-enhanced delivery of biologics into dorsal root ganglia: validation in the pig model and prospective modeling in humans. Technical note.

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    Pleticha, Josef; Maus, Timothy P; Christner, Jodie A; Marsh, Michael P; Lee, Kendall H; Hooten, W Michael; Beutler, Andreas S

    2014-10-01

    Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convection enhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.

  15. Effects of dorsal root ganglion destruction by adriamycin in patients with postherpetic neuralgia Efeitos da destruição da raiz dorsal ganglionar pela adriamicina em pacientes com neuralgia pós-herpética

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    He Chun-jing

    2012-06-01

    Full Text Available PURPOSE: To investigate the effects of dorsal root ganglion destruction in patients with postherpetic neuralgia (PHN. METHODS: Seventy-two patients with PHN selected were randomly divided into two groups (n=36. Group A was the control group (treated by injection and group B was the group of dorsal root ganglion destruction by adriamycin. Visual analog scale scores (VAS, SAS, SF-MPQ scores. Clinical effects and therapy safety were evaluated before therapy, one week, three and six months after therapy. Forty-four patients were available for intention-to-treat analysis. RESULTS: The average pain scores on the Likert scale were significantly reduced at each point in group B. Patients in group B reported clinical effectiveness at six months as excellent response, good response, improved but unsatisfactory or unchanged 16, 12 and 8.VAS scores at each time point after the operation were lower than that before operation and in group A, there was significant difference. Patients showed significant improvement in sleep scores in group B. There was significant difference at T2 in group A than T1. There was no significant difference in group A at T3, T4 after the operation than that before operation. Between group comparison: there was significant difference between group A and group B at each time point after the operation. CONCLUSIONS: Dorsal root ganglion destruction by adriamycin under guidance of C-arm perspective, the puncture operation was accurate without any adverse reaction or serious complications, which could effectively relieve pain of patients with postherpetic neuralgia, but the long-term effects needed further study.OBJETIVO: Investigar os efeitos da destruição da raiz dorsal ganglionar em pacientes com neuralgia pós-herpética. MÉTODOS: Setenta e dois pacientes selecionados com neuralgia pós-herpética foram randomicamente distribuídos em dois grupos (n=36. Grupo A foi o grupo controle (tratado por injeção e o grupo B foi o grupo

  16. Peripheral effects of morphine and expression of μ-opioid receptors in the dorsal root ganglia during neuropathic pain: nitric oxide signaling

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    Pol Olga

    2011-04-01

    Full Text Available Abstract Background The local administration of μ-opioid receptor (MOR agonists attenuates neuropathic pain but the precise mechanism implicated in this effect is not completely elucidated. We investigated if nitric oxide synthesized by neuronal (NOS1 or inducible (NOS2 nitric oxide synthases could modulate the local antiallodynic effects of morphine through the peripheral nitric oxide-cGMP-protein kinase G (PKG-ATP-sensitive K+ (KATP channels signaling pathway activation and affect the dorsal root ganglia MOR expression during neuropathic pain. Results In wild type (WT mice, the subplantar administration of morphine dose-dependently decreased the mechanical and thermal allodynia induced by the chronic constriction of the sciatic nerve (CCI, which effects were significantly diminished after their co-administration with different subanalgesic doses of a selective NOS1 (N-[(4S-4-amino-5-[(2-aminoethylamino]pentyl]-N'-nitroguanidine tris(trifluoroacetate salt; NANT, NOS2 (L-N(6-(1-iminoethyl-lysine; L-NIL, L-guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; ODQ, PKG ((Rp-8-(para-chlorophenylthioguanosine-3',5'-cyclic monophosphorothioate; Rp-8-pCPT-cGMPs inhibitor or a KATP channel blocker (glibenclamide. The evaluation of the expression of MOR in the dorsal root ganglia from sham-operated and sciatic nerve-injured WT, NOS1 knockout (KO and NOS2-KO mice at 21 days after surgery demonstrated that, although the basal mRNA and protein levels of MOR were similar between WT and both NOS-KO animals, nerve injury only decreased their expression in WT mice. Conclusions These results suggest that the peripheral nitric oxide-cGMP-PKG-KATP signaling pathway activation participates in the local antiallodynic effects of morphine after sciatic nerve injury and that nitric oxide, synthesized by NOS1 and NOS2, is implicated in the dorsal root ganglia down-regulation of MOR during neuropathic pain.

  17. Enhanced excitability of primary sensory neurons and altered gene expression of neuronal ion channels in dorsal root ganglion in paclitaxel-induced peripheral neuropathy.

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    Zhang, Haijun; Dougherty, Patrick M

    2014-06-01

    The mechanism of chemotherapy-induced peripheral neuropathy after paclitaxel treatment is not well understood. Given the poor penetration of paclitaxel into central nervous system, peripheral nervous system is most at risk. Intrinsic membrane properties of dorsal root ganglion neurons were studied by intracellular recordings. Multiple-gene real-time polymerase chain reaction array was used to investigate gene expression of dorsal root ganglion neuronal ion channels. Paclitaxel increased the incidence of spontaneous activity from 4.8 to 27.1% in large-sized and from 0 to 33.3% in medium-sized neurons. Paclitaxel decreased the rheobase (nA) from 1.6 ± 0.1 to 0.8 ± 0.1 in large-sized, from 1.5 ± 0.2 to 0.6 ± 0.1 in medium-sized, and from 1.6 ± 0.2 to 1.0 ± 0.1 in small-sized neurons. After paclitaxel treatment, other characteristics of membrane properties in each group remained the same except that Aδ neurons showed shorter action potential fall time (ms) (1.0 ± 0.2, n = 10 vs. 1.8 ± 0.3, n = 9, paclitaxel vs. vehicle). Meanwhile, real-time polymerase chain reaction array revealed an alteration in expression of some neuronal ion channel genes including up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 1 (fold change 1.76 ± 0.06) and Nav1.7 (1.26 ± 0.02) and down-regulation of Kir channels (Kir1.1, 0.73 ± 0.05, Kir3.4, 0.66 ± 0.06) in paclitaxel-treated animals. The increased neuronal excitability and the changes in gene expression of some neuronal ion channels in dorsal root ganglion may provide insight into the molecular and cellular basis of paclitaxel-induced neuropathy, which may lead to novel therapeutic strategies.

  18. G protein-gated inwardly rectifying potassium channel subunits 1 and 2 are down-regulated in rat dorsal root ganglion neurons and spinal cord after peripheral axotomy.

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    Lyu, Chuang; Mulder, Jan; Barde, Swapnali; Sahlholm, Kristoffer; Zeberg, Hugo; Nilsson, Johanna; Århem, Peter; Hökfelt, Tomas; Fried, Kaj; Shi, Tie-Jun Sten

    2015-07-22

    Increased nociceptive neuronal excitability underlies chronic pain conditions. Various ion channels, including sodium, calcium and potassium channels have pivotal roles in the control of neuronal excitability. The members of the family of G protein-gated inwardly rectifying potassium (GIRK) channels, GIRK1-4, have been implicated in modulating excitability. Here, we investigated the expression and distribution of GIRK1 and GIRK2 in normal and injured dorsal root ganglia (DRGs) and spinal cord of rats. We found that ~70% of the DRG neurons expressed GIRK1, while only <10% expressed GIRK2. The neurochemical profiles of GIRK1- and GIRK2-immunoreactive neurons were characterized using the neuronal markers calcitonin gene-related peptide, isolectin-B4 and neurofilament-200, and the calcium-binding proteins calbindin D28k, calretinin, parvalbumin and secretagogin. Both GIRK subunits were expressed in DRG neurons with nociceptive characteristics. However, while GIRK1 was widely expressed in several sensory neuronal subtypes, GIRK2 was detected mainly in a group of small C-fiber neurons. In the spinal dorsal horn, GIRK1- and -2-positive cell bodies and processes were mainly observed in lamina II, but also in superficial and deeper layers. Abundant GIRK1-, but not GIRK2-like immunoreactivity, was found in the ventral horn (laminae VI-X). Fourteen days after axotomy, GIRK1 and GIRK2 were down-regulated in DRG neurons at the mRNA and protein levels. Both after axotomy and rhizotomy there was a reduction of GIRK1- and -2-positive processes in the dorsal horn, suggesting a presynaptic localization of these potassium channels. Furthermore, nerve ligation caused accumulation of both subunits on both sides of the lesion, providing evidence for anterograde and retrograde fast axonal transport. Our data support the hypothesis that reduced GIRK function is associated with increased neuronal excitability and causes sensory disturbances in post-injury conditions, including neuropathic

  19. Spinorphin inhibits membrane depolarization- and capsaicin-induced intracellular calcium signals in rat primary nociceptive dorsal root ganglion neurons in culture.

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    Ayar, Ahmet; Ozcan, Mete; Kuzgun, Kemal Tuğrul; Kalkan, Omer Faruk

    2015-01-01

    Spinorphin is a potential endogenous antinociceptive agent although the mechanism(s) of its analgesic effect remain unknown. We conducted this study to investigate, by considering intracellular calcium concentrations as a key signal for nociceptive transmission, the effects of spinorphin on cytoplasmic Ca(2+) ([Ca(2+)]i) transients, evoked by high-K(+) (30 mM) depolariasation or capsaicin, and to determine whether there were any differences in the effects of spinorphin among subpopulation of cultured rat dorsal root ganglion (DRG) neurons. DRG neurons were cultured on glass coverslips following enzymatic digestion and mechanical agitation, and loaded with the calcium sensitive dye fura-2 AM (1 µM). Intracellular calcium responses in individual DRG neurons were quantified using standard fura-2 based ratiometric calcium imaging technique. All data were analyzed by using unpaired t test, p nociceptive subtypes of this primary sensory neurons suggesting that peripheral site is involved in the pain modulating effect of this endogenous agent.

  20. Effects of dragon's blood resin and its component loureirin B on tetrodotoxin-sensitive voltage-gated sodium currents in rat dorsal root ganglion neurons.

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    Xiangming, Liu; Su, Chen; Shijin, Yin; Zhinan, Mei

    2004-08-01

    Using whole-cell patch clamp technique on the membrane of freshly isolated dorsal root ganglion (DRG) neurons, the effects of dragon's blood resin and its important component loureirin B on tetrodotoxin-sensitive (TTX-S) voltage-gated sodium currents were observed. The results show that both blood resin and loureirin B could suppress TTX-S voltage-gated sodium currents in a dose-dependent way. The peak current amplitudes and the steady-state activation and inactivation curves are also made to shift by 0.05% blood resin and 0.2 mmol/L loureirin B. These results demonstrate that the effects of blood resin on TTX-S sodium current may contribute to loureirin B in blood resin. Perhaps the analgesic effect of blood resin is caused partly by loureirin B directly interfering with the nociceptive transmission of primary sensory neurons.

  1. Muscle injury in rats induces upregulation of inflammatory cytokines in injured muscle and calcitonin gene-related peptide in dorsal root ganglia innervating the injured muscle.

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    Sakuma, Yoshihiro; Miyagi, Masayuki; Inoue, Gen; Ishikawa, Tetsuhiro; Kamoda, Hiroto; Yamauchi, Kazuyo; Orita, Sumihisa; Suzuki, Miyako; Oikawa, Yasuhiro; Inage, Kazuhide; Kubota, Go; Sainoh, Takeshi; Sato, Jun; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-10-01

    In this study we evaluated the relationships among the behavioral changes after muscle injury, histological changes, changes in inflammatory cytokines in the injured muscle, and changes in the sensory nervous system innervating the muscle in rats. We established a model of muscle injury in rats using a dropped weight. Behavior was assessed using the CatWalk system. Subsequently, bilateral gastrocnemius muscles and dorsal root ganglia (DRGs) were resected. Muscles were stained with hematoxylin and eosin, and inflammatory cytokines in injured muscles were assayed. DRGs were immunostained for calcitonin gene-related peptide (CGRP). Changes of behavior and upregulation of inflammatory cytokines in injured muscles subsided within 2 days of injury. Repaired tissue was observed 3 weeks after injury. However, upregulation of CGRP in DRG neurons continued for 2 weeks after injury. These findings may explain in part the pathological mechanism of persistent muscle pain. Muscle Nerve 54: 776-782, 2016. © 2016 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

  2. Selective Small Molecule Activators of TREK-2 Channels Stimulate Dorsal Root Ganglion c-Fiber Nociceptor Two-Pore-Domain Potassium Channel Currents and Limit Calcium Influx.

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    Dadi, Prasanna K; Vierra, Nicholas C; Days, Emily; Dickerson, Matthew T; Vinson, Paige N; Weaver, C David; Jacobson, David A

    2017-03-15

    The two-pore-domain potassium (K2P) channel TREK-2 serves to modulate plasma membrane potential in dorsal root ganglia c-fiber nociceptors, which tunes electrical excitability and nociception. Thus, TREK-2 channels are considered a potential therapeutic target for treating pain; however, there are currently no selective pharmacological tools for TREK-2 channels. Here we report the identification of the first TREK-2 selective activators using a high-throughput fluorescence-based thallium (Tl+) flux screen (HTS). An initial pilot screen with a bioactive lipid library identified 11-deoxy prostaglandin F2α as a potent activator of TREK-2 channels (EC50 ≈ 0.294 μM), which was utilized to optimize the TREK-2 Tl+ flux assay (Z' = 0.752). A HTS was then performed with 76 575 structurally diverse small molecules. Many small molecules that selectively activate TREK-2 were discovered. As these molecules were able to activate single TREK-2 channels in excised membrane patches, they are likely direct TREK-2 activators. Furthermore, TREK-2 activators reduced primary dorsal root ganglion (DRG) c-fiber Ca2+ influx. Interestingly, some of the selective TREK-2 activators such as 11-deoxy prostaglandin F2α were found to inhibit the K2P channel TREK-1. Utilizing chimeric channels containing portions of TREK-1 and TREK-2, the region of the TREK channels that allows for either small molecule activation or inhibition was identified. This region lies within the second pore domain containing extracellular loop and is predicted to play an important role in modulating TREK channel activity. Moreover, the selective TREK-2 activators identified in this HTS provide important tools for assessing human TREK-2 channel function and investigating their therapeutic potential for treating chronic pain.

  3. Autologous nucleus pulposus transplantation to lumbar 5 dorsal root ganglion after epineurium dissection in rats: a modified model of non-compressive lumbar herniated intervertebral disc.

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    Zhang, Jin-jun; Song, Wu; Luo, Wen-ying; Wei, Ming; Sun, Lai-bao; Zou, Xue-nong; Liao, Wei-ming

    2011-07-05

    Nucleus pulposus of intervertebral discs has proinflammatory characteristics that play a key role in neuropathic pain in lumbar herniated intervertebral disc. One of the most commonly used animal models (the traditional model) of non-compressive lumbar herniated intervertebral disc is created by L4-L5 hemilaminectomy and the application of autologous nucleus pulposus to cover the left L4 and L5 nerve roots in rats. However, such procedures have the disadvantages of excessive trauma and low success rate. We proposed a modified model of non-compressive lumbar herniated intervertebral disc in which only the left L5 dorsal root ganglion is exposed and transplanted with autologous nucleus pulposus following incision of epineurium. We aimed to compare the modified model with the traditional one with regard to trauma and success rate. Thirty Sprague-Dawley male rats were randomized into three groups: sham operation group (n = 6), traditional group (n = 12), and modified group (n = 12). The amount of blood loss and operative time for each group were analyzed. The paw withdrawal threshold of the left hind limb to mechanical stimuli and paw withdrawal latency to heat stimuli were examined from the day before surgery to day 35 after surgery. Compared with the traditional group, the modified group had shorter operative time, smaller amount of blood loss, and higher success rate (91.7% versus 58.3%, P lumbar herniated intervertebral disc with less trauma and more stable pain ethology.

  4. Efficacy and factors determining the outcome of dorsal root entry zone lesioning procedure (DREZotomy) in the treatment of intractable pain syndrome.

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    Piyawattanametha, Nontaphon; Sitthinamsuwan, Bunpot; Euasobhon, Pramote; Zinboonyahgoon, Nantthasorn; Rushatamukayanunt, Pranee; Nunta-Aree, Sarun

    2017-10-09

    Chronic pain is a disabling condition that adversely affects patient quality of life. The dorsal root entry zone lesioning procedure (DREZotomy) is a modality used to treat intractable pain caused by insults to neural structures. This study aimed to investigate the efficacy of and the factors that determine the outcome of microsurgical DREZotomy (MDT). All consecutive patients who underwent MDT for treatment of intractable pain during September 2008 to December 2016 were enrolled. Demographic data, clinical characteristics, intraoperative findings, and postoperative outcomes were analyzed. The 40 included patients underwent MDT for relief of intractable pain caused by 27 brachial plexus injuries (BPIs), 6 spinal cord injuries, 3 neoplasms, and 4 other causes. A significant reduction in pain was observed post-MDT for both average (p dermatomes (OR, 1.30; 95% CI, 1.01-1.67; p = 0.039) were significantly associated with good maximal pain relief. MDT is an effective procedure for treatment of intractable pain in well-selected patients, particularly in cases with brachial plexus avulsion pain. Injury of the spinal nerve root (brachial plexus avulsion and cauda equina injury) was associated with good average pain relief and pain freedom, and electrical pain and lower number of painful dermatomes were associated with good maximal pain relief. The results are useful in the selection of candidates for DREZotomy and prediction of surgical outcome.

  5. Upregulation of adrenomedullin in the spinal cord and dorsal root ganglia in the early phase of CFA-induced inflammation in rats.

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    Hong, Yanguo; Liu, Yushan; Chabot, Jean-Guy; Fournier, Alain; Quirion, Rémi

    2009-11-01

    Adrenomedullin (AM), a member of calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pronociceptive mediator [28]. This study was undertaken to investigate the role of AM in a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Injection of CFA, but not of saline, in the unilateral hindpaw produced an increase in the expression of AM-like immunoreactivity (AM-IR) in laminae I-II of the spinal cord as well as in small- and medium-sized dorsal root ganglion (DRG) neurons at 48 h. The content of AM in DRG on the side ipsilateral to CFA injection started to increase at 4 h and remained at high levels at 24 and 48 h. The selective antagonist of AM receptors, AM(22-52), administered intrathecally (i.t.) 24 h after CFA injection inhibited inflammation-associated hyperalgesia in a dose-dependent manner (2, 5 and 10 nmol). Impressively, this anti-hyperalgesic effect lasted for at least 24 h. I.t. administration of AM(22-52) (10 nmol) also reversed CFA-induced increase in AM-IR in the spinal dorsal horn and DRG. Furthermore, blockade of AM receptors abolished CFA-induced changes in the expression and content of CGRP-like immunoreactivity in these regions. Taken together, our results suggest that the upregulation of AM in DRG neurons contributes to the development of inflammatory pain, and this effect is mediated, at least in part, by enhancing the expression and release of CGRP. Blocking AM receptor downstream signaling effects using antagonists has the potential of relieving pain following the induction of inflammation.

  6. Bromodomain-containing Protein 4 Activates Voltage-gated Sodium Channel 1.7 Transcription in Dorsal Root Ganglia Neurons to Mediate Thermal Hyperalgesia in Rats.

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    Hsieh, Ming-Chun; Ho, Yu-Cheng; Lai, Cheng-Yuan; Wang, Hsueh-Hsiao; Lee, An-Sheng; Cheng, Jen-Kun; Chau, Yat-Pang; Peng, Hsien-Yu

    2017-11-01

    Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1.7, which is a key pain-related ion channel. The intraplantar complete Freund's adjuvant injections resulted in thermal hyperalgesia (4.0 ± 1.5 s; n = 7). The immunohistochemistry and immunoblotting results demonstrated an increase in the bromodomain-containing protein 4-expressing dorsal root ganglia neurons (3.78 ± 0.38 fold; n = 7) and bromodomain-containing protein 4 protein levels (2.62 ± 0.39 fold; n = 6). After the complete Freund's adjuvant injection, histone H3 protein acetylation was enhanced in the voltage-gated sodium channel 1.7 promoter, and cyclin-dependent kinase 9 and phosphorylation of RNA polymerase II were recruited to this area. Furthermore, the voltage-gated sodium channel 1.7-mediated currents were enhanced in neurons of the complete Freund's adjuvant rats (55 ± 11 vs. 19 ± 9 pA/pF; n = 4 to 6 neurons). Using bromodomain-containing protein 4-targeted antisense small interfering RNA to the complete Freund's adjuvant-treated rats, the authors demonstrated a reduction in the expression of bromodomain-containing protein 4 (0.68 ± 0.16 fold; n = 7), a reduction in thermal hyperalgesia (7.5 ± 1.5 s; n = 7), and a reduction in the increased voltage-gated sodium channel 1.7 currents (21 ± 4 pA/pF; n = 4 to 6 neurons). Complete Freund's adjuvant triggers enhanced bromodomain-containing protein 4 expression, ultimately leading to the enhanced excitability of nociceptive neurons and thermal hyperalgesia. This effect is

  7. Effects of serum immunoglobulins from patients with complex regional pain syndrome (CRPS) on depolarisation-induced calcium transients in isolated dorsal root ganglion (DRG) neurons.

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    Reilly, Joanne M; Dharmalingam, Backialakshmi; Marsh, Stephen J; Thompson, Victoria; Goebel, Andreas; Brown, David A

    2016-03-01

    Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. Depolarisation-induced [Ca(2+)]i transients were generated by applying 30 mM KCl for 2 min and monitored by Fura-2 fluorescence imaging. No IgGs tested (including 3 from CRPS patients) had any significant effect on these [Ca(2+)]i transients. However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1 μM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested. Copyright © 2015. Published by Elsevier Inc.

  8. Adeno-associated virus and lentivirus vectors mediate efficient and sustained transduction of cultured mouse and human dorsal root ganglia sensory neurons.

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    Fleming, J; Ginn, S L; Weinberger, R P; Trahair, T N; Smythe, J A; Alexander, I E

    2001-01-01

    Peripheral nervous system (PNS) sensory neurons are directly involved in the pathophysiology of numerous inherited and acquired neurological conditions. Therefore, efficient and stable gene delivery to these postmitotic cells has significant therapeutic potential. Among contemporary vector systems capable of neuronal transduction, only those based on herpes simplex virus have been extensively evaluated in PNS neurons. We therefore investigated the transduction performance of recombinant adeno-associated virus type 2 (AAV) and VSV-G-pseudotyped lentivirus vectors derived from human immunodeficiency virus (HIV-1) in newborn mouse and fetal human dorsal root ganglia (DRG) sensory neurons. In dissociated mouse DRG cultures both vectors achieved efficient transduction of sensory neurons at low multiplicities of infection (MOIs) and sustained transgene expression within a 28-day culture period. Interestingly, the lentivirus vector selectively transduced neurons in murine cultures, in contrast to human cultures, in which Schwann and fibroblast-like cells were also transduced. Recombinant AAV transduced all three cell types in both mouse and human cultures. After direct microinjection of murine DRG explants, maximal transduction efficiencies of 20 and 200 transducing units per neuronal transductant were achieved with AAV and lentivirus vectors, respectively. Most importantly, both vectors achieved efficient and sustained transduction of human sensory neurons in dissociated cultures, thereby directly demonstrating the exciting potential of these vectors for gene therapy applications in the PNS.

  9. Toll-like receptor 2 contributes to chemokine gene expression and macrophage infiltration in the dorsal root ganglia after peripheral nerve injury

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    Lee Sung Joong

    2011-09-01

    Full Text Available Abstract Background We have previously reported that nerve injury-induced neuropathic pain is attenuated in toll-like receptor 2 (TLR2 knock-out mice. In these mice, inflammatory gene expression and spinal cord microglia actvation is compromised, whereas the effects in the dorsal root ganglia (DRG have not been tested. In this study, we investigated the role of TLR2 in inflammatory responses in the DRG after peripheral nerve injury. Results L5 spinal nerve transection injury induced the expression of macrophage-attracting chemokines such as CCL2/MCP-1 and CCL3/MIP-1 and subsequent macrophage infiltration in the DRG of wild-type mice. In TLR2 knock-out mice, however, the induction of chemokine expression and macrophage infiltration following nerve injury were markedly reduced. Similarly, the induction of IL-1β and TNF-α expression in the DRG by spinal nerve injury was ameliorated in TLR2 knock-out mice. The reduced inflammatory response in the DRG was accompanied by attenuation of nerve injury-induced spontaneous pain hypersensitivity in TLR2 knock-out mice. Conclusions Our data show that TLR2 contributes to nerve injury-induced proinflammatory chemokine/cytokine gene expression and macrophage infiltration in the DRG, which may have relevance in the reduced pain hypersensitivity in TLR2 knock-out mice after spinal nerve injury.

  10. The Venom of the Spider Selenocosmia Jiafu Contains Various Neurotoxins Acting on Voltage-Gated Ion Channels in Rat Dorsal Root Ganglion Neurons

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    Zhaotun Hu

    2014-03-01

    Full Text Available Selenocosmia jiafu is a medium-sized theraphosid spider and an attractive source of venom, because it can be bred in captivity and it produces large amounts of venom. We performed reversed-phase high-performance liquid chromatography (RP-HPLC and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS analyses and showed that S. jiafu venom contains hundreds of peptides with a predominant mass of 3000–4500 Da. Patch clamp analyses indicated that the venom could inhibit voltage-gated Na+, K+ and Ca2+ channels in rat dorsal root ganglion (DRG neurons. The venom exhibited inhibitory effects on tetrodotoxin-resistant (TTX-R Na+ currents and T-type Ca2+ currents, suggesting the presence of antagonists to both channel types and providing a valuable tool for the investigation of these channels and for drug development. Intra-abdominal injection of the venom had severe toxic effects on cockroaches and caused death at higher concentrations. The LD50 was 84.24 μg/g of body weight in the cockroach. However, no visible symptoms or behavioral changes were detected after intraperitoneal injection of the venom into mice even at doses up to 10 mg/kg body weight. Our results provide a basis for further case-by-case investigations of peptide toxins from this venom.

  11. The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant

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    Han Ji-Sheng

    2008-12-01

    Full Text Available Abstract Background The 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 until day 28 following injection. Results Thermal hyperalgesia was evident from day 1 to day 28 with peak at day 7, while mechanical allodynia persisted from day 1 to day 14 and was greatest at day 7. Intrathecal administration of AMG 9810 at day 7, a selective TRPV1 antagonist, significantly reduced thermal hyperalgesia and mechanical allodynia. TRPV1 expression in DRG detected by Western blotting was increased relative to baseline throughout the observation period. Double labeling of TRPV1 with neuronal marker neurofilament 200 (NF200, calcitonin gene-related peptide (CGRP or isolectin B4 (IB4 was used to distinguish different subtypes of DRG neurons. TRPV1 expression was increased in the medium-sized myelinated A fiber (NF200 positive neurons and in small non-peptidergic (IB4 positive neurons from day 1 to day 14 and was increased in small peptidergic (CGRP positive neurons from day 1 to day 28. Conclusion TRPV1 expression increases in all three types of DRG neurons after CFA injection and plays a role in CFA-induced chronic inflammatory pain including thermal hyperalgesia and mechanical allodynia.

  12. Effects of (−-Gallocatechin-3-Gallate on Tetrodotoxin-Resistant Voltage-Gated Sodium Channels in Rat Dorsal Root Ganglion Neurons

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    Jian-Min Jiang

    2013-05-01

    Full Text Available The (−-gallocatechin-3-gallate (GCG concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant compared to other isoforms and functionally linked to nociception. In this study, the effects of GCG on tetrodotoxin-resistant Na+ currents were investigated in rat primary cultures of dorsal root ganglion neurons via the whole-cell patch-clamp technique. We found that 1 μM GCG reduced the amplitudes of peak current density of tetrodotoxin-resistant Na+ currents significantly. Furthermore, the inhibition was accompanied by a depolarizing shift of the activation voltage and a hyperpolarizing shift of steady-state inactivation voltage. The percentage block of GCG (1 μM on tetrodotoxin-resistant Na+ current was 45.1% ± 1.1% in 10 min. In addition, GCG did not produce frequency-dependent block of tetrodotoxin-resistant Na+ currents at stimulation frequencies of 1 Hz, 2 Hz and 5 Hz. On the basis of these findings, we propose that GCG may be a potential analgesic agent.

  13. Increase of sodium channels (nav 1.8 and nav 1.9) in rat dorsal root ganglion neurons exposed to autologous nucleus pulposus.

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    Watanabe, Kazuyuki; Larsson, Karin; Rydevik, Björn; Konno, Shin-Ichi; Nordborg, Claes; Olmarker, Kjell

    2014-01-01

    It has been assumed that nucleus pulposus-induced activation of the dorsal root ganglion (DRG) may be related to an activation of sodium channels in the DRG neurons. In this study we assessed the expression of Nav 1.8 and Nav 1.9 following disc puncture. Thirty female Sprague-Dawley rats were used. The L4/L5 disc was punctured by a needle (n=12) and compared to a sham group without disc puncture (n=12) and a naive group (n=6). At day 1 and 7, sections of the left L4 DRG were immunostained with anti-Nav 1.8 and Nav 1.9 antibodies. At day 1 after surgery, both Nav 1.8-IR neurons and Nav 1.9-IR neurons were significantly increased in the disc puncture group compared to the sham and naive groups (p<0.05), but not at day 7. The findings in the present study demonstrate a neuronal mechanism that may be of importance in the pathophysiology of sciatic pain in disc herniation.

  14. Efficient Gene Suppression in Dorsal Root Ganglia and Spinal Cord Using Adeno-Associated Virus Vectors Encoding Short-Hairpin RNA.

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    Enomoto, Mitsuhiro; Hirai, Takashi; Kaburagi, Hidetoshi; Yokota, Takanori

    2016-01-01

    RNA interference is a powerful tool used to induce loss-of-function phenotypes through post-transcriptional gene silencing. Small interfering RNA (siRNA) molecules have been used to target the central nervous system (CNS) and are expected to have clinical utility against refractory neurodegenerative diseases. However, siRNA is characterized by low transduction efficiency, insufficient inhibition of gene expression, and short duration of therapeutic effects, and is thus not ideal for treatment of neural tissues and diseases. To address these problems, viral delivery of short-hairpin RNA (shRNA) expression cassettes that support more efficient and long-lasting transduction into target tissues is expected to be a promising delivery tool. Various types of gene therapy vectors have been developed, such as adenovirus, adeno-associated virus (AAV), herpes simplex virus and lentivirus; however, AAV is particularly advantageous because of its relative lack of immunogenicity and lack of chromosomal integration. In human clinical trials, recombinant AAV vectors are relatively safe and well-tolerated. In particular, serotype 9 of AAV (AAV9) vectors show the highest tropism for neural tissue and can cross the blood-brain barrier, and we have shown that intrathecal delivery of AAV9 yields relatively high gene transduction into dorsal root ganglia or spinal cord. This chapter describes how to successfully use AAV vectors encoding shRNA in vivo, particularly for RNA interference in the central and peripheral nervous system.

  15. [A computer simulation research for the effects of dragon's blood and its component loureirin B on sodium channel in dorsal root ganglion cells].

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    Chen, Su; Liu, Xiangming

    2006-12-01

    Using patch clamp technique the effects of dragon's blood and its component loureirin B on tetrodotoxin-sensitive sodium channel currents in dorsal root ganglion cells were observed. The experimental data were simulated with Hodgkin-Huxley model and the corresponding parameters were estimated. In addition, computer-simulated neuron action potentials in the absence and presence of drugs were produced using Hodgkin-Huxley model. The results show that the conductance of tetrodotoxin-sensitive sodium channel was fitted with m3h model well, the half-activated potentials of the sodium channel in the presence of drugs were shifted to the depolarizing direction and the threshold intensity of the cells in the presence of drugs was increased. These results demonstrate that dragon's blood and loureirin B did not resemble the tetrodotoxin which inhibited tetrodotoxin-sensitive sodium channel currents completely. Perhaps the analgesic effects of dragon's blood were partly caused by loureirin B affecting the activation, blocking the action potential generation and interfering with the transmission of painful signals into the central nervous system.

  16. Neuro-fuzzy decoding of sensory information from ensembles of simultaneously recorded dorsal root ganglion neurons for functional electrical stimulation applications

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    Rigosa, J.; Weber, D. J.; Prochazka, A.; Stein, R. B.; Micera, S.

    2011-08-01

    Functional electrical stimulation (FES) is used to improve motor function after injury to the central nervous system. Some FES systems use artificial sensors to switch between finite control states. To optimize FES control of the complex behavior of the musculo-skeletal system in activities of daily life, it is highly desirable to implement feedback control. In theory, sensory neural signals could provide the required control signals. Recent studies have demonstrated the feasibility of deriving limb-state estimates from the firing rates of primary afferent neurons recorded in dorsal root ganglia (DRG). These studies used multiple linear regression (MLR) methods to generate estimates of limb position and velocity based on a weighted sum of firing rates in an ensemble of simultaneously recorded DRG neurons. The aim of this study was to test whether the use of a neuro-fuzzy (NF) algorithm (the generalized dynamic fuzzy neural networks (GD-FNN)) could improve the performance, robustness and ability to generalize from training to test sets compared to the MLR technique. NF and MLR decoding methods were applied to ensemble DRG recordings obtained during passive and active limb movements in anesthetized and freely moving cats. The GD-FNN model provided more accurate estimates of limb state and generalized better to novel movement patterns. Future efforts will focus on implementing these neural recording and decoding methods in real time to provide closed-loop control of FES using the information extracted from sensory neurons.

  17. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity.

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    Wright, K T; Seabright, R; Logan, A; Lilly, A J; Khanim, F; Bunce, C M; Johnson, W E B

    2010-07-16

    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 extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Gene Therapy for Neuropathic Pain by Silencing of TNF-α Expression with Lentiviral Vectors Targeting the Dorsal Root Ganglion in Mice

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    Ogawa, Nobuhiro; Kawai, Hiromichi; Terashima, Tomoya; Kojima, Hideto; Oka, Kazuhiro; Chan, Lawrence; Maegawa, Hiroshi

    2014-01-01

    Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG) using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4) in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT) mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY), injury markers, and interleukin (IL)-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain. PMID:24642694

  19. Uso terapêutico da radiofrequência pulsátil no gânglio dorsal da raiz de L2 na lombalgia discogênica Uso terapéutico de la radiofrecuencia pulsátil en el ganglio dorsal de la raíz de L2 en la lumbalgia discogénica Pulsed radiofrequency on L2 dorsal root ganglion as a therapeutic method for lumbar discogenic pain

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    Fabrício Dias Assis

    2009-06-01

    Full Text Available OBJETIVO: Avaliar a eficácia da radiofrequência pulsátil sobre o gânglio da raiz dorsal de L2 no tratamento dos pacientes com lombalgia discogênica. MÉTODOS: Realizou-se análise retrospectiva de 50 pacientes portadores de lombalgia crônica discogênica atendidos no período de janeiro de 2004 a julho de 2007. O processo diagnóstico foi constituído por exame físico, ressonância magnética e bloqueio diagnóstico do gânglio da raiz dorsal de L2. Todos os pacientes foram submetidos à radiofrequência pulsátil no gânglio da raiz dorsal de L2 e acompanhados por, no mínimo, 12 meses. A intensidade de dor foi medida pela escala visual analógica (EVA de dor. RESULTADOS: A análise estatística mostrou melhora significativa da intensidade de dor (pOBJETIVO: evaluar la eficacia de la radiofrecuencia pulsátil sobre el ganglio de la raíz dorsal de L2 en el tratamiento de los pacientes con lumbalgia discogénica. MÉTODOS: fue realizado un análisis retrospectivo de 50 pacientes portadores de lumbalgia crónica discogénica, atendidos en el periodo de Enero de 2004 a Julio de 2007. El proceso diagnóstico constó de un examen físico, resonancia magnética y bloqueo diagnóstico del ganglio de la raíz dorsal de L2. Todos los pacientes fueron sometidos a la radiofrecuencia pulsátil en el ganglio de la raíz dorsal de L2 y seguidos por 12 meses, como mínimo. La intensidad del dolor fue medida por la escala visual analógica del dolor. RESULTADOS: el análisis estadístico mostró mejoría significativa de la intensidad del dolor (pOBJECTIVE: to evaluate the effectiveness of pulsate radio-frequency on L2 dorsal root ganglion for chronic discogenic low back pain. Of L2 in the treatment of the patient with discogenic low back pain. METHODS: Between January 2004 and July 2007, 50 patients with diagnosis of low back discogenic pain were retrospectively assessed based on physical examination, magnetic resonance imaging findings and selective L

  20. Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

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    Berta Temugin

    2012-03-01

    Full Text Available Abstract Background Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β. Matrix metalloprotease-9 (MMP-9 has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs and up-regulation of IL-1β in dorsal root ganglia (DRGs, and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results Subcutaneous morphine injection (10 mg/kg induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.

  1. Regulation of the spontaneous augmentation of Na(V)1.9 in mouse dorsal root ganglion neurons: effect of PKA and PKC pathways.

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    Kakimura, Jun-ichi; Zheng, Taixing; Uryu, Noriko; Ogata, Nobukuni

    2010-03-19

    Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R) isoforms of voltage-gated sodium channels, Na(V)1.8 and Na(V)1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is Na(V)1.9: our previous studies revealed a unique property of the Na(V)1.9 current, i.e., the Na(V)1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording ("spontaneous augmentation of Na(V)1.9"). However, the mechanism underlying the spontaneous augmentation of Na(V)1.9 is still unclear. In this study, we examined the effects of protein kinases A and C (PKA and PKC), on the spontaneous augmentation of Na(V)1.9. The spontaneous augmentation of the Na(V)1.9 current was significantly suppressed by activation of PKA, whereas activation of PKA did not affect the voltage dependence of inactivation for the Na(V)1.9 current. On the contrary, the finding that activation of PKC can affect the voltage dependence of inactivation for Na(V)1.9 in the perforated patch recordings, where the augmentation does not occur, suggests that the effects of PMA are independent of the augmentation process. These results indicate that the spontaneous augmentation of Na(V)1.9 was regulated directly by PKA, and indirectly by PKC.

  2. Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons.

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    Fukuoka, Tetsuo; Kobayashi, Kimiko; Yamanaka, Hiroki; Obata, Koichi; Dai, Yi; Noguchi, Koichi

    2008-09-10

    We compared the distribution of the alpha-subunit mRNAs of voltage-gated sodium channels Nav1.1-1.3 and Nav1.6-1.9 and a related channel, Nax, in histochemically identified neuronal subpopulations of the rat dorsal root ganglia (DRG). In the naïve DRG, the expression of Nav1.1 and Nav1.6 was restricted to A-fiber neurons, and they were preferentially expressed by TrkC neurons, suggesting that proprioceptive neurons possess these channels. Nav1.7, -1.8, and -1.9 mRNAs were more abundant in C-fiber neurons compared with A-fiber ones. Nax was evenly expressed in both populations. Although Nav1.8 and -1.9 were preferentially expressed by TrkA neurons, other alpha-subunits were expressed independently of TrkA expression. Actually, all IB4(+) neurons expressed both Nav1.8 and -1.9, and relatively limited subpopulations of IB4(+) neurons (3% and 12%, respectively) expressed Nav1.1 and/or Nav1.6. These findings provide useful information in interpreting the electrophysiological characteristics of some neuronal subpopulations of naïve DRG. After L5 spinal nerve ligation, Nav1.3 mRNA was up-regulated mainly in A-fiber neurons in the ipsilateral L5 DRG. Although previous studies demonstrated that nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF) reversed this up-regulation, the Nav1.3 induction was independent of either TrkA or GFRalpha1 expression, suggesting that the induction of Nav1.3 may be one of the common responses of axotomized DRG neurons without a direct relationship to NGF/GDNF supply. (c) 2008 Wiley-Liss, Inc.

  3. Glycosylation alters steady-state inactivation of sodium channel Nav1.9/NaN in dorsal root ganglion neurons and is developmentally regulated.

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    Tyrrell, L; Renganathan, M; Dib-Hajj, S D; Waxman, S G

    2001-12-15

    Na channel NaN (Na(v)1.9) produces a persistent TTX-resistant (TTX-R) current in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia. Na(v)1.9-specific antibodies react in immunoblot assays with a 210 kDa protein from the membrane fractions of adult DRG and trigeminal ganglia. The size of the immunoreactive protein is in close agreement with the predicted Na(v)1.9 theoretical molecular weight of 201 kDa, suggesting limited glycosylation of this channel in adult tissues. Neonatal rat DRG membrane fractions, however, contain an additional higher molecular weight immunoreactive protein. Reverse transcription-PCR analysis did not show additional longer transcripts that could encode the larger protein. Enzymatic deglycosylation of the membrane preparations converted both immunoreactive proteins into a single faster migrating band, consistent with two states of glycosylation of Na(v)1.9. The developmental change in the glycosylation state of Na(v)1.9 is paralleled by a developmental change in the gating of the persistent TTX-R Na(+) current attributable to Na(v)1.9 in native DRG neurons. Whole-cell patch-clamp analysis demonstrates that the midpoint of steady-state inactivation is shifted 7 mV in a hyperpolarized direction in neonatal (postnatal days 0-3) compared with adult DRG neurons, although there is no significant difference in activation. Pretreatment of neonatal DRG neurons with neuraminidase causes an 8 mV depolarizing shift in the midpoint of steady-state inactivation of Na(v)1.9, making it indistinguishable from that of adult DRG neurons. Our data show that extensive glycosylation of rat Na(v)1.9 is developmentally regulated and changes a critical property of this channel in native neurons.

  4. Effects of sciatic nerve transection on glucose uptake in the presence and absence of lactate in the frog dorsal root ganglia and spinal cord

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    F Rigon

    Full Text Available Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT, which mimics the clinical symptoms of “phantom limb”, a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT.

  5. Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain.

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    Shigeo Hasegawa

    Full Text Available BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2 (cPLA(2 in injured dorsal root ganglion (DRG neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2 activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha and interleukin-1beta (IL-1beta expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain.

  6. Paclitaxel-induced painful neuropathy is associated with changes in mitochondrial bioenergetics, glycolysis, and an energy deficit in dorsal root ganglia neurons.

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    Duggett, Natalie A; Griffiths, Lisa A; Flatters, Sarah J L

    2017-08-01

    Painful neuropathy is the major dose-limiting side effect of paclitaxel chemotherapy. Mitochondrial dysfunction and adenosine triphosphate (ATP) deficit have previously been shown in peripheral nerves of paclitaxel-treated rats, but the effects of paclitaxel in the dorsal root ganglia (DRGs) have not been explored. The aim of this study was to determine the bioenergetic status of DRG neurons following paclitaxel exposure in vitro and in vivo. Utilising isolated DRG neurons, we measured respiratory function under basal conditions and at maximal capacity, glycolytic function, and Adenosine diphosphate (ADP)/ATP levels at 3 key behavioural timepoints; prior to pain onset (day 7), peak pain severity and pain resolution. At day 7, maximal respiration and spare reserve capacity were significantly decreased in DRG neurons from paclitaxel-treated rats. This was accompanied by decreased basal ATP levels and unaltered ADP levels. At peak pain severity, respiratory function was unaltered, yet glycolytic function was significantly increased. Reduced ATP and unaltered ADP levels were also observed at the peak pain timepoint. All these effects in DRG neurons had dissipated by the pain resolution timepoint. None of these paclitaxel-evoked changes could be replicated from in vitro paclitaxel exposure to naive DRG neurons, demonstrating the impact of in vivo exposure and the importance of in vivo models. These data demonstrate the nature of mitochondrial dysfunction evoked by in vivo paclitaxel in the DRG for the first time. Furthermore, we have identified paclitaxel-evoked changes in the bioenergetics of DRG neurons, which result in a persistent energy deficit that is causal to the development and maintenance of paclitaxel-induced pain.

  7. A multicenter, prospective trial to assess the safety and performance of the spinal modulation dorsal root ganglion neurostimulator system in the treatment of chronic pain.

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    Liem, Liong; Russo, Marc; Huygen, Frank J P M; Van Buyten, Jean-Pierre; Smet, Iris; Verrills, Paul; Cousins, Michael; Brooker, Charles; Levy, Robert; Deer, Timothy; Kramer, Jeffery

    2013-01-01

    This multicenter prospective trial was conducted to evaluate the clinical performance of a new neurostimulation system designed to treat chronic pain through the electrical neuromodulation of the dorsal root ganglia (DRG) neurophysiologically associated with painful regions of the limbs and/or trunk. Thirty-two subjects were implanted with a novel neuromodulation device. Pain ratings during stimulation were followed up to six months and compared with baseline ratings. Subjects also completed two separate reversal periods in which stimulation was briefly stopped in order to establish the effects of the intervention. At all assessments, more than half of subjects reported pain relief of 50% or better. At six months postimplant, average overall pain ratings were 58% lower than baseline (p reduction in pain specific to back, leg, and foot regions were 57%, 70%, and 89%, respectively. When stimulation was discontinued for a short time, pain returned to baseline levels. Discrete coverage of hard-to-treat areas was obtained across a variety of anatomical pain distributions. Paresthesia intensity remained stable over time and there was no significant difference in the paresthesia intensity perceived during different body postures/positions (standing up vs. lying down). Results of this clinical trial demonstrate that neurostimulation of the DRG is a viable neuromodulatory technique for the treatment of chronic pain. Additionally, the capture of discrete painful areas such as the feet combined with stable paresthesia intensities across body positions suggest that this stimulation modality may allow more selective targeting of painful areas and reduce unwanted side-effects observed in traditional spinal cord stimulation (SCS). © 2013 International Neuromodulation Society.

  8. Direct effects of HIV-1 Tat on excitability and survival of primary dorsal root ganglion neurons: possible contribution to HIV-1-associated pain.

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    Xianxun Chi

    Full Text Available 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 possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG neurons. We demonstrated that HIV-1 Tat triggered rapid and sustained enhancement of the excitability of small-diameter rat primary DRG neurons, which was accompanied by marked reductions in the rheobase and resting membrane potential (RMP, and an increase in the resistance at threshold (R(Th. Such Tat-induced DRG hyperexcitability may be a consequence of the inhibition of cyclin-dependent kinase 5 (Cdk5 activity. Tat rapidly inhibited Cdk5 kinase activity and mRNA production, and roscovitine, a well-known Cdk5 inhibitor, induced a very similar pattern of DRG hyperexcitability. Indeed, pre-application of Tat prevented roscovitine from having additional effects on the RMP and action potentials (APs of DRGs. However, Tat-mediated actions on the rheobase and R(Th were accelerated by roscovitine. These results suggest that Tat-mediated changes in DRG excitability are partly facilitated by Cdk5 inhibition. In addition, Cdk5 is most abundant in DRG neurons and participates in the regulation of pain signaling. We also demonstrated that HIV-1 Tat markedly induced apoptosis of primary DRG neurons after exposure for longer than 48 h. Together, this work indicates that HIV-1 proteins are capable of producing pain signaling through direct actions on excitability and survival of sensory neurons.

  9. Dorsal root ganglion neurons with dichotomizing axons projecting to the hip joint and the knee skin in rats: possible mechanism of referred knee pain in hip joint disease.

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    Miura, Yoko; Ohtori, Seiji; Nakajima, Takayuki; Kishida, Shinji; Harada, Yoshitada; Takahashi, Kazuhisa

    2011-11-01

    Patients who have hip joint diseases sometimes complain of knee pain as well as hip joint area pain. However, the precise sensory innervation pattern and correlation of the sensory nerves of the hip joint and knee are unknown. The purpose of this study was to investigate dorsal root ganglion (DRG) neurons with dichotomizing axons projecting to both the hip joint and the knee skin in rats using double fluorescent labeling techniques, and to examine characteristics of the DRG neurons with dichotomizing axons using immunohistochemical staining for inflammatory neuropeptides such as calcitonin gene-related peptide (CGRP). For 20 rats, two kinds of neurotracers, Fluoro-Gold (FG) and 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI), were used in the double-labeling study. FG was injected into the left hip joint, and DiI was applied to the left medial portion of knee skin. Ten days after application, bilateral DRGs were harvested and immunohistochemically stained for CGRP. DRG neurons double labeled with FG and DiI were observed only from L2 to L4 on the left side. Approximately 1.6% of all DRG neurons innervating the hip joints had other axons that extended to the medial portion of knee skin, and 35% of double-labeled neurons were CGRP positive. Our results showed that the double-labeled neurons had peripheral axons that dichotomized into both the hip joint and the knee skin. CGRP-positive neurons of these dichotomizing fibers may play some role in the manifestation of referred knee pain with hip joint pain.

  10. Plasticity of dorsal root ganglion neurons in a rat model of post-infectious gut dysfunction: potential implication of nerve growth factor.

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    Jardí, Ferran; Fernández-Blanco, Joan A; Martínez, Vicente; Vergara, Patri

    2014-11-01

    Intestinal infections are suggested as a risk factor for the development of irritable bowel syndrome (IBS)-like visceral hypersensitivity. The mechanisms implicated might involve long-term changes in visceral afferents, with implication of nerve growth factor (NGF). We explored plastic changes in dorsal root ganglia (DRGs) receiving innervation from the gut and the potential implication of NGF in a rat model of IBS-like post-infectious gut dysfunction. Rats were infected with Trichinella spiralis larvae. Thirty days post-infection, inflammatory markers, including interleukins (ILs) and mucosal mast cell infiltration (rat mast cell protease II [RMCPII]), and NGF and TrkA expression was determined in the jejunum and colon (RT-qPCR). In the same animals, morphometry (neuronal body size) and NGF content (immunofluorescence) were assessed in thoracolumbar DRG neurons. In infected animals, a low-grade inflammatory-like response, characterized by up-regulated levels of RMCPII and IL-6, was observed in the jejunum and colon. TrkA expression was increased in the jejunum, whereas the colon showed a slight reduction. NGF levels remained unaltered regardless the gut region. Overall, the mean cross-sectional area of DRG neurons was increased in T. spiralis-infected animals, with a reduction in both TrkA and NGF staining. Results suggest that during T. spiralis infection in rats, there is a remodeling of sensory afferents that might imply a NGF-mediated mechanism. Plastic changes in sensory afferents might mediate the long-lasting functional alterations that characterize this model of IBS. Similar mechanisms might be operating in patients with post-infectious-IBS.

  11. The effects of neuroleptics on the GABA-induced Cl- current in rat dorsal root ganglion neurons: differences between some neuroleptics.

    Science.gov (United States)

    Yokota, Kenjiro; Tatebayashi, Hideharu; Matsuo, Tadashi; Shoge, Takashi; Motomura, Haruhiko; Matsuno, Toshiyuki; Fukuda, Akira; Tashiro, Nobutada

    2002-03-01

    1. Several neuroleptics inhibited the 3 microM gamma-aminobutyric acid induced-chloride current (GABA-current) on dissociated rat dorsal root ganglion neurons in whole-cell patch-clamp investigations. 2. The IC(50) for clozapine, zotepine, olanzapine, risperidone and chlorpromazine were 6.95, 18.26, 20.30, 106.01 and 114.56 microM, respectively. The values for the inhibitory effects of neuroleptics on the GABA (3 microM)-current, which were calculated by the fitting Hill's equations where the concentrations represent the mean therapeutic blood concentrations, were ranked clozapine>zotepine>chlorpromazine>olanzapine>risperidone. These inhibitory effects, weighted with the therapeutic concentrations of neuroleptics, were correlated with the clinical incidences of seizure during treatment with neuroleptics. 3. Clozapine reduced the picrotoxin-inhibiton, and may compete with a ligand of the t-butylbicyclophosphorothionate (TBPS) binding site. 4. Haloperidol and quetiapine did not affect the peak amplitude of the GABA (3 microM)-current. However, haloperidol reduced the clozapine-inhibition, and may antagonize ligand binding to TBPS binding site. 5. Neuroleptics including haloperidol and quetiapine enhanced the desensitization of the GABA (3 microM)-current. However, haloperidol and quetiapine at 100 microM inhibited the desensitization at the beginning of application. 6. Blonanserin (AD-5423) at 30 and 50 microM potentiated the GABA (3 microM)-current to 170.1+/-6.9 and 192.0+/-10.6% of the control current, respectively. Blonanserin shifted GABA concentration-response curve leftward. Blonanserin only partly negatively interacted with diazepam. The blonanserin-potentiation was not reversed by flumazenil. Blonanserin is not a benzodiazepine receptor agonist. 7. The various effects of neuroleptics on the GABA-current may be related to the clinical effects including modifying the seizure threshold.

  12. The effects of neuroleptics on the GABA-induced Cl− current in rat dorsal root ganglion neurons: differences between some neuroleptics

    Science.gov (United States)

    Yokota, Kenjiro; Tatebayashi, Hideharu; Matsuo, Tadashi; Shoge, Takashi; Motomura, Haruhiko; Matsuno, Toshiyuki; Fukuda, Akira; Tashiro, Nobutada

    2002-01-01

    Several neuroleptics inhibited the 3 μM γ-aminobutyric acid induced-chloride current (GABA-current) on dissociated rat dorsal root ganglion neurons in whole-cell patch-clamp investigations. The IC50 for clozapine, zotepine, olanzapine, risperidone and chlorpromazine were 6.95, 18.26, 20.30, 106.01 and 114.56 μM, respectively. The values for the inhibitory effects of neuroleptics on the GABA (3 μM)-current, which were calculated by the fitting Hill's equations where the concentrations represent the mean therapeutic blood concentrations, were ranked clozapine>zotepine>chlorpromazine>olanzapine>risperidone. These inhibitory effects, weighted with the therapeutic concentrations of neuroleptics, were correlated with the clinical incidences of seizure during treatment with neuroleptics. Clozapine reduced the picrotoxin-inhibiton, and may compete with a ligand of the t-butylbicyclophosphorothionate (TBPS) binding site. Haloperidol and quetiapine did not affect the peak amplitude of the GABA (3 μM)-current. However, haloperidol reduced the clozapine-inhibition, and may antagonize ligand binding to TBPS binding site. Neuroleptics including haloperidol and quetiapine enhanced the desensitization of the GABA (3 μM)-current. However, haloperidol and quetiapine at 100 μM inhibited the desensitization at the beginning of application. Blonanserin (AD-5423) at 30 and 50 μM potentiated the GABA (3 μM)-current to 170.1±6.9 and 192.0±10.6% of the control current, respectively. Blonanserin shifted GABA concentration-response curve leftward. Blonanserin only partly negatively interacted with diazepam. The blonanserin-potentiation was not reversed by flumazenil. Blonanserin is not a benzodiazepine receptor agonist. The various effects of neuroleptics on the GABA-current may be related to the clinical effects including modifying the seizure threshold. PMID:11906969

  13. Ca2+ channel currents in dorsal root ganglion neurons of P/Q-type voltage-gated Ca2+ channel mutant mouse, rolling mouse Nagoya.

    Science.gov (United States)

    Fukumoto, Nao; Kitamura, Naoki; Niimi, Kimie; Takahashi, Eiki; Itakura, Chitoshi; Shibuya, Izumi

    2012-07-01

    The role of the P/Q-type voltage-gated Ca(2+) channels (VGCCs) in release of neurotransmitters involved in nociception is not fully understood. Rolling mouse Nagoya (tg(rol)), a P/Q-type channel mutant mouse, expresses P/Q-type VGCC whose activation curve has a higher half activation potential and a smaller slope factor than the wild type channel. We previously reported that tg(rol) mice showed hypoalgesic responses to noxious stimuli. In this study, we examined the VGCC current in dorsal root ganglion (DRG) neurons by the whole-cell patch-clamp method. Both ω-agatoxin IVA (0.1 μM) and ω-conotoxin GVIA (1 μM) inhibited the VGCC current by about 40-50% in both the homozygous tg(rol) (tg(rol)/tg(rol)) and wild type (+/+) mice. The voltage-activation relationships of the total VGCC current and the ω-agatoxin IVA-sensitive component in the tg(rol)/tg(rol) mice shifted positively compared to the +/+ mice, whereas that sensitive to the ω-conotoxin GVIA was not different between the two genotypes. The time constant of activation of the VGCC current at -20 mV was longer in the tg(rol)/tg(rol) mice than in the +/+ mice. These changes in the properties of the VGCC in the tg(rol)/tg(rol) mouse may reduce the amount of the released neurotransmitters and account for the hypoalgesic responses. Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  14. Modulation of dragon's blood on tetrodotoxin-resistant sodium currents in dorsal root ganglion neurons and identification of its material basis for efficacy.

    Science.gov (United States)

    Liu, Xiangming; Chen, Su; Zhang, Yuxia; Zhang, Fan

    2006-06-01

    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 loureirin B) extracted from dragon's blood on the TTX-R sodium currents in acute-isolated DRG neurons of rats were observed. According to the operational definition of material basis for the efficacy of TCM established, the material basis of the modulation on the TTX-R sodium currents in DRG neurons of dragon's blood was judged from the experimental results. The drug interaction equation of Greco et al. was used to assess the interaction of the three components extracted from dragon's blood. This investigation demonstrated that dragon's blood suppressed the peak TTX-R sodium currents in a dose-dependent way and affected the activations of TTX-R sodium currents. The effects of the combination of cochinchinenin A, cochinchinenin B, and loureirin B were in good agreement with those of dragon's blood. Although the three components used alone could modulate TTX-R sodium currents, the concentrations of the three components used alone were respectively higher than those used in combination when the inhibition rates on the TTX-R sodium currents of them used alone and in combination were the same. The combined effects of the three components were synergistic. These results suggested that the interference with pain messages caused by the modulation of dragon's blood on TTX-R sodium currents in DRG neurons may explain some of the analgesic effect of dragon's blood and the corresponding material basis for the efficacy is the combination of cochinchinenin A, cochinchinenin B, and loureirin B.

  15. Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

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    Takayoshi eMasuoka

    2016-03-01

    Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

  16. Pain-related behavior and the characteristics of dorsal-root ganglia in a rat model of hip osteoarthritis induced by mono-iodoacetate.

    Science.gov (United States)

    Miyamoto, Shuichi; Nakamura, Junichi; Ohtori, Seiji; Orita, Sumihisa; Nakajima, Takayuki; Omae, Takanori; Hagiwara, Shigeo; Takazawa, Makoto; Suzuki, Miyako; Suzuki, Takane; Takahashi, Kazuhisa

    2017-07-01

    The principal aim of this study was to clarify the time course of pain-related behavior and pain-related sensory innervation in a rat model of hip osteoarthritis (OA) induced by intra-articular injection of mono-iodoacetate (MIA). Using 6-week-old male Sprague Dawley rats, 25 μl of sterile saline of 1% Fluoro-Gold solution (FG) (control group; n = 30) and 25 μl of sterile saline of 1% FG with 2 mg of MIA (MIA group; n = 30) was injected into the right hip joints. Gait function was evaluated using a CatWalk system after 7, 14, 28, 42, and 56 days (n = 5, respectively). Neurons in the dorsal root ganglion (DRG) between L1 and L5 were immunostained for calcitonin gene-related peptide (CGRP) and activating transcription factor-3 (ATF3). Gait analysis revealed the mean six parameters of hind paws at all time points were significantly lower in the MIA group (p = 0.05). The number of CGRP-immunoreactive (-IR) DRG neurons was significantly increased on days 7, 14, 28, and 42 peaking at 14 days in the MIA group. By contrast, expression of ATF3-IR in FG-labeled DRG neurons was significantly increased on days 42 and 57. The FG-labeled DRG neurons were distributed between L1 and L5, mainly at the L4 level. Pain-related behavior indicated by gait disturbance was observed in a MIA model of hip OA in rat. Early elevation of CGRP expression and late expression of ATF-3 were demonstrated in DRG neurons, possibly reflecting inflammatory pain and neuropathic pain in hip OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1424-1430, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. Varicella-zoster virus glycoprotein I is essential for spread in dorsal root ganglia and facilitates axonal localization of structural virion components in neuronal cultures.

    Science.gov (United States)

    Christensen, Jenna; Steain, Megan; Slobedman, Barry; Abendroth, Allison

    2013-12-01

    Neurons of the sensory ganglia are the major site of varicella-zoster virus (VZV) latency and may undergo productive infection during reactivation. Although the VZV glycoprotein E/glycoprotein I (gE/gI) complex is known to be critical for neurovirulence, few studies have assessed the roles of these proteins during infection of dorsal root ganglia (DRG) due to the high human specificity of the virus. Here, we show that the VZV glycoprotein I gene is an important neurotropic gene responsible for mediating the spread of virus in neuronal cultures and explanted DRG. Inoculation of differentiated SH-SY5Y neuronal cell cultures with a VZV gI gene deletion strain (VZV rOkaΔgI) showed a large reduction in the percentage of cells infected and significantly smaller plaque sizes in a comparison with cultures infected with the parental strain (VZV rOka). In contrast, VZV rOkaΔgI was not significantly attenuated in fibroblast cultures, demonstrating a cell type-specific role for VZV gI. Analysis of rOkaΔgI protein localization by immunofluorescent staining revealed aberrant localization of viral glycoprotein and capsid proteins, with little or no staining present in the axons of differentiated SH-SY5Y cells infected with rOkaΔgI, yet axonal vesicle trafficking was not impaired. Further studies utilizing explanted human DRG indicated that VZV gI is required for the spread of virus within DRG. These data demonstrate a role for VZV gI in the cell-to-cell spread of virus during productive replication in neuronal cells and a role in facilitating the access of virion components to axons.

  18. Pericellular Griffonia simplicifolia I isolectin B4-binding ring structures in the dorsal root ganglia following peripheral nerve injury in rats.

    Science.gov (United States)

    Li, L; Zhou, X F

    2001-10-22

    Patients with a peripheral nerve injury often suffer from persistent chronic pain, but the underlying mechanism remains largely unknown. The persistent nature of the pain suggests injury-induced profound structural changes along the sensory pathways. In the present study, using the plant Griffonia simplicifolia I isolectin B4 (IB4) as a marker for nonpeptidergic small sensory neurons, we sought to examine whether these neurons sprout in the dorsal root ganglia (DRG) in response to peripheral nerve injury. The lumbar 5 (L5) spinal nerve was transected, and rats were allowed to survive for varying lengths of time before IB4 histology was performed. We found that a subpopulation of IB4-positive sensory neurons sprouted robustly after spinal nerve injury. Twelve weeks after spinal nerve injury, the IB4-positive ring structures became dramatic and encircled both large and small neurons in the DRG. The aberrant sprouting of small sensory neurons was also demonstrated by retrograde labeling. The processes of satellite cells surrounding large sensory neurons also became IB4 positive, and 87.8% of perineuronal IB4-positive ring structures intermingled and/or coexpressed with glial fibrillary acidic protein-positive satellite cells. Thus, the sprouting axons of IB4-positive neurons were intermingled with IB4-positive satellite cells, forming perineuronal ring structures surrounding large-diameter neurons. Ultrastructural examinations further confirmed that IB4-positive nerve terminals were entangled with satellite cells and IB4-negative unmyelinated sprouting fibers around sensory neurons. These studies have provided the first evidence that a subpopulation of IB4-binding small sensory neurons sprouts and forms perineuronal ring structures together with IB4-positive satellite cells in response to nerve injury. The significance of the sprouting of IB4-positive neurons remains to be determined. Copyright 2001 Wiley-Liss, Inc.

  19. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

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    Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

    2010-07-16

    Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: 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 extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  20. Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts In Vivo.

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    Leigh Zerboni

    2015-06-01

    Full Text Available Varicella zoster virus (VZV, a human alphaherpesvirus, causes varicella during primary infection. VZV reactivation from neuronal latency may cause herpes zoster, post herpetic neuralgia (PHN and other neurologic syndromes. To investigate VZV neuropathogenesis, we developed a model using human dorsal root ganglia (DRG xenografts in immunodeficient (SCID mice. The SCID DRG model provides an opportunity to examine characteristics of VZV infection that occur in the context of the specialized architecture of DRG, in which nerve cell bodies are ensheathed by satellite glial cells (SGC which support neuronal homeostasis. We hypothesized that VZV exhibits neuron-subtype specific tropism and that VZV tropism for SGC contributes to VZV-related ganglionopathy. Based on quantitative analyses of viral and cell protein expression in DRG tissue sections, we demonstrated that, whereas DRG neurons had an immature neuronal phenotype prior to implantation, subtype heterogeneity was observed within 20 weeks and SGC retained the capacity to maintain neuronal homeostasis longterm. Profiling VZV protein expression in DRG neurons showed that VZV enters peripherin+ nociceptive and RT97+ mechanoreceptive neurons by both axonal transport and contiguous spread from SGC, but replication in RT97+ neurons is blocked. Restriction occurs even when the SGC surrounding the neuronal cell body were infected and after entry and ORF61 expression, but before IE62 or IE63 protein expression. Notably, although contiguous VZV spread with loss of SGC support would be predicted to affect survival of both nociceptive and mechanoreceptive neurons, RT97+ neurons showed selective loss relative to peripherin+ neurons at later times in DRG infection. Profiling cell factors that were upregulated in VZV-infected DRG indicated that VZV infection induced marked pro-inflammatory responses, as well as proteins of the interferon pathway and neuroprotective responses. These neuropathologic changes

  1. Antinociceptive Effects of AGAP, a Recombinant Neurotoxic Polypeptide: Possible Involvement of the Tetrodotoxin-Resistant Sodium Channels in Small Dorsal Root Ganglia Neurons

    Science.gov (United States)

    Li, Chun-Li; Liu, Xi-Fang; Li, Gui-Xia; Ban, Meng-qi; Chen, Jian-Zhao; Cui, Yong; Zhang, Jing-Hai; Wu, Chun-Fu

    2016-01-01

    Antitumor-analgesic peptide (AGAP) is a novel recombinant polypeptide. The primary study showed that AGAP 1.0 mg/kg exhibited strong analgesic and antitumor effects. The tail vein administration of AGAP potently reduced pain behaviors in mice induced by intraplantar injection of formalin or intraperitoneal injection of acetic acid, without affecting basal pain perception. To further assess the mechanisms of AGAP, the effects of AGAP on sodium channels were assessed using the whole-cell patch clamp recordings in dorsal root ganglia (DRG) neurons. The results showed that AGAP (3–1000 nM) inhibited the sodium currents in small-diameter DRG neurons in a dose-dependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve of sodium channels in a voltage-dependent manner and negatively shift the activation curves. 1000 nM AGAP could reduce the tetrodotoxin-resistant (TTX-R) sodium currents by 42.8% in small-diameter DRG neurons. Further analysis revealed that AGAP potently inhibited NaV1.8 currents by 59.4%, and negatively shifted the activation and inactivation kinetics. 1000 nM AGAP also reduced the NaV1.9 currents by 33.7%, but had no significant effect on activation and inactivation kinetics. Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons. It is concluded that these new results may better explain, at least in part, the analgesic properties of this polypeptide. PMID:28066245

  2. Regulation of the Spontaneous Augmentation of NaV1.9 in Mouse Dorsal Root Ganglion Neurons: Effect of PKA and PKC Pathways

    Science.gov (United States)

    Kakimura, Jun-ichi; Zheng, Taixing; Uryu, Noriko; Ogata, Nobukuni

    2010-01-01

    Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R) isoforms of voltage-gated sodium channels, NaV1.8 and NaV1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is NaV1.9: our previous studies revealed a unique property of the NaV1.9 current, i.e., the NaV1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording (“spontaneous augmentation of NaV1.9”). However, the mechanism underlying the spontaneous augmentation of NaV1.9 is still unclear. In this study, we examined the effects of protein kinases A and C (PKA and PKC), on the spontaneous augmentation of NaV1.9. The spontaneous augmentation of the NaV1.9 current was significantly suppressed by activation of PKA, whereas activation of PKA did not affect the voltage dependence of inactivation for the NaV1.9 current. On the contrary, the finding that activation of PKC can affect the voltage dependence of inactivation for NaV1.9 in the perforated patch recordings, where the augmentation does not occur, suggests that the effects of PMA are independent of the augmentation process. These results indicate that the spontaneous augmentation of NaV1.9 was regulated directly by PKA, and indirectly by PKC. PMID:20411123

  3. Antinociceptive effects of AGAP, a recombinant neurotoxic polypeptide: Possible involvement of the tetrodotoxin-resistant sodium channels in small dorsal root ganglia neurons

    Directory of Open Access Journals (Sweden)

    Li Chunli

    2016-12-01

    Full Text Available Antitumor-analgesic peptide(AGAP)is a novel recombinant polypeptide. The primary study showed that AGAP 1.0 mg/kg exhibited strong analgesic and antitumor effects. The tail vein administration of AGAP potently reduced pain behaviors in mice induced by intraplantar injection of formalin or intraperitoneal injection of acetic acid, without affecting basal pain perception. To further assess the mechanisms of AGAP, the effects of AGAP on sodium channels were assessed using the whole-cell patch clamp recordings in dorsal root ganglia (DRG neurons. The results showed that AGAP (3-1000 nM inhibited the sodium currents in small-diameter DRG neurons in a dose-dependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve of sodium channels in a voltage-dependent manner and negatively shift the activation curves. 1000 nM AGAP could reduce the tetrodotoxin-resistant (TTX-R sodium currents by 42.8% in small-diameter DRG neurons. Further analysis revealed that AGAP potently inhibited NaV1.8 currents by 59.4%, and negatively shifted the activation and inactivation kinetics. 1000 nM AGAP also reduced the NaV1.9 currents by 33.7%, but had no significant effect on activation and inactivation kinetics. Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons. It is concluded that these new results may better explain, at least in part, the analgesic properties of this polypeptide.

  4. Comparative study of voltage-gated sodium channel α-subunits in non-overlapping four neuronal populations in the rat dorsal root ganglion.

    Science.gov (United States)

    Fukuoka, Tetsuo; Noguchi, Koichi

    2011-06-01

    Voltage-gated sodium channel α-subunit (Nav) is the major determinant of neuronal electrophysiological characters. In order to compare the composition of Navs among neurochemically different neurons in the rat dorsal root ganglion (DRG), we examined the expression of Nav transcripts in four non-overlapping neuronal populations, with (+) or without (-) N52 immunoreactivity, a marker of neurons with myelinated axons, and TrkA mRNA identified by in situ hybridization histochemistry. Both N52-/TrkA+ and N52-/TrkA- populations had high levels of signals for Nav1.7, Nav1.8, and Nav1.9 mRNAs, but rarely expressed Nav1.1 or Nav1.6. There was no significant difference in these signals, suggesting that C-fiber peptidergic and non-peptidergic neurons have similar electrophysiological characters with regard to sodium currents. N52+/TrkA+ neurons (putative A-fiber nociceptors) had similar high levels of signals for Nav1.7 and Nav1.8, but a significantly lower level of Nav1.9 signals, as compared to N52- neurons. Although, almost no N52+/TrkA- neurons had Nav1.8 or Nav1.9, half of this population expressed Nav1.7 at similar levels to other three populations and the other half completely lacked this channel. These data suggest that Nav1.8 is a common channel for both C- and A-fiber nociceptors, and Nav1.9 is rather selective for C-fiber nociceptors. Nav1.7 is the most universal channel while some functionally unknown N52+/TrkA- subpopulation selectively lacks it. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  5. Cisplatin-induced neuropathic pain is mediated by upregulation of N-type voltage-gated calcium channels in dorsal root ganglion neurons.

    Science.gov (United States)

    Leo, Markus; Schmitt, Linda-Isabell; Erkel, Martin; Melnikova, Margarita; Thomale, Jürgen; Hagenacker, Tim

    2017-02-01

    Cisplatin is important in the treatment of various types of cancer. Although it is highly effective, it also has severe side effects, with neurotoxicity in dorsal root ganglion (DRG) neurons being one of the most common. The key mechanisms of neurotoxicity are still controversially discussed; however, disturbances of the calcium homeostasis in DRG neurons have been suggested to mediate cisplatin neurotoxicity. By using the whole-cell patch-clamp technique, immunostaining and behavioral experiments with Sprague-Dawley rats, we examined the influence of short- and long-term exposure to cisplatin on voltage-gated calcium channel (VGCC) currents (ICa(V)) in small DRG neurons. In vitro exposure to cisplatin reduced ICa(V) in a concentration-dependent manner (0.01-50μM; 13.8-77.3%; IC50 5.07μM). Subtype-specific measurements of VGCCs showed differential effects on ICa(V). While the ICa(V) of P/Q-, L- and T-type VGCCs were reduced, ICa(V) of N-type VGCCs were increased by 30.3% during depolarization to 0mV. Exposure of DRG neurons to cisplatin (0.5 or 5μM) for 24-48h in vitro significantly increased a CaMK II-mediated ICa(V) current density. Immunostaining and western blot analysis revealed an increase of N-type VGCC protein level in DRG neurons 24h after cisplatin exposure. Cisplatin-mediated activation of caspase-3 was prevented by inhibition of N-type VGCCs using Ɯ-conotoxin MVIIA. Behavioral experiments showed that Ɯ-conotoxin MVIIA treatment prevented neuropathic syndromes in vivo by inhibiting upregulation of the N-type protein level. Here we show evidence for the first time for a crucial role of N-type VGCC in the genesis of cisplatin-induced polyneuropathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Oxaliplatin-induced changes in expression of transient receptor potential channels in the dorsal root ganglion as a neuropathic mechanism for cold hypersensitivity.

    Science.gov (United States)

    Chukyo, Akiko; Chiba, Terumasa; Kambe, Toshie; Yamamoto, Ken; Kawakami, Kazuyoshi; Taguchi, Kyoji; Abe, Kenji

    2017-12-15

    Transient receptor potential (TRP) receptors are involved in the development of chemotherapy-induced peripheral neuropathic pain, which is a common side effect of selected chemotherapeutic agents such as oxaliplatin. However, the precise contribution of TRPs to this condition remains unknown. Cold hypersensitivity is the hallmark of oxaliplatin-induced neuropathy, so we used a preclinical model of oxaliplatin-induced cold hypersensitivity in rats to determine the effects of oxaliplatin on TRP channels. To this end, immunohistochemistry was used to examine TRP vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and TRP melastatin 8 (TRPM8) expression in the rat dorsal root ganglion (DRG) after 4days of oxaliplatin treatment. Behavioral assessment using the acetone spray test showed that oxaliplatin significantly increased acute cold hypersensitivity after 4days of treatment. Double-staining immunohistochemistry showed that 4days after oxaliplatin treatment, there was increased co-expression of TRPA1 and TRPV1 in isolectin B4-positive small-sized DRG neurons, as well as a significant increase in the co-localization of TRPM8 and neurofilament 200 in medium-sized DRG neurons. In addition, in situ hybridization revealed that TRPV1 protein was co-expressed with TRPA1 mRNA on day 4 after oxaliplatin administration. Thus, at an early stage following oxaliplatin treatment there is an increased expression of TRPA1 and TRPV1 in small-sized DRG neurons and of TRPM8 in medium-sized DRG neurons. Collectively, these changes may contribute to the development of oxaliplatin-induced peripheral neuropathic pain. Copyright © 2017. Published by Elsevier Ltd.

  7. Regulation of the Spontaneous Augmentation of NaV1.9 in Mouse Dorsal Root Ganglion Neurons: Effect of PKA and PKC Pathways

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    Nobukuni Ogata

    2010-03-01

    Full Text Available Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R isoforms of voltage-gated sodium channels, NaV1.8 and NaV1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is NaV1.9: our previous studies revealed a unique property of the NaV1.9 current, i.e., the NaV1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording (“spontaneous augmentation of NaV1.9”. However, the mechanism underlying the spontaneous augmentation of NaV1.9 is still unclear. In this study, we examined the effects of protein kinases A and C (PKA and PKC, on the spontaneous augmentation of NaV1.9. The spontaneous augmentation of the NaV1.9 current was significantly suppressed by activation of PKA, whereas activation of PKA did not affect the voltage dependence of inactivation for the NaV1.9 current. On the contrary, the finding that activation of PKC can affect the voltage dependence of inactivation for NaV1.9 in the perforated patch recordings, where the augmentation does not occur, suggests that the effects of PMA are independent of the augmentation process. These results indicate that the spontaneous augmentation of NaV1.9 was regulated directly by PKA, and indirectly by PKC.

  8. Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

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    Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

    2009-10-01

    Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

  9. Activation of the RAGE/STAT3 Pathway in the Dorsal Root Ganglion Contributes to the Persistent Pain Hypersensitivity Induced by Lumbar Disc Herniation.

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    Zhang, Xin-Sheng; Li, Xiao; Luo, Hai-Jie; Huang, Zhu-Xi; Liu, Cui-Cui; Wan, Qing; Xu, Shu-Wei; Wu, Shao-Ling; Ke, Song-Jian; Ma, Chao

    2017-07-01

    Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. Controlled animal study. University laboratory. After LDH induced by implantation of autologous nucleus pulposus (NP, harvested from animal tail) on the left L5 nerve root was established, mechanical thresholds and electrophysiological tests were conducted at relevant time points during an observation period of 28 days. Protein levels and localization of RAGE and p-STAT3 were performed by using Western blotting and immunohistochemistry, respectively. LDH induced persistent pain hypersensitivity, increased excitability of DRG neurons, and upregulated the expression of RAGE and p-STAT3 in the DRG. Consecutive injection of both RAGE antagonist FPS-ZM1 (i.t.) and STAT3 activity inhibitor S3I-201 (i.t.) inhibited the enhanced excitability of DRG neurons and mechanical allodynia induced by NP implantation. Furthermore, local knockdown of STAT3 by intrathecal injection of AAV-Cre-GFP into STAT3flox/flox mice markedly alleviated NP implantation-induced mechanical allodynia in mice. Importantly, the expression of p-STAT3 was colocalized with that of RAGE in the DRG and inhibition of RAGE with FPS-ZM1 prevented NP implantation-induced STAT3 activation. More underlying mechanism(s) of the role of the RAGE/STAT3 pathway on the formation and development of persistent pain hypersensitivity induced by LDH will be needed to be explored in future research. These findings suggest activation of the RAGE/STAT3 pathway plays a critical role in persistent pain induced by LDH, and this pathway may represent novel therapeutic targets for the treatment of LDH

  10. Anti hyperglycemic activities of Annona muricata (Linn).

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    Adeyemi, David Olawale; Komolafe, Omobola Aderibigbe; Adewole, Olarinde Stephen; Obuotor, Efere Martins; Adenowo, Thomas Kehinde

    2008-10-25

    This study was designed to determine the effects of methanolic extracts of Annona muricata (Linn) on the blood glucose level of streptozotocin-induced diabetic Wistar rats. Thirty adult Wistar rats were randomly assigned into three groups (A, B and C) of ten rats each. Group A was the control, Group B was untreated hyperglycemic group and group C was A. muricata-treated group. Hyperglycemia was induced in groups B and C by a single intraperitoneal injection of 80 mg/kg streptozotocin dissolved in 0.1 M citrate buffer. The control group was intraperitoneally injected with equivalent volume of citrate buffer and all the animals were monitored for four weeks. Daily intra peritoneal injection of 100 mg/kg A. muricata was administered to group C rats for two weeks and the animals were monitored for another two weeks. The data obtained were analyzed with descriptive and inferential statistics. The result showed a mean body weight of 206 +/- 7.74 g, 173.29+/-5.13 g and 197 +/- 5.62 g respectively for the control, untreated diabetic and A. muricata-treated diabetic group, and a mean blood glucose concentration of 3.78 +/- 0.190 mmol/L, 21.64 +/- 2.229 mmol/L and 4.22 +/- 0.151 mmol/L for the control, untreated diabetic and treated diabetic groups respectively. A significant difference exists between the blood glucose concentrations of treated and untreated hyperglycemic groups of rats. The result of this study demonstrated that A. muricata possesses anti-hyperglycemic activities.

  11. Bilateral elevation of interleukin-6 protein and mRNA in both lumbar and cervical dorsal root ganglia following unilateral chronic compression injury of the sciatic nerve

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    2013-01-01

    Background Current research implicates interleukin (IL)-6 as a key component of the nervous-system response to injury with various effects. Methods We used unilateral chronic constriction injury (CCI) of rat sciatic nerve as a model for neuropathic pain. Immunofluorescence, ELISA, western blotting and in situ hybridization were used to investigate bilateral changes in IL-6 protein and mRNA in both lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) following CCI. The operated (CCI) and sham-operated (sham) rats were assessed after 1, 3, 7, and 14 days. Withdrawal thresholds for mechanical hyperalgesia and latencies for thermal hyperalgesia were measured in both ipsilateral and contralateral hind and fore paws. Results The ipsilateral hind paws of all CCI rats displayed a decreased threshold of mechanical hyperalgesia and withdrawal latency of thermal hyperalgesia, while the contralateral hind and fore paws of both sides exhibited no significant changes in mechanical or thermal sensitivity. No significant behavioral changes were found in the hind and fore paws on either side of the sham rats, except for thermal hypersensitivity, which was present bilaterally at 3 days. Unilateral CCI of the sciatic nerve induced a bilateral increase in IL-6 immunostaining in the neuronal bodies and satellite glial cells (SGC) surrounding neurons of both lumbar and cervical DRG, compared with those of naive control rats. This bilateral increase in IL-6 protein levels was confirmed by ELISA and western blotting. More intense staining for IL-6 mRNA was detected in lumbar and cervical DRG from both sides of rats following CCI. The DRG removed from sham rats displayed a similar pattern of staining for IL-6 protein and mRNA as found in naive DRG, but there was a higher staining intensity in SGC. Conclusions Bilateral elevation of IL-6 protein and mRNA is not limited to DRG homonymous to the injured nerve, but also extended to DRG that are heteronymous to the injured nerve. The

  12. Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

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    Ghazizadeh, Vahid; Nazıroğlu, Mustafa

    2014-09-01

    Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

  13. Upregulation of casein kinase 1ε in dorsal root ganglia and spinal cord after mouse spinal nerve injury contributes to neuropathic pain

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    Zong Shuqin

    2009-12-01

    Full Text Available Abstract Background Neuropathic pain is a complex chronic pain generated by damage to, or pathological changes in the somatosensory nervous system. Characteristic features of neuropathic pain are allodynia, hyperalgesia and spontaneous pain. Such abnormalities associated with neuropathic pain state remain to be a significant clinical problem. However, the neuronal mechanisms underlying the pathogenesis of neuropathic pain are complex and still poorly understood. Casein kinase 1 is a serine/threonine protein kinase and has been implicated in a wide range of signaling activities such as cell differentiation, proliferation, apoptosis, circadian rhythms and membrane transport. In mammals, the CK1 family consists of seven members (α, β, γ1, γ2, γ3, δ, and ε with a highly conserved kinase domain and divergent amino- and carboxy-termini. Results Preliminary cDNA microarray analysis revealed that the expression of the casein kinase 1 epsilon (CK1ε mRNA in the spinal cord of the neuropathic pain-resistant N- type Ca2+ channel deficient (Cav2.2-/- mice was decreased by the spinal nerve injury. The same injury exerted no effects on the expression of CK1ε mRNA in the wild-type mice. Western blot analysis of the spinal cord identified the downregulation of CK1ε protein in the injured Cav2.2-/- mice, which is consistent with the data of microarray analysis. However, the expression of CK1ε protein was found to be up-regulated in the spinal cord of injured wild-type mice. Immunocytochemical analysis revealed that the spinal nerve injury changed the expression profiles of CK1ε protein in the dorsal root ganglion (DRG and the spinal cord neurons. Both the percentage of CK1ε-positive neurons and the expression level of CK1ε protein were increased in DRG and the spinal cord of the neuropathic mice. These changes were reversed in the spinal cord of the injured Cav2.2-/- mice. Furthermore, intrathecal administration of a CK1 inhibitor IC261 produced

  14. Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

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    Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

    2018-01-01

    Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the

  15. Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression.

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    Fang, Xin; Djouhri, Laiche; McMullan, Simon; Berry, Carol; Waxman, Stephen G; Okuse, Kenji; Lawson, Sally N

    2006-07-05

    Binding to isolectin-B4 (IB4) and expression of tyrosine kinase A (trkA) (the high-affinity NGF receptor) have been used to define two different subgroups of nociceptive small dorsal root ganglion (DRG) neurons. We previously showed that only nociceptors have high trkA levels. However, information about sensory and electrophysiological properties in vivo of single identified IB4-binding neurons, and about their trkA expression levels, is lacking. IB4-positive (IB4+) and small dark neurons had similar size distributions. We examined IB4-binding levels in >120 dye-injected DRG neurons with sensory and electrophysiological properties recorded in vivo. Relative immunointensities for trkA and two TTX-resistant sodium channels (Nav1.8 and Nav1.9) were also measured in these neurons. IB4+ neurons were classified as strongly or weakly IB4+. All strongly IB4+ neurons were C-nociceptor type (C-fiber nociceptive or unresponsive). Of 32 C-nociceptor-type neurons examined, approximately 50% were strongly IB4+, approximately 20% were weakly IB4+ and approximately 30% were IB4-. Adelta low-threshold mechanoreceptive (LTM) neurons were weakly IB4+ or IB4-. All 33 A-fiber nociceptors and all 44 Aalpha/beta-LTM neurons examined were IB4-. IB4+ compared with IB4- C-nociceptor-type neurons had longer somatic action potential durations and rise times, slower conduction velocities, more negative membrane potentials, and greater immunointensities for Nav1.9 but not Nav1.8. Immunointensities of IB4 binding in C-neurons were positively correlated with those of Nav1.9 but not Nav1.8. Of 23 C-neurons tested for both trkA and IB4, approximately 35% were trkA+/IB4+ but with negatively correlated immunointensities; 26% were IB4+/trkA-, and 35% were IB4-/trkA+. We conclude that strongly IB4+ DRG neurons are exclusively C-nociceptor type and that high Nav1.9 expression may contribute to their distinct membrane properties.

  16. The Locus Coeruleus–Norepinephrine System Mediates Empathy for Pain through Selective Up-Regulation of P2X3 Receptor in Dorsal Root Ganglia in Rats

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    Yun-Fei Lü

    2017-09-01

    Full Text Available Empathy for pain (vicariously felt pain, an ability to feel, recognize, understand and share the painful emotions of others, has been gradually accepted to be a common identity in both humans and rodents, however, the underlying neural and molecular mechanisms are largely unknown. Recently, we have developed a rat model of empathy for pain in which pain can be transferred from a cagemate demonstrator (CD in pain to a naïve cagemate observer (CO after 30 min dyadic priming social interaction. The naïve CO rats display both mechanical pain hypersensitivity (hyperalgesia and enhanced spinal nociception. Chemical lesions of bilateral medial prefrontal cortex (mPFC abolish the empathic pain response completely, suggesting existence of a top-down facilitation system in production of empathy for pain. However, the social transfer of pain was not observed in non-cagemate observer (NCO after dyadic social interaction with a non-cagemate demonstrator (NCD in pain. Here we showed that dyadic social interaction with a painful CD resulted in elevation of circulating norepinephrine (NE and increased neuronal activity in the locus coeruleus (LC in the CO rats. Meanwhile, CO rats also had over-expression of P2X3, but not TRPV1, in the dorsal root ganglia (DRG. Chemical lesion of the LC-NE neurons by systemic DSP-4 and pharmacological inhibition of central synaptic release of NE by clonidine completely abolished increase in circulating NE and P2X3 receptor expression, as well as the sympathetically-maintained development of empathic mechanical hyperalgesia. However, in the NCO rats, neither the LC-NE neuronal activity nor the P2X3 receptor expression was altered after dyadic social interaction with a painful NCD although the circulating corticosterone and NE were elevated. Finally, in the periphery, both P2X3 receptor and α1 adrenergic receptor were found to be involved in the development of empathic mechanical hyperalgesia. Taken together with our previous

  17. Effects of estrogens and bladder inflammation on mitogen-activated protein kinases in lumbosacral dorsal root ganglia from adult female rats

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    Keast Janet R

    2009-12-01

    Full Text Available Abstract Background Interstitial cystitis is a chronic condition associated with bladder inflammation and, like a number of other chronic pain states, symptoms associated with interstitial cystitis are more common in females and fluctuate during the menstrual cycle. The aim of this study was to determine if estrogens could directly modulate signalling pathways within bladder sensory neurons, such as extracellular signal-related kinase (ERK and p38 mitogen-activated protein (MAP kinases. These signalling pathways have been implicated in neuronal plasticity underlying development of inflammatory somatic pain but have not been as extensively investigated in visceral nociceptors. We have focused on lumbosacral dorsal root ganglion (DRG neurons projecting to pelvic viscera (L1, L2, L6, S1 of adult female Sprague-Dawley rats and performed both in vitro and in vivo manipulations to compare the effects of short- and long-term changes in estrogen levels on MAPK expression and activation. We have also investigated if prolonged estrogen deprivation influences the effects of lower urinary tract inflammation on MAPK signalling. Results In studies of isolated DRG neurons in short-term (overnight culture, we found that estradiol and estrogen receptor (ER agonists rapidly stimulated ER-dependent p38 phosphorylation relative to total p38. Examination of DRGs following chronic estrogen deprivation in vivo (ovariectomy showed a parallel increase in total and phosphorylated p38 (relative to β-tubulin. We also observed an increase in ERK1 phosphorylation (relative to total ERK1, but no change in ERK1 expression (relative to β-tubulin. We observed no change in ERK2 expression or phosphorylation. Although ovariectomy increased the level of phosphorylated ERK1 (vs. total ERK1, cyclophosphamide-induced lower urinary tract inflammation did not cause a net increase of either ERK1 or ERK2, or their phosphorylation. Inflammation did, however, cause an increase in p38

  18. [Selective cervical dorsal root cutting off part of the vertebral lateral mass fixation combined with exercise therapy for treating spastic cerebral paralysis of the upper limbs caused by cerebral palsy].

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    Zhang, Peng; Hu, Wei; Cao, Xu; Xu, Shi-gang; Li, De-kui; Xu, Lin

    2009-10-01

    To explore the feasibility and the result for the surgical treatment of spastic cerebral paralysis of the upper limbs in patients who underwent the selective cervical dorsal root cutting off part of the vertebral lateral mass fixation combined with exercise therapy. From March 2004 to April 2008, 27 patients included 19 boys and 8 girls, aging 13-21 years with an average of 15 years underwent selective cervical dorsal root cutting off part of the vertebral lateral mass fixation with exercise therapy. The AXIS 8 holes titanium plate was inserted into the lateral mass of spinous process through guidance of the nerve stimulator, choosed fasciculus of low-threshold nerve dorsal root and cut off its 1.5 cm. After two weeks, training exercise therapy was done in patients. Training will include lying position, turning body, sitting position, crawling, kneeling and standing position, walking and so on. Spastic Bobath inhibiting abnormal pattern was done in the whole process of training. The muscular tension, motor function (GMFM), functional independence (WeeFIM) were observed after treatment. All patients were followed up from 4 to 16 months with an average of 6 months. Muscular tension score were respectively 3.30 +/- 0.47 and 1.25 +/- 0.44 before and after treatment;GMFM score were respectively 107.82 +/- 55.17 and 131.28 +/- 46.45; WeeFIM score were respectively 57.61 +/- 25.51 and 87.91 +/- 22.39. There was significant improvement before and after treatment (P cerebral paralysis of the upper limbs is safe and effective method, which can decrease muscular tension and improve motor function, which deserves more wide use.

  19. Anti-hyperglycemic effect of Psacalium peltatum.

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    Contreras-Weber, Claudia; Perez-Gutierrez, Salud; Alarcon-Aguilar, Francisco; Roman-Ramos, Ruben

    2002-01-01

    The purpose of this research was to study the anti-hyperglycemic effect of Psacalium peltatum, a folk medicinal plant used in treatment of diabetes mellitus. This plant was processed in the traditional way (water decoction) and administered i.p. to normoglycemic and diabetic mice. Hexane, chloroform, methanol and water extracts were administered to fasting healthy mice. The results showed that the water decoction, methanolic extract and aqueous extracts exhibit hypoglycemic activity in the studied mice. The methanolic extract was submitted to a separation process by chromatographic column from which seven fractions were obtained. Each fraction was administered to healthy mice and hypoglycemic activity was found in fraction VII. A second chromatographic separation was performed on this fraction, to yield seven subfractions. The results of the biological trials showed that the subfractions SFII and SFIII significantly reduce blood glucose levels in healthy mice.

  20. CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Nav1.8 sodium channels in dorsal root ganglion neurons

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    Kao Der-Jang

    2012-08-01

    Full Text Available Abstract Background Inflammation or nerve injury-induced upregulation and release of chemokine CC chemokine ligand 2 (CCL2 within the dorsal root ganglion (DRG is believed to enhance the activity of DRG nociceptive neurons and cause hyperalgesia. Transient receptor potential vanilloid receptor 1 (TRPV1 and tetrodotoxin (TTX-resistant Nav1.8 sodium channels play an essential role in regulating the excitability and pain transmission of DRG nociceptive neurons. We therefore tested the hypothesis that CCL2 causes peripheral sensitization of nociceptive DRG neurons by upregulating the function and expression of TRPV1 and Nav1.8 channels. Methods DRG neuronal culture was prepared from 3-week-old Sprague–Dawley rats and incubated with various concentrations of CCL2 for 24 to 36 hours. Whole-cell voltage-clamp recordings were performed to record TRPV1 agonist capsaicin-evoked inward currents or TTX-insensitive Na+ currents from control or CCL2-treated small DRG sensory neurons. The CCL2 effect on the mRNA expression of TRPV1 or Nav1.8 was measured by real-time quantitative RT-PCR assay. Results Pretreatment of CCL2 for 24 to 36 hours dose-dependently (EC50 value = 0.6 ± 0.05 nM increased the density of capsaicin-induced currents in small putative DRG nociceptive neurons. TRPV1 mRNA expression was greatly upregulated in DRG neurons preincubated with 5 nM CCL2. Pretreating small DRG sensory neurons with CCL2 also increased the density of TTX-resistant Na+ currents with a concentration-dependent manner (EC50 value = 0.7 ± 0.06 nM. The Nav1.8 mRNA level was significantly increased in DRG neurons pretreated with CCL2. In contrast, CCL2 preincubation failed to affect the mRNA level of TTX-resistant Nav1.9. In the presence of the specific phosphatidylinositol-3 kinase (PI3K inhibitor LY294002 or Akt inhibitor IV, CCL2 pretreatment failed to increase the current density of capsaicin-evoked inward currents or TTX-insensitive Na+ currents and

  1. Sex differences in pain-related behavior and expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia of rats with diabetes type 1 and type 2.

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    Ferhatovic, Lejla; Banozic, Adriana; Kostic, Sandra; Sapunar, Damir; Puljak, Livia

    2013-06-01

    Sex differences in pain-related behavior and expression of calcium/calmodulin dependent protein kinase II (CaMKII) in dorsal root ganglia were studied in rat models of Diabetes mellitus type 1 (DM1) and type 2 (DM2). DM1 was induced with 55mg/kg streptozotocin, and DM2 with a combination of high-fat diet and 35mg/kg of streptozotocin. Pain-related behavior was analyzed using thermal and mechanical stimuli. The expression of CaMKII was analyzed with immunofluorescence. Sexual dimorphism in glycemia, and expression of CaMKII was observed in the rat model of DM1, but not in DM2 animals. Increased expression of total CaMKII (tCaMKII) in small-diameter dorsal root ganglia neurons, which are associated with nociception, was found only in male DM1 rats. None of the animals showed increased expression of the phosphorylated alpha CaMKII isoform in small-diameter neurons. The expression of gamma and delta isoforms of CaMKII remained unchanged in all analyzed animal groups. Different patterns of glycemia and tCaMKII expression in male and female model of DM1 were not associated with sexual dimorphism in pain-related behavior. The present findings do not suggest sex-related differences in diabetic painful peripheral neuropathy in male and female diabetic rats. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Use of Sodium Bicarbonate in Diabetic Hyperglycemic Emergencies

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    Diana Machado Ramírez

    2013-09-01

    Full Text Available Background: diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic state are two of the major metabolic emergencies that may occur. These conditions are not always treated properly.Objective: to describe the metabolic hyperglycemic emergencies in diabetic patients treated in the Intensive Care Unit, and to assess the use of sodium bicarbonate. Methods: a descriptive, cross-sectional study was conducted including 52 patients admitted to the Intensive Care Unit of the Enrique Cabrera Hospital from 2000 through 2007. The following variables were analyzed: type of diabetes mellitus, type of acute complication, use or not of sodium bicarbonate, blood gases, ionogram and progress of patients. Kitabchi criteria were used for the diagnosis of diabetic ketoacidosis and its severity and for the diagnosis of the hyperglycemic state as well. Criteria proposed by an Expert Committee of the American Diabetes Association and a World Health Organization Expert Committee were adopted for the diagnosis of diabetes and its classification. Results: diabetic ketoacidosis was confirmed in 57,5 % of type 1 diabetic patients and in 42,5 % of those with type 2 diabetes. Hyperosmolar hyperglycemic nonketotic state was observed in 23,0 % of type 2 diabetics. There was not any death among patients with diabetic ketoacidosis who did not use sodium bicarbonate whereas 80,0 % of patients with hyperglycemic state who used it died. Conclusions: diabetic ketoacidosis was the most common complication. Mortality due to ketoacidosis and hyperosmolar hyperglycemic nonketotic state was high. Sodium bicarbonate was not properly used.

  3. The Hepatic Protection Effects of Hepassocin in Hyperglycemic Crisis.

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    Ou, Horng-Yih; Wu, Hung-Tsung; Lin, Ching-Han; Du, Ye-Fong; Hu, Che-Yuan; Hung, Hao-Chang; Wu, Pansee; Li, Hung-Yuan; Wang, Shu-Huei; Chang, Chih-Jen

    2017-07-01

    High glucose generates reactive oxygen species (ROS) and contributes to glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional damage to the liver. However, only a mild hepatic dysfunction was observed in subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic protective effect. Hepassocin is a hepatokine that modulates the proliferation and metabolism of hepatocytes and also exerts protective activity in liver injury. However, its role in hyperglycemic crisis-induced hepatic dysfunction remains unknown. To investigate the possible hepatic protection effects of hepassocin in hyperglycemic crisis. Plasma hepassocin concentrations and routine biochemistry were measured in 21 patients with hyperglycemic crisis before and after standard treatments. The effects of hepassocin on hepatic functions were evaluated in streptozotocin-induced hyperglycemic mice (STZ mice). HepG2 cells were used to clarify the possible mechanisms regulating hepassocin expression. Plasma hepassocin concentrations decreased significantly in subjects with hyperglycemic crisis after standard treatment accompanied by improved hepatic functions. Correction of hyperglycemia in STZ mice also decreased the hepatic hepassocin expression. Injection of recombinant hepassocin improved hepatic functions and histologic changes and increased the expression of antioxidative stress proteins, including superoxide dismutase 1 (SOD1). In HepG2 cells, high glucose increased hepassocin expression through signal transducer and activator of transcription 3 and hepatocyte nuclear factor-related pathways. We also demonstrated that hepassocin increased SOD1 expression through an extracellular signal-regulated kinase 1/2 nuclear factor erythroid-2-related factor 2 pathway, decreasing ethyl acetate-induced ROS production and improving cell viability. Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.

  4. Evaluation of anti-hyperglycemic activity and side effects of ...

    African Journals Online (AJOL)

    In folk medicine, several plants, among which the small centaury, are recommended for the treatment of diabetes type 2 in humans. An experimental study to evaluate anti hyperglycemic effect of Erythraea centaurium (L.) Pers. was performed on wistar rats. Normoglycemic rats and rats subjected to oral glucose tolerance ...

  5. Hyperglycemic Emergency in Pregnancy- Case Report and Review ...

    African Journals Online (AJOL)

    Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two of the most serious acute complications of diabetes. The occurrence of hyperglycaemic emergency in pregnancy compromises both the fetus and the mother and is associated with excess fetal and maternal mortality. It usually occurs in the ...

  6. Hyperglycemic crisis precipitated by Lassa fever in a patient with ...

    African Journals Online (AJOL)

    Hyperglycemic crisis (HC) is an acute complication of diabetes mellitus (DM) that is commonly precipitated by infections and non.compliance with therapy. Viral precipitant of HC is uncommon. To report a rare case of HC unmasked by Lassa fever in a patient previously not known to have diabetes mellitus. A 54 year old lady ...

  7. Dorsal Pancreatic Agenesis

    OpenAIRE

    Oya Uygur-Bayramiçli; Can Dolapçioglu; Derya Öztas; Resat Dabak; Gamze Kiliçoglu

    2007-01-01

    Context Agenesis of the dorsal pancreas is a rare entity and might present with various symptoms. We report a case which presented with chronic pancreatitis. Case report The patient presented with epigastric pain and we found dorsal pancreatic agenesis causing chronic pancreatitis. Conclusions Dorsal pancreatic agenesis can be easily diagnosed with new techniques and its association with clinical syndromes can be better understood.

  8. Bay11-7082 attenuates neuropathic pain via inhibition of nuclear factor-kappa B and nucleotide-binding domain-like receptor protein 3 inflammasome activation in dorsal root ganglions in a rat model of lumbar disc herniation

    Directory of Open Access Journals (Sweden)

    Zhang AL

    2017-02-01

    Full Text Available Ailiang Zhang, Kun Wang, Lianghua Ding, Xinnan Bao, Xuan Wang, Xubin Qiu, Jinbo Liu Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China Abstract: Lumbar disc herniation (LDH is an important cause of radiculopathy, but the underlying mechanisms are incompletely understood. Many studies suggested that local inflammation, rather than mechanical compression, results in radiculopathy induced by LDH. On the molecular and cellular level, nuclear factor-kappa B (NF-κB and nucleotide-binding domain-like receptor protein 3 (NLRP3 inflammasome have been implicated in the regulation of neuroinflammation formation and progression. In this study, the autologous nucleus pulposus (NP was implanted in the left L5 dorsal root ganglion (DRG to mimic LDH in rats. We investigated the expression of NF-κB and the components of NLRP3 inflammasome in the DRG neurons in rats. Western blotting and immunofluorescence for the related molecules, including NLRP3, apoptosis-associated speck-like protein containing caspase-1 activator domain (ASC, caspase-1, interleukin (IL-1β, IL-18, IκBα, p-IκBα, p65, p-p65, and calcitonin gene-related peptide (CGRP were examined. In the NP-treated group, the activations of NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 in DRG neurons in rats were elevated at 1 day after surgery, and the peak occurred at 7 days. Treatment with Bay11-7082, an inhibitor of the actions of IKK-β, was able to inhibit expression and activation of the molecules (NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 and relieve the pain in rats. Our study shows that NF-κB and NLRP3 inflammasome are involved in the maintenance of NP-induced pain, and that Bay11-7082 could alleviate mechanical allodynia and thermal hyperalgesia by inhibiting NF-κB and NLRP3 inflammasome activation. Keywords: pain, NLRP3, NF-κB, dorsal root ganglion, nucleus pulposus

  9. Expression of the sodium channel transcripts Na(v)1.8 and Na(v)1.9 in injured dorsal root ganglion neurons of interferon-gamma or interferon-gamma receptor deficient mice.

    Science.gov (United States)

    Eriksson, Jonas; Fried, Kaj

    2003-03-06

    Changes in the dorsal root ganglion (DRG) expression of the sodium channels Na(v)1.8 and Na(v)1.9 may contribute to injury-induced hyperexcitability and pain. Interferon (IFN)-gamma receptor -/- mice display a reduced pain-related behavior after nerve injury as compared to wild-type mice (NeuroReport 8 (1997) 1311). To elucidate a possible role for IFN-gamma in the regulation of sodium channels, we have studied the DRG mRNA expression of Na(v)1.8/Na(v)1.9 in IFN-gamma- or IFN-gamma receptor-deficient mice. In both types of mice, nerve damage induced a downregulation of Na(v)1.8 as well as Na(v)1.9. The magnitude of this reduction was similar to that observed in wild-type animals. These results indicate that the downregulation of Na(v)1.8/Na(v)1.9 in damaged DRG neurons is not influenced by IFN-gamma. Thus, the reduced pain-related behavior of nerve-injured IFN-gamma receptor null mice is not due to differential changes in the regulation of Na(v)1.8/Na(v)1.9 mRNA.

  10. Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia

    Directory of Open Access Journals (Sweden)

    Chun-Ping Huang

    2013-01-01

    Full Text Available Several voltage-gated sodium channels (Navs from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG. We injected carrageenan and complete Freund's adjuvant (CFA into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36 acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36 acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

  11. Acid activation of Trpv1 leads to an up-regulation of calcitonin gene-related peptide expression in dorsal root ganglion neurons via the CaMK-CREB cascade: a potential mechanism of inflammatory pain.

    Science.gov (United States)

    Nakanishi, Masako; Hata, Kenji; Nagayama, Tomotaka; Sakurai, Teruhisa; Nishisho, Toshihiko; Wakabayashi, Hiroki; Hiraga, Toru; Ebisu, Shigeyuki; Yoneda, Toshiyuki

    2010-08-01

    Increased production of calcitonin gene-related peptide (CGRP) in sensory neurons is implicated in inflammatory pain. The inflammatory site is acidic due to proton release from infiltrating inflammatory cells. Acid activation of peripheral nociceptors relays pain signals to the CNS. Here, we examined whether acid activated the transient receptor potential vanilloid subtype 1 (Trpv1), a widely recognized acid-sensing nociceptor and subsequently increased CGRP expression. Chemically induced inflammation was associated with thermal hyperalgesia and increased CGRP expression in dorsal root ganglion (DRG) in rats. In organ cultures of DRG, acid (pH 5.5) elevated CGRP expression and the selective Trpv1 antagonist 5'-Iodoresiniferatoxin decreased it. Trpv1-deficient DRG showed reduced CGRP increase by acid. Of note, many of CGRP/Trpv1-positive DRG neurons exhibited the phosphorylation of cAMP response element-binding protein (CREB), a nociceptive transcription factor. Knockdown of CREB by small interfering RNA or a dominant-negative form of CREB diminished acid-elevated CGRP expression. Acid elevated the transcriptional activity of CREB, which in turn stimulated CGRP gene promoter activity. These effects were inhibited by a Ca(2+)/calmodulin-dependent protein kinase (CaMK) inhibitor KN-93. In conclusion, our results suggest that inflammatory acidic environments activate Trpv1, leading to an up-regulation of CGRP expression via CaMK-CREB cascade, a series of events that may be associated with inflammatory pain.

  12. Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

    Science.gov (United States)

    Huang, Chun-Ping; Chen, Hsiang-Ni; Su, Hong-Lin; Hsieh, Ching-Liang; Chen, Wei-Hsin; Lai, Zhen-Rung; Lin, Yi-Wen

    2013-01-01

    Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

  13. Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain.

    Science.gov (United States)

    Qiu, Fang; Jiang, Yuge; Zhang, Hong; Liu, Yanhong; Mi, Weidong

    2012-03-23

    In attempt to understand the underlying mechanisms of cancer-induced bone pain, we investigated the presence of two tetrodotoxin-resistant sodium channels, Nav1.8 (SNS/PN3) and Nav1.9 (SNS2/NaN), in dorsal root ganglia (DRG) neurons in an animal model of bone cancer pain. Thirty-six female Sprague-Dawley rats were randomized into three groups: Sham operation group (Sham), cancer-bearing animals killed after 7 days (C7) and cancer-bearing animals killed after 14 days group (C14). After establishment of bone cancer pain model, behavioral tests were carried out to determine the paw withdrawal threshold (PWT) of mechanical and thermal hyperalgesia, respectively. Real-time RT-PCR, Western bolt and Immunofluorescence were used to determine the mRNA and protein expression of Nav1.8 and Nav1.9 in ipsilateral lumbar 4-5 DRG. Compared to Sham group, PWT of mechanical and thermal hyperalgesia in C14 group displayed a significant decrease (PNav1.9 exhibited a significant up-regulation in C14 group (8.9 times and 9 times, respectively, PNav1.9 (PNav1.9 suggested their potential involvement in the development and maintenance of bone cancer pain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Upregulation of the sodium channel NaVβ4 subunit and its contributions to mechanical hypersensitivity and neuronal hyperexcitability in a rat model of radicular pain induced by local dorsal root ganglion inflammation.

    Science.gov (United States)

    Xie, Wenrui; Tan, Zhi-Yong; Barbosa, Cindy; Strong, Judith A; Cummins, Theodore R; Zhang, Jun-Ming

    2016-04-01

    High-frequency spontaneous firing in myelinated sensory neurons plays a key role in initiating pain behaviors in several different models, including the radicular pain model in which the rat lumbar dorsal root ganglia (DRG) are locally inflamed. The sodium channel isoform NaV1.6 contributes to pain behaviors and spontaneous activity in this model. Among all isoforms in adult DRG, NaV1.6 is the main carrier of tetrodotoxin-sensitive resurgent Na currents that allow high-frequency firing. Resurgent currents flow after a depolarization or action potential, as a blocking particle exits the pore. In most neurons, the regulatory β4 subunit is potentially the endogenous blocker. We used in vivo siRNA-mediated knockdown of NaVβ4 to examine its role in the DRG inflammation model. NaVβ4 but not control siRNA almost completely blocked mechanical hypersensitivity induced by DRG inflammation. Microelectrode recordings in isolated whole DRG showed that NaVβ4 siRNA blocked the inflammation-induced increase in spontaneous activity of Aβ neurons and reduced repetitive firing and other measures of excitability. NaVβ4 was preferentially expressed in larger diameter cells; DRG inflammation increased its expression, and this was reversed by NaVβ4 siRNA, based on immunohistochemistry and Western blotting. NaVβ4 siRNA also reduced immunohistochemical NaV1.6 expression. Patch-clamp recordings of tetrodotoxin-sensitive Na currents in acutely cultured medium diameter DRG neurons showed that DRG inflammation increased transient and especially resurgent current, effects blocked by NaVβ4 siRNA. NaVβ4 may represent a more specific target for pain conditions that depend on myelinated neurons expressing NaV1.6.

  15. Differential effect of D623N variant and wild-type Na(v)1.7 sodium channels on resting potential and interspike membrane potential of dorsal root ganglion neurons.

    Science.gov (United States)

    Ahn, Hye-Sook; Vasylyev, Dmytro V; Estacion, Mark; Macala, Lawrence J; Shah, Palak; Faber, Catharina G; Merkies, Ingemar S J; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2013-09-05

    Sodium channel NaV1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic ganglion neurons. Gain-of-function NaV1.7 mutations/variants have been identified in the painful disorders inherited erythromelalgia and small-fiber neuropathy (SFN). DRG neurons transfected with these channel variants display depolarized resting potential, reduced current-threshold, increased firing-frequency and spontaneous firing. Whether the depolarizing shift in resting potential and enhanced spontaneous firing are due to persistent activity of variant channels, or to compensatory changes in other conductance(s) in response to expression of the variant channel, as shown in model systems, has not been studied. We examined the effect of wild-type NaV1.7 and a NaV1.7 mutant channel, D623N, associated with SFN, on resting potential and membrane potential during interspike intervals in DRG neurons. Resting potential in DRG neurons expressing D623N was depolarized compared to neurons expressing WT-NaV1.7. Exposure to TTX hyperpolarized resting potential by 7mV, increased current-threshold, decreased firing-frequency, and reduced NMDG-induced-hyperpolarization in DRG neurons expressing D623N. To assess the contribution of depolarized resting potential to DRG neuron excitability, we mimicked the mutant channel's depolarizing effect by current injection to produce equivalent depolarization; the depolarization decreased current threshold and increased firing-frequency. Voltage-clamp using ramp or repetitive action potentials as commands showed that D623N channels enhance the TTX-sensitive inward current, persistent at subthreshold membrane voltages, as predicted by a Hodgkin-Huxley model. Our results demonstrate that a variant of NaV1.7 associated with painful neuropathy depolarizes resting membrane potential and produces an enhanced inward current during interspike intervals, thereby contributing to DRG neuron hyperexcitability. Copyright © 2013 Elsevier B.V. All rights

  16. Stromal Cell-Derived Factor 1 Increases Tetrodotoxin-Resistant Sodium Currents Nav1.8 and Nav1.9 in Rat Dorsal Root Ganglion Neurons via Different Mechanisms.

    Science.gov (United States)

    Qiu, Fang; Li, Yang; Fu, Qiang; Fan, Yong-Yan; Zhu, Chao; Liu, Yan-Hong; Mi, Wei-Dong

    2016-07-01

    Stromal cell-derived factor 1 (SDF-1)/chemokine CXC motif ligand 12 (CXCL12), a chemokine that is upregulated in dorsal root ganglion (DRG) during chronic pain models, has recently been found to play a central role in pain hypersensitivity. The purpose of present study is to investigate the functional impact of SDF-1 and its receptor, chemokine CXC motif receptor 4 (CXCR4), on two TTXR sodium channels in rat DRG using electrophysiological techniques. Preincubation with SDF-1 caused a concentration-dependent increase of Nav1.8 and Nav1.9 currents amplitudes in acutely isolated small diameter DRG neurons in short-term culture. As to Nav1.9, changes in current density and kinetic properties of Nav1.9 current evoked by SDF-1(50 ng/ml) was eliminated by CXCR4 antagonist AMD3100 and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. The increase in Nav1.9 current was also blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of Gi/o but not Gs subunits. As to Nav1.8, inhibitors (AMD3100, PTX, CTX, LY294002) used in present study didn't inhibit the increased amplitude of Nav1.8 current and shifted activation curve of Nav1.8 in a hyperpolarizing direction in the presence of SDF-1 (50 ng/ml). In conclusion, our data demonstrated that SDF-1 may excite primary nociceptive sensory neurons by acting on the biophysical properties of Nav1.8 and Nav1.9 currents but via different mechanisms.

  17. Inhibition of the TRPM2 and TRPV1 Channels through Hypericum perforatum in Sciatic Nerve Injury-induced Rats Demonstrates their Key Role in Apoptosis and Mitochondrial Oxidative Stress of Sciatic Nerve and Dorsal Root Ganglion

    Directory of Open Access Journals (Sweden)

    Fuat Uslusoy

    2017-05-01

    Full Text Available Sciatic nerve injury (SNI results in neuropathic pain, which is characterized by the excessive Ca2+ entry, reactive oxygen species (ROS and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP. The HP groups received 30 mg/kg HP for 4 weeks after SNI induction. TRPM2 and TRPV1 channels were activated in the neurons by ADP-ribose or cumene peroxide and capsaicin, respectively. The SNI-induced TRPM2 and TRPV1 currents and intracellular free Ca2+ and ROS concentrations were reduced by HP, N-(p-amylcinnamoyl anthranilic acid (ACA, and capsazepine (CapZ. SNI-induced increase in apoptosis and mitochondrial depolarization in sciatic nerve and DRGN of SNI group were decreased by HP, ACA, and CapZ treatments. PARP-1, caspase 3 and 9 expressions in the sciatic nerve, DRGN, skin, and musculus piriformis of SNI group were also attenuated by HP treatment. In conclusion, increase of mitochondrial ROS, apoptosis, and Ca2+ entry through inhibition of TRPM2 and TRPV1 in the sciatic nerve and DRGN neurons were decreased by HP treatment. The results may be relevant to the etiology and treatment of SNI by HP.

  18. Anti-inflammatory effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in neuronal cultures of dorsal root ganglia and myelinating cells of the peripheral nervous system.

    Science.gov (United States)

    Ramesh, Geeta; Meisner, Olivia C; Philipp, Mario T

    2015-12-23

    Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), could result in cognitive impairment, motor dysfunction, and radiculoneuritis. We hypothesized that inflammation is a key factor in LNB pathogenesis and recently evaluated the effects of dexamethasone, a steroidal anti-inflammatory drug, and meloxicam a non-steroidal anti-inflammatory drug (NSAID), in a rhesus monkey model of acute LNB. Dexamethasone treatment significantly reduced the levels of immune mediators, and prevented inflammatory and/or neurodegenerative lesions in the central and peripheral nervous systems, and apoptosis in the dorsal root ganglia (DRG). However, infected animals treated with meloxicam showed levels of inflammatory mediators, inflammatory lesions, and DRG cell apoptosis that were similar to that of the infected animals that were left untreated. To address the differential anti-inflammatory effects of dexamethasone and meloxicam on neuronal and myelinating cells of the peripheral nervous system (PNS), we evaluated the potential of these drugs to alter the levels of Bb-induced inflammatory mediators in rhesus DRG cell cultures and primary human Schwann cells (HSC), using multiplex enzyme-linked immunosorbent assays (ELISA). We also ascertained the ability of these drugs to modulate cell death as induced by live Bb in HSC using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay and the potential of dexamethasone to modulate Bb-induced apoptosis in HSC by the TUNEL assay. Earlier, we reported that dexamethasone significantly reduced Bb-induced immune mediators and apoptosis in rhesus DRG cell cultures. Here, we report that dexamethasone but not meloxicam significantly reduces the levels of several cytokines and chemokines as induced by live Bb, in HSC and DRG cell cultures. Further, meloxicam does not significantly alter Bb-induced cell death in HSC, while dexamethasone protects HSC against Bb-induced cell death. These data

  19. Measuring beta-cell function relative to insulin sensitivity in youth: Does the hyperglycemic clamp suffice?

    Science.gov (United States)

    To compare beta-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcD...

  20. The Impact of Hyperglycemic Emergencies on the Kidney and Liver

    Directory of Open Access Journals (Sweden)

    Feng Bai

    2013-01-01

    Full Text Available Studies on the alterations of liver and kidney function parameters in patients with diabetic ketoacidosis (DKA and diabetic ketosis (DK were limited. Participants with DKA, DK, non-DK, and healthy controls were enrolled in the current study. Parameters of liver and kidney function were measured and evaluated. The patients with DKA had higher levels of plasma glucose, hemoglobin A1c (HbA1c, uric acid, and creatinine but lower levels of transferases and protein compared with the other three groups ( for all. The patients with DK had higher levels of plasma glucose and HbA1c but lower levels of glutamyl transpeptidase and protein compared with the non-DK and control groups (. Prealbumin levels were significantly reduced in the severe DKA patients compared with the mild/moderate DKA patients. Serum prealbumin levels were correlated with albumin levels (, , HCO3 (, , and arterial pH (, in the DKA patients. A diagnostic analysis showed that lower prealbumin levels significantly reflected the presence of hyperglycemic emergencies (. Liver and kidney function parameters deteriorated, especially in DKA. Prealbumin levels can be of value in detecting the presence of hyperglycemic crisis. This clinical trial is registered with ChiCTR-OCH-12003077.

  1. Right dorsal colitis

    National Research Council Canada - National Science Library

    Karcher, L F; Dill, S G; Anderson, W I; King, J M

    1990-01-01

    Moderate to severe ulcerative colitis of the right dorsal colon was diagnosed by necropsy or by exploratory celiotomy and biopsy in 13 horses with a primary clinical complaint of either colic, diarrhea, or weight loss...

  2. Stereological analysis of Ca(2+)/calmodulin-dependent protein kinase II alpha -containing dorsal root ganglion neurons in the rat: colocalization with isolectin Griffonia simplicifolia, calcitonin gene-related peptide, or vanilloid receptor 1.

    Science.gov (United States)

    Carlton, Susan M; Hargett, Gregory L

    2002-06-17

    The enzyme Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is widely distributed in the nervous system. A previous report describes immunostaining for CaMKII alpha in dorsal root ganglion (DRG) neurons. In this study, CaMKII alpha is colocalized in the rat with three putative markers of nociceptive DRG neurons, isolectin Griffonia simplicifolia (I-B4), identifying small-diameter, "peptide-poor" neurons; calcitonin gene-related peptide (CGRP), identifying " peptide-rich" neurons; or the vanilloid receptor 1 (VR1), identifying neurons activated by heat, acid, and capsaicin. Lumbar 4 and 5 DRG sections were labeled using immunofluorescence or lectin binding histochemistry, and percentages of single and double-labeled CaMKIIalpha neurons were determined. Stereological estimates of total neuron number in the L4 DRG were 13,815 +/- 2,798 and in the L5 DRG were 14,111 +/- 4,043. Percentages of single-labeled L4 DRG neurons were 41% +/- 2% CaMKII alpha, 38% +/- 3% I-B4, 44% +/- 3% CGRP, and 32% +/- 6% VR1. Percentages of single-labeled L5 DRG neurons were 44% +/- 5% CaMKII alpha, 48% +/- 2% I-B4, 41% +/- 7% CGRP, and 39% +/- 14% VR1. For L4 and L5, respectively, estimates of double-labeled CaMKII alpha neurons showed 34% +/- 2% and 38% +/- 17% labeled for I-B4, 25% +/- 14% and 19% +/- 10% labeled for CGRP, and 37% +/- 7% and 38% +/- 5% labeled for VR1. Conversely, for L4 and L5, respectively, 39% +/- 14% and 38% +/- 7% I-B4 binding neurons, 24% +/- 12% and 23% +/- 10% CGRP neurons, and 42% +/- 7% and 35% +/- 7% VR1 neurons labeled for CaMKIIalpha. The mean diameter of CaMKII alpha - labeled neurons was approximately 27 microm, confirming that this enzyme was preferentially localized in small DRG neurons. The results indicate that subpopulations of DRG neurons containing CaMKII alpha are likely to be involved in the processing of nociceptive information. Thus, this enzyme may play a critical role in the modulation of nociceptor activity and plasticity of primary

  3. Aggressive Fluid Resuscitation in Severe Pediatric Hyperglycemic Hyperosmolar Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Sharara-Chami Rana

    2010-03-01

    Full Text Available Objective. This report describes a severe case of hyperglycemic hyperosmolar syndrome complicated by rhabdomyolysis, acute kidney injury, hyperthermia, and hypovolemic shock, with management centred upon fluid administration. Design. Case report. Setting. Pediatric intensive care unit in university teaching hospital. Patients. 12 years old adolescent female presenting with hyperglycemic hyperosmolar syndrome with a new diagnosis of type 2 diabetes mellitus. Intervention. Aggressive fluid resuscitation and insulin. Main results. The patient had a good outcome, discharged home on hospital day 6. Conclusions. Hyperglycemic hyperosmolar syndrome is associated with a number of complications. Management strategies are undefined, given the rarity of its presentation, and further studies are warranted.

  4. Aggressive Fluid Resuscitation in Severe Pediatric Hyperglycemic Hyperosmolar Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Srinivas Murthy

    2010-01-01

    Full Text Available Objective. This report describes a severe case of hyperglycemic hyperosmolar syndrome complicated by rhabdomyolysis, acute kidney injury, hyperthermia, and hypovolemic shock, with management centred upon fluid administration. Design. Case report. Setting. Pediatric intensive care unit in university teaching hospital. Patients. 12 years old adolescent female presenting with hyperglycemic hyperosmolar syndrome with a new diagnosis of type 2 diabetes mellitus. Intervention. Aggressive fluid resuscitation and insulin. Main results. The patient had a good outcome, discharged home on hospital day 6. Conclusions. Hyperglycemic hyperosmolar syndrome is associated with a number of complications. Management strategies are undefined, given the rarity of its presentation, and further studies are warranted.

  5. Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats.

    Science.gov (United States)

    Yazğan, Yener; Nazıroğlu, Mustafa

    2017-12-01

    Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca2+ influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca2+ influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats. Forty female rats were divided into five groups: a control group, an OVX group, an OVX+E2 group, an OVX+TMX group, and an OVX+RLX group. The OVX+E2, OVX+TMX, and OVX+RLX groups received E2, TMX, and RLX, respectively, for 14 days after the ovariectomy. E2, ovariectomy-induced TRPA1, TRPM2, and TRPV1 current densities, as well as accumulation of cytosolic free Ca2+ in the neurons, were returned to the control levels by E2, TMX, and RLX treatments. In addition, E2, TMX, and RLX via modulation of TRPM2 and TRPV1 activity reduced ovariectomy-induced mitochondrial membrane depolarization, apoptosis, and cytosolic OFR production. TRPM2, TRPV1, PARP, and caspase-3 and caspase-9 expressions were also decreased in the neurons by the E2, TMX, and RLX treatments. In conclusion, we first reported the molecular effects of E2, TMX, and RLX on TRPA1, TRPM2, and TRPV1 channel activation in the OVX rats. In addition, we observed neuroprotective effects of E2, RLX, and TMX on oxidative and apoptotic injuries of the hippocampus and peripheral pain sensory neurons (DRGs) in the OVX rats. Graphical Abstract Possible molecular pathways of involvement of DEX in cerebral ischemia-induced apoptosis, oxidative stress, and calcium accumulation through TRPA1, TRPM2 and TRPV1 in the hippocampus and DRG neurons of rats. The N domain of the

  6. Diffenreces in mia related factors between hyperglycemic and normoglycemic dialysis patients

    OpenAIRE

    Suzuki, Miho; Masakane, Ikuto; Nakajima, Mika; Seino, Yumiko; YABUKI, KIYOTAKA

    2012-01-01

    It is generally accepted that diabetic dialysis patients have nutritional problems more frequently than non-diabetic patients, which has a close relation to the shortness of their lifetime. We compared the MIA related factors between hyperglycemic and normoglycemic dialysis patients with diabetes.110 diabetic dialysis patients were enrolled in this study and they were divided into the next 2 groups; the hyperglycemic group as GA greater than or equal to 23%, and the normoglycemic group as GA ...

  7. Active cocaine use does not increase the likelihood of hyperglycemic crisis.

    Science.gov (United States)

    Modzelewski, Katherine L; Rybin, Denis V; Weinberg, Janice M; Alexanian, Sara M; McDonnell, Marie E; Steenkamp, Devin W

    2017-09-01

    Hyperglycemic crisis encompasses a group of diabetes emergencies characterized by insulin deficiency with high morbidity and mortality. Cocaine use is increasingly prevalent in the United States and may be associated with increased risk of diabetic ketoacidosis. The objective was to determine if active cocaine use at hospital admission could be considered a risk factor for development of hyperglycemic crisis. A retrospective case-control analysis was performed on 950 inpatients with hyperglycemia at an urban academic hospital. Patients admitted with non-emergent hyperglycemia were compared to patients who met criteria for diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hyperosmolar ketoacidosis (HK), based on the absence or presence of cocaine metabolites on urine toxicology screen. Outcomes included frequency of cocaine use in patients with DKA, HHS, HK, and non-emergent hyperglycemia; phenotypic characteristics of cocaine users vs. non-users with hyperglycemia; phenotypic characteristics of patients with hyperglycemic crisis vs. non-emergent hyperglycemia. 950 patients were admitted with hyperglycemia, 133 of which met criteria for hyperglycemic crisis. There was no significant difference in the frequency of cocaine use in individuals with non-emergent hyperglycemia compared to individuals with hyperglycemic crisis (16.9% vs. 17.2%, p = 0.90). 16.9% of patients with DKA, 16.4% of patients with HHS, and 6.4% of patients with HK were cocaine users. We found no association between active cocaine use at the time of hospital admission and development of hyperglycemic crisis, when compared to non-emergent hyperglycemia. The role of routine screening for cocaine use in patients with hyperglycemic crisis is unclear.

  8. Right dorsal colitis.

    Science.gov (United States)

    Karcher, L F; Dill, S G; Anderson, W I; King, J M

    1990-01-01

    Moderate to severe ulcerative colitis of the right dorsal colon was diagnosed by necropsy or by exploratory celiotomy and biopsy in 13 horses with a primary clinical complaint of either colic, diarrhea, or weight loss. Clinical signs varied from acute fulminating diarrhea (possibly with fever), colic, dehydration, endotoxic shock and death, to a chronic condition manifested by mild intermittent colic up to several months in duration, and weight loss with or without mild diarrhea. In a large percentage of the horses, those affected had been hypovolemic and received nonsteroidal anti-inflammatory drugs (NSAID) or had received inappropriately high doses of phenylbutazone before the onset of illness. Experimental treatment of two horses with high doses of a phenylbutazone oral paste preparation (6 gm once daily for 5 days) and limitation of their water intake to approximately one half of maintenance requirement (for 5 days) resulted in reproduction of ulcerative colitis involving only the right dorsal colon, which was apparent at necropsy examination 11 and 15 days after initiation of drug use. It was concluded that localized ulcerative lesions in the right dorsal colon may be a previously unreported manifestation of toxicity due to the administration of NSAID.

  9. [Changes in the expression of large-conductance calcium-activated potassium channels in dorsal root ganglion neurons after electrical injury in rats' sciatic nerves and its influence on sensory conduction function].

    Science.gov (United States)

    Wang, Guangning; Li, Xueyong; Xu, Xiaoli; Ren, Pan

    2016-06-01

    To study the changes in the expression of large-conductance calcium-activated potassium (BKCa) channels in dorsal root ganglion (DRG) neurons after electrical injury in rats' sciatic nerves and its influence on sensory conduction function. One-hundred and thirty-six adult SD rats were divided into normal control group, sham electrical injury group, and 75, 100, 125 V electrical injury groups according to the random number table, with 8 rats in normal control group and 32 rats in each of the rest 4 groups. Rats in normal control group were routinely fed without any treatment. Blunt dissection of the sciatic nerves of left hind leg of rats was performed in sham electrical injury group, while sciatic nerves of left hind leg of rats in electrical injury groups were electrically injured with corresponding voltage. Eight rats of normal control group fed for one week, and 8 rats from each of the rest four groups on post injury day (PID) 3 and in post injury week (PIW) 1, 2, 3 respectively were collected to detect the paw withdrawal mechanical threshold (PWMT). In addition, rats of 100 V electrical injury group in PIW 1 were collected and intrathecally injected with NS1619 after former PWMT detection, and PWMT was detected per 30 minutes within three hours post injection. The rats in each group at each time point were sacrificed after PWMT detection. The DRG of L4 to L6 segments of spinal cord was sampled to observe the BKCa channels distribution with immunohistochemical staining and to detect the protein and mRNA expressions of BKCa channels with Western blotting and reverse transcription-polymerase chain reaction respectively. Data were processed with one-way analysis of variance, analysis of variance of factorial design, and SNK test. (1) The PWMT values of rats in 75 and 100 V electrical injury groups on PID 3 and in PIW 1, 2, 3 were (5.8±0.6), (5.0±0.8), (4.2±0.3), (5.9±1.1) g; (5.3±1.3), (5.9±2.0), (4.5±2.7), (4.3±1.3) g, respectively, which were

  10. Microvascular Blood Flow Improvement in Hyperglycemic Obese Adult Patients by Hypocaloric Diet.

    Science.gov (United States)

    Mastantuono, T; Di Maro, M; Chiurazzi, M; Battiloro, L; Starita, N; Nasti, G; Lapi, D; Iuppariello, L; Cesarelli, M; D'Addio, G; Colantuoni, A

    2016-11-01

    The present study was aimed to assess the changes in skin microvascular blood flow (SBF) in newly diagnosed hyperglycemic obese subjects, administered with hypocaloric diet. Adult patients were recruited and divided in three groups: NW group (n=54), NG (n=54) and HG (n=54) groups were constituted by normal weight, normoglycemic and hyperglycemic obese subjects, respectively. SBF was measured by laser Doppler perfusion monitoring technique and oscillations in blood flow were analyzed by spectral methods under baseline conditions, at 3 and 6 months of dietary treatment. Under resting conditions, SBF was lower in HG group than in NG and NW ones. Moreover, all subjects showed blood flow oscillations with several frequency components. In particular, hyperglycemic obese patients revealed lower spectral density in myogenic-related component than normoglycemic obese and normal weight ones. Moreover, post-occlusive reactive hyperemia (PORH) was impaired in hyperglycemic obese compared to normoglycemic and normal weigh subjects. After hypocaloric diet, in hyperglycemic obese patients there was an improvement in SBF accompanied by recovery in myogenic-related oscillations and arteriolar responses during PORH. In conclusion, hyperglycemia markedly affected peripheral microvascular function; hypocaloric diet ameliorated tissue blood flow.

  11. Diffenreces in mia related factors between hyperglycemic and normoglycemic dialysis patients

    Directory of Open Access Journals (Sweden)

    Miho Suzuki

    2012-06-01

    Full Text Available It is generally accepted that diabetic dialysis patients have nutritional problems more frequently than non-diabetic patients, which has a close relation to the shortness of their lifetime. We compared the MIA related factors between hyperglycemic and normoglycemic dialysis patients with diabetes.110 diabetic dialysis patients were enrolled in this study and they were divided into the next 2 groups; the hyperglycemic group as GA greater than or equal to 23%, and the normoglycemic group as GA less than 23%. Nutritional status was evaluated by MIS sheet originally established by Kalantar- Zadeh. Nutritional statuses were categorized as Normal, mild malnourished and moderately/severely malnourished based on the total point of MIS. In the normoglycemic group age, dialysis vintage and serum level of CRP were significantly increased as a nutritional category became worsened. On the other hand in the hyperglycemic group there were no significant differences in MIA related factors among the nutritional categories. Various specific issues which might worsen the nutritional status of hyperglycemic dialysis patients were identified. In the normoglycemic patients malnutrition might has progressed in the similar manner of MIA progression observed in non-diabetic dialysis patients. However, in the hyperglycemic patients malnutrition might has progressed by other specific issues and or hyperglycemia itself. The Patients with severe hyperglycemia cannot live long enough to develop MIA syndrome.

  12. Monosynaptic connections between primary afferents and giant neurons in the turtle spinal dorsal horn

    DEFF Research Database (Denmark)

    Fernández, A; Radmilovich, M; Russo, R E

    1996-01-01

    This paper reports the occurrence of monosynaptic connections between dorsal root afferents and a distinct cell type-the giant neuron-deep in the dorsal horn of the turtle spinal cord. Light microscope studies combining Nissl stain and transganglionic HRP-labeling of the primary afferents have re...

  13. Bursting deep dorsal horn neurons

    DEFF Research Database (Denmark)

    Carlsen, Eva Meier; Rasmussen, Rune

    2017-01-01

    In a recent publication, Thaweerattanasinp et al. (J Neurophysiol 116: 1644–1653, 2016) investigated spinal cord injury and firing properties of deep dorsal horn neurons during NMDA or zolmitriptan application by employing electrophysiology in an in vitro spinal cord preparation. Deep dorsal horn...

  14. CcpA Affects Infectivity of Staphylococcus aureus in a Hyperglycemic Environment

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    Markus Bischoff

    2017-05-01

    Full Text Available Many bacteria regulate the expression of virulence factors via carbon catabolite responsive elements. In Gram-positive bacteria, the predominant mediator of carbon catabolite repression is the catabolite control protein A (CcpA. Hyperglycemia is a widespread disorder that predisposes individuals to an array of symptoms and an increased risk of infections. In hyperglycemic individuals, the bacterium Staphylococcus aureus causes serious, life-threatening infections. The importance of CcpA in regulating carbon catabolite repression in S. aureus suggests it may be important for infections in hyperglycemic individuals. To test this suggestion, hyperglycemic non-obese diabetic (NOD; blood glucose level ≥20 mM mice were challenged with the mouse pathogenic S. aureus strain Newman and the isogenic ccpA deletion mutant (MST14, and the effects on infectivity were determined. Diabetic NOD mice challenged with the ccpA deletion mutant enhanced the symptoms of infection in an acute murine pneumonia model relative to the parental strain. Interestingly, when diabetic NOD mice were used in footpad or catheter infection models, infectivity of the ccpA mutant decreased relative to the parental strain. These differences greatly diminished when normoglycemic NOD mice (blood glucose level ≤ 10 mM were used. These data suggest that CcpA is important for infectivity of S. aureus in hyperglycemic individuals.

  15. Neutrophilic dermatosis of dorsal hands

    Directory of Open Access Journals (Sweden)

    S Kaur

    2015-01-01

    Full Text Available Sweet′s syndrome is characterized by erythematous tender nodules and plaques over face and extremities. Fever, leukocytosis with neutrophilia, and a neutrophilic infiltrate in the dermis are characteristic features. Neutrophilic dermatosis of dorsal hands is a rare localized variant of Sweet′s syndrome occurring predominantly over dorsa of hands. Various degrees of vascular damage may be observed on histopathology of these lesions. Both Sweet′s syndrome and its dorsal hand variant have been reported in association with malignancies, inflammatory bowel diseases, and drugs. We report a patient with neutrophilic dermatoses of dorsal hands associated with erythema nodosum. He showed an excellent response to corticosteroids and dapsone.

  16. Uric Acid Is Protective After Cerebral Ischemia/Reperfusion in Hyperglycemic Mice.

    Science.gov (United States)

    Justicia, Carles; Salas-Perdomo, Angélica; Pérez-de-Puig, Isabel; Deddens, Lisette H; van Tilborg, Geralda A F; Castellví, Clara; Dijkhuizen, Rick M; Chamorro, Ángel; Planas, Anna M

    2017-06-01

    Hyperglycemia at stroke onset is associated with poor long-term clinical outcome in numerous studies. Hyperglycemia induces intracellular acidosis, lipid peroxidation, and peroxynitrite production resulting in the generation of oxidative and nitrosative stress in the ischemic tissue. Here, we studied the effects of acute hyperglycemia on in vivo intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil recruitment, and brain damage after ischemia/reperfusion in mice and tested whether the natural antioxidant uric acid was protective. Hyperglycemia was induced by i.p. administration of dextrose 45 min before transient occlusion of the middle cerebral artery. Magnetic resonance imaging (MRI) was performed at 24 h to measure lesion volume. A group of normoglycemic and hyperglycemic mice received an i.v. injection of micron-sized particles of iron oxide (MPIOs), conjugated with either anti-ICAM-1 antibody or control IgG, followed by T2*w MRI. Neutrophil infiltration was studied by immunofluorescence and flow cytometry. A group of hyperglycemic mice received an i.v. infusion of uric acid (16 mg/kg) or the vehicle starting after 45 min of reperfusion. ICAM-1-targeted MPIOs induced significantly larger MRI contrast-enhancing effects in the ischemic brain of hyperglycemic mice, which also showed more infiltrating neutrophils and larger lesions than normoglycemic mice. Uric acid reduced infarct volume in hyperglycemic mice but it did not prevent vascular ICAM-1 upregulation and did not significantly reduce the number of neutrophils in the ischemic brain tissue. In conclusion, hyperglycemia enhances stroke-induced vascular ICAM-1 and neutrophil infiltration and exacerbates the brain lesion. Uric acid reduces the lesion size after ischemia/reperfusion in hyperglycemic mice.

  17. Neutrophilic dermatosis of dorsal hands

    OpenAIRE

    KAUR, S.; Gupta, D.; Garg, B; Sood, N.

    2015-01-01

    Sweet′s syndrome is characterized by erythematous tender nodules and plaques over face and extremities. Fever, leukocytosis with neutrophilia, and a neutrophilic infiltrate in the dermis are characteristic features. Neutrophilic dermatosis of dorsal hands is a rare localized variant of Sweet′s syndrome occurring predominantly over dorsa of hands. Various degrees of vascular damage may be observed on histopathology of these lesions. Both Sweet′s syndrome and its dorsal hand variant have been r...

  18. Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals

    Directory of Open Access Journals (Sweden)

    Wang X

    2014-11-01

    Full Text Available Xi Wang,1 Debra C DuBois,1,2 Siddharth Sukumaran,2 Vivaswath Ayyar,1 William J Jusko,2,3 Richard R Almon1–3 1Department of Biological Sciences, 2Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA; 3New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA Abstract: Both obesity and chronic inflammation are often associated with insulin resistance and type 2 diabetes. The Zucker diabetic fatty (ZDF rat (fa/fa is an obese animal model frequently used in type 2 diabetes research. The current study determines whether chronic administration (from 5 weeks of age through 24 weeks of age of salsalate, a salicylate with anti-inflammatory properties, would be effective in mitigating diabetes disease progression in ZDF rats. Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability. However, even in the non-drug-treated group, not all ZDF rats became diabetic as expected. Therefore, animals were parsed into two groups, regardless of drug treatment: normoglycemic ZDF rats, which maintained blood glucose profiles identical to nondiabetic Zucker lean rats (ZLRs, and hyperglycemic ZDF rats, which exhibited progressive elevation in blood glucose. To ascertain the differences between ZDF rats that became hyperglycemic and those that did not, relevant physiological indices and expression levels of adiponectin, tumor necrosis factor-α, interleukin-6, and glucocorticoid-induced leucine zipper messenger RNAs in adipose tissue were measured at sacrifice. Plasma C-reactive protein concentrations and expression levels of cytokine and glucocorticoid-induced leucine zipper messenger RNAs suggested more prevalent chronic inflammation in hyperglycemic animals. Early elevation of the insulin-sensitizing adipokine, adiponectin, was present in both ZDF groups, with the rate of its age-related decline

  19. Sentinel visits in emergency department patients with diabetes mellitus as a warning sign for hyperglycemic emergencies.

    Science.gov (United States)

    Yan, Justin W; Gushulak, Katherine M; Columbus, Melanie P; Hamelin, Alexandra L; Wells, George A; Stiell, Ian G

    2017-07-25

    Patients with poorly controlled diabetes mellitus may have a sentinel emergency department (ED) visit for a precipitating condition prior to presenting for a hyperglycemic emergency, such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). This study's objective was to describe the epidemiology and outcomes of patients with a sentinel ED visit prior to their hyperglycemic emergency visit. This was a 1-year health records review of patients≥18 years old presenting to one of four tertiary care EDs with a discharge diagnosis of hyperglycemia, DKA, or HHS. Trained research personnel collected data on patient characteristics, management, disposition, and determined whether patients came to the ED within the 14 days prior to their hyperglycemia visit. Descriptive statistics were used to summarize the data. Of 833 visits for hyperglycemia, 142 (17.0%; 95% CI: 14.5% to 19.6%) had a sentinel ED presentation within the preceding 14 days. Mean (SD) age was 50.5 (19.0) years and 54.4% were male; 104 (73.2%) were discharged from this initial visit, and 98/104 (94.2%) were discharged either without their glucose checked or with an elevated blood glucose (>11.0 mmol/L). Of the sentinel visits, 93 (65.5%) were for hyperglycemia and 22 (15.5%) for infection. Upon returning to the ED, 61/142 (43.0%) were admitted for severe hyperglycemia, DKA, or HHS. In this unique ED-based study, diabetic patients with a sentinel ED visit often returned and required subsequent admission for hyperglycemia. Clinicians should be vigilant in checking blood glucose and provide clear discharge instructions for follow-up and glucose management to prevent further hyperglycemic emergencies from occurring.

  20. Bilateral cataract formation via acute spontaneous fracture of the lens following treatment of hyperglycemic hyperosmolar syndrome

    Directory of Open Access Journals (Sweden)

    Yevgeniy V. Sychev

    2017-09-01

    Conclusions and importance: Acute transient cataracts that develop during correction of hyperglycemic hyperosmolar syndrome are thought to result from osmotic lens swelling. In this case report, internal fracture of the lens was produced by mechanical forces generated in the process of lens swelling occurring as a consequence of initial hyperglycemia and its subsequent correction. This case represents a rare ocular complication of hyperglycemia correction, and provides new evidence that mechanical forces can be part of diabetic cataractogenesis.

  1. Vanadium uptake by biomass of Coprinus comatus and their effect on hyperglycemic mice.

    Science.gov (United States)

    Han, Chunchao; Cui, Bo; Wang, Yingzi

    2008-07-01

    The Vanadium uptake by Coprinus comatus and their co-effect on hyperglycemic mice were studied. By fermentation and AAS analysis, the optimal concentration of vanadium in medium was 0.4%, and the content of vanadium accumulated in the mycelia was 3,528.0 microg/g. At the concentration of 0.4%, the vanadium-associated toxicity was reduced, and its anti-diabetic effects were maintained.

  2. Comprehensive Evaluation of Anti-hyperglycemic Activity of Fractionated Momordica charantia Seed Extract in Alloxan-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shailesh Kumar Choudhary

    2012-01-01

    Full Text Available The present study evaluates anti-hyperglycemic activity of fractionated Momordica charantia (bitter gourd seed extracts. Fasting blood glucose levels were evaluated before and after administration of different fractions of the seed extract. Among the three fractions tested, fraction Mc-3 (15 mg/kg b.wt. showed the maximum anti-hyperglycemic activity and reduced blood glucose levels in experimental diabetic rats significantly. The activities of the key regulatory enzymes of glucose metabolism (hexokinase, pyruvate kinase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase were determined in Mc-3-treated diabetic animals. Once-daily administration of the fraction Mc-3 for prolonged period of 18 days to the experimental diabetic animals did not result in any nephrotoxicity or hepatotoxicity as evident from insignificant changes in biochemical parameters indicative of liver and kidney functions. Further fractionation of the fraction Mc-3 by size exclusion chromatography resulted in a fraction, designated Mc-3.2, possessing anti-hyperglycemic activity. The fraction Mc-3.2 showed the presence of a predominant protein band of ~11 kDa on SDS-PAGE. Loss in anti-hyperglycemic activity of the Mc-3.2 upon protease treatment indicates the proteinaceous nature of the anti-hyperglycemic principles. Overall, the results suggest that Momordica charantia seeds contain an effective anti-hyperglycemic protein(s which may find application in treatment of diabetes without evident toxic effects.

  3. Keyhole interlaminar dorsal rhizotomy for spastic diplegia in cerebral palsy.

    Science.gov (United States)

    Sindou, Marc; Georgoulis, George

    2015-07-01

    The efficiency and safety of dorsal rhizotomies for cerebral palsy lie in the accuracy of radicular identification together with selectivity of root sectioning. Two different exposures are currently in use. The first is extended laminotomy/laminectomy from the upper lumbar level to the sacrum, which allows accurate identification of all L2-S2 roots/rootlets. The second is limited laminotomy exposing the conus/cauda equina at the thoracolumbar junction; this less invasive method limits accessibility to the roots. To optimize the accuracy and selectivity while minimizing invasiveness, the authors developed a tailored interlaminar procedure targeting the radicular levels involved in the harmful components of spasticity directly and individually. Six patients with spastic diplegia at different levels of the Gross Motor Functional Classification System were selected. In each patient, two to three interlaminar spaces, preselected according to planning, were enlarged in the "keyhole" fashion, respecting the spinous processes and interspinous ligaments. Ventral root stimulation identified the radicular level. Dorsal root stimulation evaluated its implication in the hyperactive segmental circuits, helping quantify the percentage of rootlets to be cut. There were neither wound-related nor general complications. At 1 year of follow-up, X-ray examination did not reveal kyphosis or instability. In all children, the excess of spasticity was reduced. The Ashworth score decreased from 3.2 on average to 0.6 postoperatively (range: 2-4 to 0-2). Regarding the functional status at 1 year of follow-up for the three ambulatory children, the Gillette ability-to-walk score increased from 3/10 on average to 7.3/10 postoperatively (range: 2-4 to 7-8). For the three non-ambulatory children, abnormal postures, painful contractures and ease of care were much improved. Keyhole interlaminar dorsal rhizotomy (KIDr) offers direct intradural access to each of the ventral/dorsal roots, thus

  4. Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus

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    Hair Pamela S

    2012-03-01

    Full Text Available Abstract Background Diabetic patients are at increased risk for bacterial infections; these studies provide new insight into the role of the host defense complement system in controlling bacterial pathogens in hyperglycemic environments. Methods The interactions of complement C3 with bacteria in elevated glucose were assayed for complement activation to opsonic forms, phagocytosis and bacterial killing. C3 was analyzed in euglycemic and hyperglycemic conditions by mass spectrometry to measure glycation and structural differences. Results Elevated glucose inhibited S. aureus activation of C3 and deposition of C3b and iC3b on the bacterial surface. S. aureus-generated C5a and serum-mediated phagocytosis by neutrophils were both decreased in elevated glucose conditions. Interestingly, elevated glucose increased the binding of unactivated C3 to S. aureus, which was reversible on return to normal glucose concentrations. In a model of polymicrobial infection, S. aureus in elevated glucose conditions depleted C3 from serum resulting in decreased complement-mediated killing of E. coli. To investigate the effect of differing glucose concentration on C3 structure and glycation, purified C3 incubated with varying glucose concentrations was analyzed by mass spectrometry. Glycation was limited to the same three lysine residues in both euglycemic and hyperglycemic conditions over one hour, thus glycation could not account for observed changes between glucose conditions. However, surface labeling of C3 with sulfo-NHS-biotin showed significant changes in the surface availability of seven lysine residues in response to increasing glucose concentrations. These results suggest that the tertiary structure of C3 changes in response to hyperglycemic conditions leading to an altered interaction of C3 with bacterial pathogens. Conclusions These results demonstrate that hyperglycemic conditions inhibit C3-mediated complement effectors important in the immunological

  5. Treatment of Diabetic Ketoacidosis (DKA)/Hyperglycemic Hyperosmolar State (HHS): Novel Advances in the Management of Hyperglycemic Crises (UK Versus USA).

    Science.gov (United States)

    Dhatariya, Ketan K; Vellanki, Priyathama

    2017-05-01

    Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies that cause high morbidity and mortality. Their treatment differs in the UK and USA. This review delineates the differences in diagnosis and treatment between the two countries. Large-scale studies to determine optimal management of DKA and HHS are lacking. The diagnosis of DKA is based on disease severity in the USA, which differs from the UK. The diagnosis of HHS in the USA is based on total rather than effective osmolality. Unlike the USA, the UK has separate guidelines for DKA and HHS. Treatment of DKA and HHS also differs with respect to timing of fluid and insulin initiation. There is considerable overlap but important differences between the UK and USA guidelines for the management of DKA and HHS. Further research needs to be done to delineate a unifying diagnostic and treatment protocol.

  6. Central projections of primary sensory afferents to the spinal dorsal horn in the long-tailed stingray, Himantura fai.

    Science.gov (United States)

    Kitchener, Peter D; Fuller, Jack; Snow, Peter J

    2010-01-01

    The central projections of primary sensory afferents innervating the caudal region of the pectoral fin of the long-tailed stingray (Himantura fai) were labeled by applying the lipophilic carbocyanine dye DiI to the dorsal roots in fixed tissue. These observations were complemented by examination of hemotoxylin and eosin-stained paraffin sections of the dorsal root entry zone, and transmission electron microscopy of the dorsal horn. Transverse sections of the sensory nerve and dorsal root revealed two distinct myelinated axon sizes in the sensory nerve. Although the thick and thin axons do not appear to group together in the sensory nerves and dorsal root, they segregate into a dorsally directed bundle of thin fibers and a more horizontally directed bundle of thick fibers soon after entering the spinal cord. In DiI-labeled horizontal sections, fibers were observed to enter the spinal cord and diverge into rostrally and caudally directed trajectories. Branching varicose axons could be traced in the dorsal horn gray matter in the segment of entry and about half of the adjacent rostral and caudal segments. In transverse and sagittal sections, DiI-labeled afferents were seen to innervate the superficial and, to a lesser extent, deeper laminae of the dorsal horn, but not the ventral horn. Electron microscopy of unlabeled dorsal horn sections revealed a variety of synaptic morphologies including large presynaptic elements (some containing dense-core vesicles) making synaptic contacts with multiple processes in a glomerular arrangement; in this respect, the synaptic ultrastructure is broadly similar to that seen in the dorsal horn of rodents and other mammals. Copyright © 2010 S. Karger AG, Basel.

  7. Hyperglycemic emergencies in Indian patients with diabetes mellitus on pilgrimage to Amarnathji yatra

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    Mohd Ashraf Ganie

    2012-01-01

    Full Text Available Background: Diabetic ketoacidosis (DKA and hyperosmolar hyperglycemic state (HHS represent two distinct metabolic derangements manifested by insulin deficiency and severe hyperglycemia, with estimated mortality rates of 2.5-9%. In patients with type 2 diabetes mellitus (DM controlled by diet or oral agents, DKA does not occur unless there is significant severe stress such as severe sepsis, major surgery, trauma, etc. We observed many such emergencies occurring in pilgrims. Objective: We analyzed the data of 13 patients with DM admitted in our endocrine department with hyperglycemic emergencies during 2 years of the annual pilgrimage (yatra to Amarnathji. Materials and Methods: We reviewed and analyzed the case records of 13 yatris with DM who were referred and admitted in our hospital with hyperglycemic emergencies during the yatra season (July-August of 2006 and 2007. Results: Eleven of 13 had DKA and 1 each had HHS and hypoglycemia. After initial clinical assessment and blood sampling for blood counts, electrolytes, blood gases, urinalysis, chest radiography, and electrocardiography, these cases were managed with standard protocol published by American Diabetes Association (ADA for the management of DKA and HHS. Average blood glucose was 466 mg/dl and nine subjects had moderate to severe ketonuria. All the cases, except one, were in stable condition at the time of discharge. Conclusion: High altitude, strenuous exertion of going uphill, withdrawal of insulin or oral hypoglycemic drugs, starvation, sepsis, and alcohol intake were recorded as predisposing factors. Therefore, there is an immense need for institution of a special health education program to all the yatris before taking the endeavor.

  8. Exendin-4 Protected against Cognitive Dysfunction in Hyperglycemic Mice Receiving an Intrahippocampal Lipopolysaccharide Injection

    Science.gov (United States)

    Liang, Keng-Chen; Jheng, Yu-Syuan; Jhao, Jhih-Jhen; Su, Ming-Tsan; Lee-Chen, Guey-Jen; Hsieh-Li, Hsiu Mei

    2012-01-01

    Background Chronic hyperglycemia-associated inflammation plays critical roles in disease initiation and the progression of diabetic complications, including Alzheimer’s disease (AD). However, the association of chronic hyperglycemia with acute inflammation of the central nervous system in the progression of AD still needs to be elucidated. In addition, recent evidence suggests that Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damage in the brain. Therefore, the neuroprotective effects of the GLP-1R agonist exendin-4 (EX-4) against hyperglycemia/lipopolysaccharides (LPS) damage were also evaluated in this study. Methodology/Principal Findings Ten days after streptozotocin (STZ) or vehicle (sodium citrate) treatment in mice, EX-4 treatment (10 µg/kg/day) was applied to the mice before intrahippocampal CA1 injection of LPS or vehicle (saline) and continued for 28 days. This study examined the molecular alterations in these mice after LPS and EX4 application, respectively. The mouse cognitive function was evaluated during the last 6 days of EX-4 treatment. The results showed that the activation of NF-κB-related inflammatory responses induced cognitive dysfunction in both the hyperglycemic mice and the mice that received acute intrahippocampal LPS injection. Furthermore, acute intrahippocampal LPS injection exacerbated the impairment of spatial learning and memory through a strong decrease in monoaminergic neurons and increases in astrocytes activation and apoptosis in the hyperglycemic mice. However, EX-4 treatment protected against the cognitive dysfunction resulting from hyperglycemia or/and intrahippocampal LPS injection. Conclusions/Significance These findings reveal that both hyperglycemia and intrahippocampal LPS injection induced cognitive dysfunction via activation of NF-κB-related inflammatory responses. However, acute intrahippocampal LPS injection exacerbated the progression of cognitive dysfunction in the hyperglycemic mice via a

  9. Nesfatin-1 improves oxidative skin injury in normoglycemic or hyperglycemic rats.

    Science.gov (United States)

    Solmaz, Ali; Bahadır, Elif; Gülçiçek, Osman B; Yiğitbaş, Hakan; Çelik, Atilla; Karagöz, Ayça; Özsavcı, Derya; Şirvancı, Serap; Yeğen, Berrak Ç

    2016-04-01

    Hyperglycemia is one of the major causes of suppressed angiogenesis and impaired wound healing leading to chronic wounds. Nesfatin-1 a novel peptide was reported to have antioxidant and anti-apoptotic properties. This study is aimed to investigate the potential healing-promoting effects of nesfatin-1 in non-diabetic or diabetic rats with surgical wounds. In male Sprague-Dawley rats, hyperglycemia was induced by intraperitoneal (ip) injection of streptozotocin (55 mg/kg). Under anesthesia, dorsum skin tissues of normoglycemic (n=16) and hyperglycemic rats were excised (2 × 2 cm, full-thickness), while control rats (n=16) had neither hyperglycemia nor wounds. Half of the rats in each group were treated ip with saline, while the others were treated with nesfatin-1 (2 μg/kg/day) for 3 days until they were decapitated. Plasma interleukin-1-beta (IL-1β), transforming growth factor-beta (TGF-β-1), IL-6 levels, and dermal tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) and caspase-3 activity were measured. For histological examination, paraffin sections were stained with hematoxylin-eosin or Masson's trichrome and immunohistochemistry for vascular endothelial growth factor (VEGF) was applied. ANOVA and Student's t-tests were used for statistical analysis. Compared to control rats, skin MPO activity, MDA and caspase-3 levels were increased similarly in saline-treated normo- and hyperglycemic rats. Nesfatin-1 depressed MDA, caspase-3, MPO activity and IL-1β with concomitant elevations in dermal GSH and plasma TGF-β-1 levels. Histopathological examination revealed regeneration of epidermis, regular arrangement of collagen fibers in the dermis and a decrease in VEGF immunoreactivity in the epidermal keratinocytes of nesfatin-1-treated groups. Nesfatin-1 improved surgical wound healing in both normo- and hyperglycemic rats via the suppression of neutrophil recruitment, apoptosis and VEGF activation. Copyright © 2016 Elsevier Inc. All rights

  10. Anti-hyperglycemic property of Hericium erinaceus – A mini review

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    Chaiyavat Chaiyasut

    2017-11-01

    Full Text Available Hericium erinaceus (H. erinaceus is one of the widely used edible mushrooms around the world, primarily in Asian countries. H. erinaceus is used in traditional medicines, and mushroom based foods. The fruiting body and mycelia of H. erinaceus are extracted using the solvents, and several bioactive compounds were identified. Several studies have reported that those bioactive compounds exhibit many health benefits such as hemagglutinating, antimicrobial, immunomodulatory, antitumor, antioxidant, and anti-aging activities, etc. This manuscript consciously updated the information about the composition of H. erinaceus, H. erinaceus based foods, and anti-hyperglycemic property of H. erinaceus.

  11. Anti-hyperglycemic effect and glucose tolerance of guajava (Psidium guajava L.) leaf ethanol extract in diabetic rats

    Science.gov (United States)

    Yanis Musdja, Muhammad; Mahendra, Feizar; Musir, Ahmad

    2017-12-01

    Traditionally guava (Psidium guajava L) leaf is used for treatment of various ailments like diarrhea, wounds, rheumatism, anti-allergy, ant-spasmodic, etc, as folk medicine. The aim of this research is to know the effect of hypoglycemia and glucose tolerance of ethanol extract of guava leaf against male white rat. The guajava leaf was obtained from Balitro Bogor. Preparation of guajava leaf extract was done by cold maceration extraction technique using ethanol 70%. Male albino rats were made into diabetics using the alloxan method. Rats were divided into 6 groups, as a comparative drug for anti-hyperglycemic used glibenclamid and as a comparative drug for glucose tolerance used acarbose. The result of blood glucometer test showed that ethanol extract 70% of guajava leaf had effect as anti-hyperglycemic and glucose tolerance with no significant difference with glibenclamid drug as anti-hyperglycemic and acarbose as glucose tolerance drug.

  12. Experimental evidences of methanolic extraction of Cressa cretica Linn. on alloxan induced hyperglycemic Wistar rats

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    B. Lalitha Kumari

    2016-09-01

    Full Text Available In the present study, the physico-metabolic parameters measured were: serum insulin, serum lipid profile, serum biomarker enzymes and anti-oxidant enzymes, total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol, total proteins, alanine transaminase (ALT, aspartate transaminase (AST, creatinine, insulin assay (RIA, for in vivo anti-oxidant activity of MECC was measured in liver tissue homogenate (LTH by malondialdehyde (MDA, glutathione (GSH, superoxide dismutase (SOD enzymes and histopathological examination of pancreas were also observed. Previously, the methonolic extract of Cressa cretica Linn. effect on alloxan induced hyperglycemic Wistar rats was proved by taking the parameters like body weight, blood glucose, glycogen content in liver and muscle. Oral administration of MECC (200 mg/kg, 400 mg/kg for 28 days exhibited a significant reduction in blood glucose, serum ALT, AST, CR, lipid profile and hepatic MDA levels. The improvement of hepatic enzymes such as GSH, serum TP, HDL, insulin levels were also observed. The results of this work also suggest that MECC may possess anti-hyperglycemic and anti-oxidant property.

  13. Changes in the expression of NaV1.7, NaV1.8 and NaV1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain.

    Science.gov (United States)

    Strickland, Iain T; Martindale, Jo C; Woodhams, Peter L; Reeve, Alison J; Chessell, Iain P; McQueen, Daniel S

    2008-07-01

    Voltage-gated sodium channels play an essential role in regulating the excitability of nociceptive primary afferent neurones. In particular the tetrodotoxin-sensitive (TTX-S) Na(V)1.7 and the tetrodotoxin-resistant (TTX-R) Na(V)1.8 and Na(V)1.9 channels have been suggested to play a role in inflammatory pain. Previous work has revealed acute administration of inflammatory mediators, such as Freund's complete adjuvant (FCA) or carrageenan caused an upregulation in the levels of Na(V)1.7 and Na(V)1.8 protein in DRG (dorsal root ganglia) tissue up to 4 days post-insult. In the present study, the expression of Na(V)1.7, Na(V)1.8 and Na(V)1.9 was examined over a 28 day timecourse during a rat model of FCA-induced chronic inflammatory joint pain. Using the retrograde tracer Fast Blue (FB) and specific Na(V)1.7, Na(V)1.8 and Na(V)1.9 sodium channel antibodies, immunohistochemical staining techniques were used to study sodium channel expression in a distinct population of L3-L5 knee joint afferent DRGs. In the ganglia, counts were made of positively labelled cells in the FB population. The results demonstrate that, following FCA injection, Na(V)1.9 expression is upregulated at days 14, 21 and 28 post-FCA, with Na(V)1.7 and Na(V)1.8 showing increased channel expression at days 14 and 28. These observations are accompanied by a unilateral joint hypersensitivity in the FCA-injected knee indicated by a behavioural shift in weight distribution measured using an incapacitance tester. The increased presence of these channels suggests that Na(V)1.7, Na(V)1.8 and Na(V)1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult.

  14. Liposarcome dorsal: aspect clinique rare

    Science.gov (United States)

    Agbessi, Odry; Arrob, Adil; Fiqhi, Kamal; Khalfi, Lahcen; Nassih, Mohammed; El Khatib, Karim

    2015-01-01

    Décrit la première fois par Virchow en 1860, le liposarcome est une tumeur mésenchymateuse rare. Cette rareté est relative car les liposarcomes représentent quand même 14 à 18% de l'ensemble des tumeurs malignes des parties molles et ils constituent le plus fréquent des sarcomes des parties molles. Pour la majorité des auteurs, il ne se développerait jamais sur un lipome ou une lipomatose préexistant. Nous rapportons un cas de volumineux liposarcome de la face dorsale du tronc. L'histoire de la maladie, l'aspect clinique inhabituel « de tumeur dans tumeur », l'aspect de la pièce opératoire nous fait évoquer la possibilité de la transformation maligne d'un lipome bénin préexistant. PMID:26113914

  15. Prediction of seizure control in non-ketotic hyperglycemic induced seizures

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    Pratipanawatr Thongchai

    2009-12-01

    Full Text Available Abstract Background To study the factors predictive for seizure control in non-ketotic hyperglycemic induced seizures (NKHS. Methods We studied 21 patients who were clinically diagnosed as NKHS at Khon Kaen University hospital, Thailand. Multiple linear regression analysis was used to identify the factors predictive for seizure control. Results Most patients had no previous history of diabetes and presented with repetitive partial seizures. The mean number of seizure attacks was 45 times prior to admission. The average duration to terminate seizure was 36 hours and significantly predicted by frequency of seizures (estimate 0.9, p value 0.013. Conclusion Frequency of seizures is the only predictive factor for the success of seizure control in NKHS.

  16. A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic Hyperosmolar Nonketotic Syndrome

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    Christina E. Brzezniak

    2017-04-01

    Full Text Available Carcinoid tumors are neuroendocrine tumors that mainly arise in the gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been associated with Cushing syndrome, which results from ectopic adrenocorticotrophic hormone (ACTH secretion. We report the case of a 65-year-old man, a colonel in the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a clinical trial who was hospitalized for complaints of increasing thirst, polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS. Additional findings, which included hypokalemia, hypernatremia, hypertension, metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a fluid replacement and insulin drip resulted in immediate symptomatic improvement. Cushing syndrome should be considered in carcinoid patients with physical stigmata such as moon facies and striae. HHNS may be the presenting clinical feature in patients with impaired glucose metabolism.

  17. Central Diabetes Insipidus and Hyperglycemic Hyperosmolar State Following Accidental Carbon Monoxide Poisoning.

    Science.gov (United States)

    Ul Abideen, Zain; Mahmud, Syed Nayer; Rasheed, Amna; Farooq Qasim, Yusaf; Ali, Furqan

    2017-06-03

    Carbon monoxide poisoning is common and carries significant morbidity and mortality. The nervous system, particularly the brain, is frequently affected by it, owing to its high metabolic activity and oxygen requirements. Carbon monoxide damages the nervous system by both hypoxic and inflammatory mechanisms. Central diabetes insipidus is an extremely rare complication of carbon monoxide poisoning. Herein, we report the case of a young lady, who developed this complication and severe hypernatremia after accidental carbon monoxide poisoning. She also developed a hyperglycemic hyperosmolar state during the treatment for hypernatremia. To the best of our knowledge, both these entities have not been reported together in association with carbon monoxide poisoning. The purpose of this article is to emphasize the anticipation and early recognition of central diabetes insipidus in carbon monoxide poisoning. This can prevent severe hypernatremia and complications associated with its presence and treatment.

  18. Mechanism of anti-hyperglycemic action of Vatairea macrocarpa (Leguminosae): investigation in peripheral tissues.

    Science.gov (United States)

    Baviloni, Paula Domingues; dos Santos, Maísa Pavani; Aiko, Gustavo Mitsuo; Reis, Silvia Regina de Lima; Latorraca, Márcia Queiroz; da Silva, Virginia Claudia; Dall'Oglio, Evandro Luiz; de Sousa, Paulo Teixeira; Lopes, Carbene França; Baviera, Amanda Martins; Kawashita, Nair Honda

    2010-08-19

    Previous studies in our laboratory have demonstrated that the treatment of diabetic rats during 21 days with V. macrocarpa stem-bark ethanolic extract (VmE), reduced glycemia, urinary glucose and urea, increased liver glycogen content and improved other parameters diabetes related. The objective of this study was to evaluate if the anti-hyperglycemic mechanisms of VmE could be caused by improvement in the insulin signaling pathway in the peripheral tissues (liver, adipose and skeletal muscle). Streptozotocin-diabetic rats were separated into two groups: diabetic control (DC) and diabetic treated with VmE (DT) during 21 days. The alterations on the insulin signaling in liver, retroperitoneal adipose tissue (RET) and extensor digitorum longus (EDL) muscles were investigated through determination of insulin receptor (IR), protein kinase B/AKT content and AKT phosphorylation levels using Western blotting analysis. This same methodology was used to evaluate the phosphoenolpyruvate carboxykinase (PEPCK) levels in the liver from these animals. The treatment with the extract increased the content of IR and the basal phosphorylation of AKT in the three tissues. In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced. Data from this work suggest that the anti-hyperglycemic activity of stem-bark extract of V. macrocarpa can occur through stimulation of insulin signaling pathways in peripheral tissues from diabetic rats, mainly in liver and adipose tissue, probably promoting increase in the glucose uptake and liver glycogen synthesis. The concomitant decreasing in hepatic PEPCK levels could be associated to inhibition of gluconeogenesis, which can also contribute to glycemia reduction. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  19. MicroRNA-126 suppresses inflammation in endothelial cells under hyperglycemic condition by targeting HMGB1.

    Science.gov (United States)

    Tang, Song-Tao; Wang, Feng; Shao, Min; Wang, Yuan; Zhu, Hua-Qing

    2017-01-01

    MicroRNA-126(miR-126) targets involved in inflammation need to be identified. In this study, we aim to investigate whether high-mobility group box 1(HMGB1), an inflammation-related gene, is the target of miR-126 in diabetic vascular endothelium. The diabetic apoE -/- mice model, a classical diabetic atherosclerosis model, was established. The aorta of diabetic apoE -/- mice showed decrease of miR-126 and elevation of HMGB1 and inflammation. Next, we employed several in vitro experiments to address the role of miRNA-126 on the regulation of HMGB1 in endothelial cells under hyperglycemic and inflammatory conditions. Manipulation of miRNA levels in human umbilical vein endothelial cells (HUVECs) was achieved by transfecting cells with miR-126 mimic and antagomir. Overexpression of miR-126 could decrease the expression of downstream components of HMGB1 including TNF-α, ROS, and NADPH oxidase activity in HUVECs under hyperglycemic condition. Nevertheless, such phenomenon was completely reversed by miR-126 antagomir. The expression of HMGB1 protein rather than HMGB1 mRNA was down-regulated after transfection with miR-126 mimic, which indicated the modulation of HMGB1 mediated by miR-126 was at the posttranslational level. Luciferase reporter assay confirmed the 3'-UTR of HMGB1 gene was a direct target of miR-126. Western blot analysis also indicated that overexpression of miR-126 contributed to the elevation of p-eNOS, eNOS and p-AKT expressions, respectively. In summary, our findings suggest that miR-126 may suppress inflammation and ROS production in endothelial cells treated by high glucose through modulating the expression of HMGB1. Our study provides a novel pathogenic link between dysregulated miRNA expression and inflammation in diabetic vascular endothelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Anti-oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice

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    Eom SooHyun

    2010-07-01

    Full Text Available Abstract Background Oxidative stress is imperative for its morbidity towards diabetic complications, where abnormal metabolic milieu as a result of hyperglycemia, leads to the onset of several complications. A biological antioxidant capable of inhibiting oxidative stress mediated diabetic progressions; during hyperglycemia is still the need of the era. The current study was performed to study the effect of biologically synthesized gold nanoparticles (AuNPs to control the hyperglycemic conditions in streptozotocin induced diabetic mice. Results The profound control of AuNPs over the anti oxidant enzymes such as GSH, SOD, Catalase and GPx in diabetic mice to normal, by inhibition of lipid peroxidation and ROS generation during hyperglycemia evidence their anti-oxidant effect during hyperglycemia. The AuNPs exhibited an insistent control over the blood glucose level, lipids and serum biochemical profiles in diabetic mice near to the control mice provokes their effective role in controlling and increasing the organ functions for better utilization of blood glucose. Histopathological and hematological studies revealed the non-toxic and protective effect of the gold nanoparticles over the vital organs when administered at dosage of 2.5 mg/kilogram.body.weight/day. ICP-MS analysis revealed the biodistribution of gold nanoparticles in the vital organs showing accumulation of AuNPs in the spleen comparatively greater than other organs. Conclusion The results obtained disclose the effectual role of AuNPs as an anti-oxidative agent, by inhibiting the formation of ROS, scavenging free radicals; thus increasing the anti-oxidant defense enzymes and creating a sustained control over hyperglycemic conditions which consequently evoke the potential of AuNPs as an economic therapeutic remedy in diabetic treatments and its complications.

  1. Effect of intensive insulin treatment on the liver in hyperglycemic rats with liver injury

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    Jun-xun MA

    2014-01-01

    Full Text Available Objective To reproduce a liver injury model in hyperglycemic rats, and investigate the effect of intensive insulin therapy on the liver. Methods Streptozotocin (STZ and D-gal were injected to reproduce hyperglycemic liver injury model in rats. These rats were divided into intensive insulin group (with blood glucose controlled at 6-8mmol/L and conventional treatment group (with blood glucose 9-12mmol/L. Before and 1, 3, 5, 7 days after the reproduction of the model, the rats were sacrificed, and alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, total protein, alkaline phosphatase were determined. The pathological sections of the liver tissues from the model rats and normal rats were made, they were examined after HE staining. Electron microscopic examination was also performed for the liver tissue of the 7-d models. Results Liver injury model of rats with hyperglycemia was successfully reproduced. Intensive insulin therapy can reduce the death risk in model rats. The mortality of rats was lower in intensive insulin group than in conventional treatment group (P<0.01. After intensive insulin therapy, ALT, AST, T-Bil and ALP decreased, while albumin and total protein increased (P<0.01 or P<0.05. HE staining and transmission electron microscopy revealed that degeneration and necrosis of hepatocytes were ameliorated. Conclusion The liver injury model of rats with hyperglycemia has been successfully reproduced. Intensive insulin therapy can decrease the mortality of model rats and reduce the degree of rat liver injury, and the results show a prospect for clinical application. DOI: 10.11855/j.issn.0577-7402.2013.01

  2. Bordetella pertussis-induced Alteration of the Normal Hyperglycemic Response of Mice to 3′,5′-Adenosine Phosphate

    Science.gov (United States)

    Cronholm, Lois S.; Fishel, Charles W.

    1968-01-01

    Blockade of the adrenergic receptors or the injection of Bordetella pertussis vaccine prevented the normal hyperglycemic response of CFW mice to exogenous cyclic 3′,5′-adenosine phosphate (3′,5′-AMP). The cyclic nucleotide was also ineffective in offsetting the histamine hypersensitivity of the β-adrenergically blocked and the pertussis-sensitized groups. These observations suggest that the autonomic malfunction occurs at a point(s) subsequent to release of 3′,5′-AMP. Neither the hyperglycemic effect of epinephrine or 3′,5′-AMP, or both, nor the histamine sensitivity of pertussis-pretreated animals was influenced by the subcutaneous administration of theophylline. PMID:4299372

  3. The morphology and clinical significance of the dorsal meningovertebra ligaments in the cervical epidural space.

    Science.gov (United States)

    Shi, Benchao; Zheng, Xuefeng; Min, Shaoxiong; Zhou, Zhilai; Ding, Zihai; Jin, Anmin

    2014-11-01

    The dural sac is anchored within the vertebral canal by connective tissue called meningovertebral ligaments in the epidural space. During flavectomy and laminectomy, inadvertent disruption of the dorsal meningovertebral ligaments may lead to dura laceration and cerebrospinal fluid (CSF) leaks. All the described dorsal meningovertebral ligaments were located in the lumbar region. A rare study is available about dorsal meningovertebral ligaments of the cervical spinal dura to the adjacent vertebrae. To identify and describe the dorsal meningovertebral ligaments at each cervical level and discuss their clinical significance. A dissection-based study of 22 embalmed cadavers. The anatomy was studied in 22 whole cervical cadavers (11 females, 11 males), prepared with formaldehyde, whose ages at the time of death ranged from 55 to 78 years. The vertebral canal was divided to expose the dural sac and the spinal nerve roots. At all levels of the cervical vertebra, the morphology, quantity, origin, insertion, and spatial orientation of the dorsal meningovertebral ligaments were determined and the length, width or diameter, and thickness of the ligaments were measured with vernier calipers. The dorsal meningovertebral ligaments in the cervical region anchored the posterior dural sac to the ligamentum flavum or laminae. The number of attachment points on the ligamentum flavum was relatively larger than that on the lamina, and the occurrence rate of dorsal meningovertebral ligaments was 100% at C1-C2 and C4--C5. The thickest ligaments were observed at the C1 and C2 vertebrae. The length of the ligaments varied from 1.50 to 35.22 mm, and the orientation of the ligaments mostly was craniocaudal. The morphology of the dorsal meningovertebral ligaments was divided into four types: strip type, cord type, grid type, and thin slice type. In the cervical spine, the dorsal meningovertebral ligaments exist between the posterior dural sac and the ligamentum flavum or lamina. The dorsal

  4. Root hairs

    NARCIS (Netherlands)

    Grierson, C.; Nielsen, E.; Ketelaar, T.; Schiefelbein, J.

    2014-01-01

    Roots hairs are cylindrical extensions of root epidermal cells that are important for acquisition of nutrients, microbe interactions, and plant anchorage. The molecular mechanisms involved in the specification, differentiation, and physiology of root hairs in Arabidopsis are reviewed here. Root hair

  5. Association Of Sleep Deprivation With Reduction In Insulin Sensitivity As Assessed By The Hyperglycemic Clamp Technique In Adolescents

    OpenAIRE

    Rodrigues; AMD; da Silva; CD; Vasques; ACJ; Camilo; DF; Barreiro; Cassani, F; RSL; Zambon; MP; Antonio; MARDM; Geloneze; B.,

    2016-01-01

    IMPORTANCE The association between short sleep duration and decreased insulin sensitivity in adolescents has been described. However, to our knowledge, no studies have investigated this association measuring insulin sensitivity by the hyperglycemic clamp technique. OBJECTIVES To compare the distributions of parameters of insulin resistance in adolescents with sleep deprivation vs adequate sleep, and to investigate the association between sleep deprivation and insulin sensitivity. DESIGN, SETT...

  6. Hyperglycemic condition during puberty increases collagen fibers deposition in the prostatic stroma and reduces MMP-2 activity.

    Science.gov (United States)

    Santos, Sérgio Alexandre Alcantara Dos; Porto Amorim, Elaine Manoela; Ribeiro, Larissa Mayume; Rinaldi, Jaqueline Carvalho; Delella, Flávia Karina; Justulin, Luis Antonio; Felisbino, Sérgio Luis

    2017-12-02

    Puberty is an important period for the growth and maturation of the male reproductive system, and is also a critical window for endocrine or environmental interference. The physiological levels of circulating insulin and hyperglycemic control are important factors for a normal prostate growth. Hyperglycemia during puberty is reported to retard the growth of the prostate gland, with remarkable effects on the epithelial compartment. Here, we investigated the impact of hyperglycemia along with a simultaneous or late insulin replacement on the ventral prostate growth in rats during puberty, paying special attention to the deposition of collagen fibers and activities of gelatinase, matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Hyperglycemia was induced by streptozotocin (STZ) administration in 40-day-old male Wistar rats. A subset of hyperglycemic rats underwent an early insulin replacement (three days after the STZ administration), and another subset underwent a late insulin replacement (twenty days after the STZ administration). Animals were euthanized at 60 and/or 80 days of age. The ventral prostatic lobe was processed for picrosirius red staining, type I and III collagen immunohistochemistry, and gelatin zymography. Hyperglycemic animals showed an increased area of collagen fibers in the prostate, which was composed both types of collagens. MMP-2 activity was significantly reduced in the hyperglycemic animals, while MMP-9 activity was very low and showed no alteration. The simultaneous and late insulin administration restored collagen content and MMP-2 activity. In conclusion, puberty is a critical window for prostate maturation and type-1 diabetes-induced hyperglycemia affects the ratio of the prostatic parenchymal and stromal growth, leading to fibrotic tissues by also MMP-2 down regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The influence of snakehead (Channa striata) fish extract to increase hyperglycemic mice fertility based on spermatogenic cell composition

    Science.gov (United States)

    Hidayati, Dewi; Abdulgani, Nurlita; Ashuri, Nova Maulidina; Sa'adah, Noor Nailis; Lukitasari, Maharani

    2017-06-01

    Reproductive dysfunction is recognized as a consequence of diabetes mellitus. Previous study revealed that snakehead (Channa striata) fish extract can repairing the pancreas histological structure which by that decreasing the blood glucose levels. Further research was conducted to determine the influence of snakehead fish extract (SHFE) to increasing the fertility of hyperglycemic mice based on spermatogenic cell composition. Twenty five adult mice (Mus musculus) were induced intraperitoneally to be hyperglycemic using alloxan monohydrate single dose of 190 mg/kg body weight. Hyperglycemic mice treated orally for 14 days using SHFE which grouped into five treatment dosages. Testicular histology were prepared using the paraffin methods and stained with Haematoxylin and Eosin. According to ANOVA and Tukey's test, it was found that spermatogenic cells population as well as its composition in the testis of mice that treated with SHFE are significantly higher than hyperglichemic mice. The highest dose of SHFE (0.15 ml/day), showed highest spermatogenic cell. All hyperglichemic mice that treated with SHFE exhibited the ratio composition of spermatogonia: spermatocytes: spermatids as same as with control (healthy mice) i.e. 1:1:3 respectively.

  8. The potential of sanrego (Lunasia amara) in enhancing fertility and anti-hyperglycemic effect in diabetic induced male rats

    Science.gov (United States)

    Nor Raidah, R.; Mahanem M., N.; Mohd Shazrul Fazry, S.

    2014-09-01

    Study on the effects of Lunasia amara (LA) aqueous extract on male fertility and its anti-hyperglycemic activity was carried out. Twelve adult male Sprague-Dawley rats were divided into two groups for fertility test; control given orally distilled water (n=6) and treatment (n=6) given 60 mg/kg aqueous extract of LA for 42 days. On day 43, all rats were sacrificed and cauda epididymis was isolated for sperm quality analysis that includes parameter of sperm count, motility and viability. Anti-hyperglycemic study was done on five groups of male rats; I-normal control, II-Diabetic control and three other groups induced diabetic given 500 mg/kg metformin, 60 mg/kg LA and 120 mg/kg LA respectively. Diabetes was induced in the male rats by intravenous injection of 55 mg/kg streptozotocin. On day 7, the fasting blood glucose level was measured from blood drawn by tail snip. Results showed that aqueous extract of LA increased significantly (p diabetic rats by 49.53 %. In conclusion, the aqueous extract of LA effective in increasing sperm quality of male rats and suggest that LA may possess anti-hyperglycemic property.

  9. Anti-Hyperglycemic Properties of Crude Extract and Triterpenes from Poria cocos

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    Tzu-Hsuan Li

    2011-01-01

    Full Text Available Poria cocos, Bai Fu Ling in Chinese, is used in traditional Chinese medicine to treat diabetes. However, its claimed benefits and mechanism are not fully understood. This study aimed to investigate the effect and action of P. cocos on type 2 diabetes. We first performed phytochemical analysis on the crude extract and factions of P. cocos. P. cocos crude extract at 50 mg/kg body weight or more significantly decreased blood glucose levels in db/db mice. Based on a bioactivity-directed fractionation and isolation (BDFI strategy, chloroform fraction and subfractions 4 and 6 of the P. cocos crude extract possessed a blood glucose-lowering effect. Dehydrotumulosic acid, dehydrotrametenolic acid, and pachymic acid were identified from the chloroform sub-fractions 4, 3, and 2, respectively. Dehydrotumulosic acid had anti-hyperglycemic effect to a greater extent than dehydrotrametenolic acid and pachymic acid. Mechanistic study on streptozocin- (STZ- treated mice showed that the crude extract, dehydrotumulosic acid, dehydrotrametenolic acid, and pachymic acid of P. cocos exhibited different levels of insulin sensitizer activity. However, the P. cocos crude extract and triterpenes appeared not to activate PPAR-γ pathway. Overall, the data suggest that the P. cocos extract and its triterpenes reduce postprandial blood glucose levels in db/db mice via enhanced insulin sensitivity irrespective of PPAR-γ.

  10. Anti-hyperglycemic and anti-hyperlipidemic effects of guava leaf extract

    Science.gov (United States)

    2010-01-01

    Psidium guajava Linn. (guava) is used not only as food but also as folk medicine in subtropical areas around the world because of its pharmacologic activities. In particular, the leaf extract of guava has traditionally been used for the treatment of diabetes in East Asia and other countries. Moreover, the anti-hyperglycemic activity of the extract has been reported in some animal models. However, little is known regarding the therapeutic activity of the extract in human clinical trials as well as its underlying therapeutic mechanisms and safety. In Japan, Guava Leaf Tea (Bansoureicha®, Yakult Honsha, Tokyo, Japan) containing the aqueous leaf extract from guava has been approved as one of the Foods for Specified Health Uses and is now commercially available. This review describes the active component of the aqueous guava leaf extract and its inhibition of alpha-glucosidase enzymes in vitro, safety of the extract and Guava Leaf Tea, reduction of postprandial blood glucose elevation, and improvement of hyperglycemia, hyperinsulinemia, hypoadiponectinemia, hypertriglycemia and hypercholesterolemia in murine models and several clinical trials. It is suggested that the chronic suppression of postprandial blood glucose elevation is important in preventing type 2 diabetes mellitus, and that Guava Leaf Tea is considered useful as an alimentotherapy for chronic treatment. PMID:20181067

  11. Anti-hyperglycemic and antigenotoxic potential of Ulva rigida ethanolic extract in the experimental diabetes mellitus.

    Science.gov (United States)

    Celikler, Serap; Tas, Sibel; Vatan, Ozgur; Ziyanok-Ayvalik, Sedef; Yildiz, Gamze; Bilaloglu, Rahmi

    2009-08-01

    An increased reactive oxygen species (ROS) and insufficient antioxidant activity is known in diabetes mellitus (DM). Antioxidant compounds in the human foods or supplementary diets can be used to counteract several diseases. The analysis of micronuclei (MN) is a cytogenetic technique used to show chromosomal damage caused by clastogenic affects. The present study was designed to evaluate: (i) the effects of diabetes mellitus on bone marrow MN frequency, (ii) the effect of oral administration of Ulva rigida ethanolic extract (URE) on MN frequency produced by DM, and (iii) some hematological values in normal and streptozotocin-induced diabetic rats. Daily fluid and food consumptions, weekly body weights, blood glucose concentrations and serum insulin levels were also examined in the study groups during the two different administration periods. The blood glucose concentration and MN frequency have been significantly increased in diabetic rats compared with the normal rats (prigida in vivo. Our results suggest that URE shows strong anti-hyperglycemic and antigenotoxic effect on the genotoxicity produced by DM in rats.

  12. Evaluation of hypoglycemic and anti-hyperglycemic potential of Tridax procumbens (Linn.

    Directory of Open Access Journals (Sweden)

    Jain Kusum

    2009-11-01

    Full Text Available Abstract Background Diabetes is a metabolic disorder affecting carbohydrate, fat and protein metabolism. Tridax procumbens Linn. (Family-Asteraceae; common name-Dhaman grass is common herb found in India. Traditionally, the tribal inhabitants of Udaipur district in Rajasthan (India uses the leaf powder (along with other herb orally to treat diabetes. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's application in traditional medicine system. Methods Extraction of whole plant of T. procumbens using 50%methanol. The extract was tested for acute and sub-chronic anti-hyperglycemic activity in alloxan induced diabetic rats and for acute toxicity test among normal rats. Observations on body weight as well as on the oral glucose tolerance levels were also recorded. Results Oral administration of acute and sub chronic doses (250 and 500 mg/kg b.wt. of T. procumbens extract showed a significant (p T. procumbens were compared with the reference standard drug Glibenclamide (10 mg/kg b.wt.. Conclusion These test results support traditional medicinal use of, T. procumbens for the treatment of diabetes mellitus with corrections in body weight and oral glucose tolerance and no visible signs or symptoms of toxicity in normal rats indicating a high margin of safety. These results warrant follow-up through bioassay-directed isolation of the active principles.

  13. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

    Directory of Open Access Journals (Sweden)

    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  14. The issue of ventral versus dorsal approach in bulbar urethral ...

    African Journals Online (AJOL)

    E. Palminteri

    increased over time the use of Ventral Graft and decreased the use of dorsal graft [7]. From surgical point of view, the Barbagli Dorsal Grafting by Dor- sal approach ... seems reduce the risk of fistula; in reality there is a similar rate of fistula with both ventral and dorsal grafting. The disadvantage of the dorsal approach is that it ...

  15. Functional Assessment of Residues in the Amino- and Carboxyl-Termini of Crustacean Hyperglycemic Hormone (CHH) in the Mud Crab Scylla olivacea Using Point-Mutated Peptides.

    Science.gov (United States)

    Liu, Chun-Jing; Huang, Shiau-Shan; Toullec, Jean-Yves; Chang, Cheng-Yen; Chen, Yun-Ru; Huang, Wen-San; Lee, Chi-Ying

    2015-01-01

    To assess functional importance of the residues in the amino- and carboxyl-termini of crustacean hyperglycemic hormone in the mud crab Scylla olivacea (Sco-CHH), both wild-type and point-mutated CHH peptides were produced with an amidated C-terminal end. Spectral analyses of circular dichroism, chromatographic retention time, and mass spectrometric analysis of the recombinant peptides indicate that they were close in conformation to native CHH and were produced with the intended substitutions. The recombinant peptides were subsequently used for an in vivo hyperglycemic assay. Two mutants (R13A and I69A rSco-CHH) completely lacked hyperglycemic activity, with temporal profiles similar to that of vehicle control. Temporal profiles of hyperglycemic responses elicited by 4 mutants (I2A, F3A, D12A, and D60A Sco-CHH) were different from that elicited by wild-type Sco-CHH; I2A was unique in that it exhibited significantly higher hyperglycemic activity, whereas the remaining 3 mutants showed lower activity. Four mutants (D4A, Q51A, E54A, and V72A rSco-CHH) elicited hyperglycemic responses with temporal profiles similar to those evoked by wild-type Sco-CHH. In contrast, the glycine-extended version of V72A rSco-CHH (V72A rSco-CHH-Gly) completely lost hyperglycemic activity. By comparing our study with previous ones of ion-transport peptide (ITP) and molt-inhibiting hormone (MIH) using deleted or point-mutated mutants, detail discussion is made regarding functionally important residues that are shared by both CHH and ITP (members of Group I of the CHH family), and those that discriminate CHH from ITP, and Group-I from Group-II peptides. Conclusions summarized in the present study provide insights into understanding of how functional diversification occurred within a peptide family of multifunctional members.

  16. Functional Assessment of Residues in the Amino- and Carboxyl-Termini of Crustacean Hyperglycemic Hormone (CHH in the Mud Crab Scylla olivacea Using Point-Mutated Peptides.

    Directory of Open Access Journals (Sweden)

    Chun-Jing Liu

    Full Text Available To assess functional importance of the residues in the amino- and carboxyl-termini of crustacean hyperglycemic hormone in the mud crab Scylla olivacea (Sco-CHH, both wild-type and point-mutated CHH peptides were produced with an amidated C-terminal end. Spectral analyses of circular dichroism, chromatographic retention time, and mass spectrometric analysis of the recombinant peptides indicate that they were close in conformation to native CHH and were produced with the intended substitutions. The recombinant peptides were subsequently used for an in vivo hyperglycemic assay. Two mutants (R13A and I69A rSco-CHH completely lacked hyperglycemic activity, with temporal profiles similar to that of vehicle control. Temporal profiles of hyperglycemic responses elicited by 4 mutants (I2A, F3A, D12A, and D60A Sco-CHH were different from that elicited by wild-type Sco-CHH; I2A was unique in that it exhibited significantly higher hyperglycemic activity, whereas the remaining 3 mutants showed lower activity. Four mutants (D4A, Q51A, E54A, and V72A rSco-CHH elicited hyperglycemic responses with temporal profiles similar to those evoked by wild-type Sco-CHH. In contrast, the glycine-extended version of V72A rSco-CHH (V72A rSco-CHH-Gly completely lost hyperglycemic activity. By comparing our study with previous ones of ion-transport peptide (ITP and molt-inhibiting hormone (MIH using deleted or point-mutated mutants, detail discussion is made regarding functionally important residues that are shared by both CHH and ITP (members of Group I of the CHH family, and those that discriminate CHH from ITP, and Group-I from Group-II peptides. Conclusions summarized in the present study provide insights into understanding of how functional diversification occurred within a peptide family of multifunctional members.

  17. Dorsal and Ventral Pathways for Prosody.

    Science.gov (United States)

    Sammler, Daniela; Grosbras, Marie-Hélène; Anwander, Alfred; Bestelmeyer, Patricia E G; Belin, Pascal

    2015-12-07

    Our vocal tone--the prosody--contributes a lot to the meaning of speech beyond the actual words. Indeed, the hesitant tone of a "yes" may be more telling than its affirmative lexical meaning. The human brain contains dorsal and ventral processing streams in the left hemisphere that underlie core linguistic abilities such as phonology, syntax, and semantics. Whether or not prosody--a reportedly right-hemispheric faculty--involves analogous processing streams is a matter of debate. Functional connectivity studies on prosody leave no doubt about the existence of such streams, but opinions diverge on whether information travels along dorsal or ventral pathways. Here we show, with a novel paradigm using audio morphing combined with multimodal neuroimaging and brain stimulation, that prosody perception takes dual routes along dorsal and ventral pathways in the right hemisphere. In experiment 1, categorization of speech stimuli that gradually varied in their prosodic pitch contour (between statement and question) involved (1) an auditory ventral pathway along the superior temporal lobe and (2) auditory-motor dorsal pathways connecting posterior temporal and inferior frontal/premotor areas. In experiment 2, inhibitory stimulation of right premotor cortex as a key node of the dorsal stream decreased participants' performance in prosody categorization, arguing for a motor involvement in prosody perception. These data draw a dual-stream picture of prosodic processing that parallels the established left-hemispheric multi-stream architecture of language, but with relative rightward asymmetry. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Root fractures

    DEFF Research Database (Denmark)

    Andreasen, Jens Ove; Christensen, Søren Steno Ahrensburg; Tsilingaridis, Georgios

    2012-01-01

    The purpose of this study was to analyze tooth loss after root fractures and to assess the influence of the type of healing and the location of the root fracture. Furthermore, the actual cause of tooth loss was analyzed.......The purpose of this study was to analyze tooth loss after root fractures and to assess the influence of the type of healing and the location of the root fracture. Furthermore, the actual cause of tooth loss was analyzed....

  19. Increased susceptibility to amyloid-β toxicity in rat brain microvascular endothelial cells under hyperglycemic conditions.

    Science.gov (United States)

    Carvalho, Cristina; Katz, Paige S; Dutta, Somhrita; Katakam, Prasad V G; Moreira, Paula I; Busija, David W

    2014-01-01

    We hypothesized that hyperglycemia-induced mitochondrial dysfunction and oxidative stress are closely associated with amyloid-β peptide (Aβ) toxicity in endothelial cells. Brain microvascular endothelial cells from rat (RBMEC) and mice (MBMEC) were isolated from adult Sprague-Dawley rats and homozygous db/db (Leprdb/Leprdb) and heterozygous (Dock7m/Leprdb) mice, and cultured under normo- and hyperglycemic conditions for 7 d followed by 24 h exposure to Aβ1-40. Some experiments were also performed with two mitochondrial superoxide (O2•-) scavengers, MitoTempo and Peg-SOD. Cell viability was measured by the Alamar blue assay and mitochondrial membrane potential (ΔΨm) by confocal microscopy. Mitochondrial O2•- and hydrogen peroxide (H2O2) production was assessed by fluorescence microscopy and H2O2 production was confirmed by microplate reader. Hyperglycemia or Aβ1-40 alone did not affect cell viability in RBMEC. However, the simultaneous presence of high glucose and Aβ1-40 reduced cell viability and ΔΨm, and enhanced mitochondrial O2•- and H2O2 production. MitoTempo and PEG-SOD prevented Aβ1-40 toxicity. Interestingly, MBMEC presented a similar pattern of alterations with db/db cultures presenting higher susceptibility to Aβ1-40. Overall, our results show that high glucose levels increase the susceptibility of brain microvascular endothelial cells to Aβ toxicity supporting the idea that hyperglycemia is a major risk factor for vascular injury associated with AD.

  20. Crustacean hyperglycemic hormone (cHH as a modulator of aggression in crustacean decapods.

    Directory of Open Access Journals (Sweden)

    Laura Aquiloni

    Full Text Available Biogenic amines, particularly serotonin, are recognised to play an important role in controlling the aggression of invertebrates, whereas the effect of neurohormones is still underexplored. The crustacean Hyperglycemic Hormone (cHH is a multifunctional member of the eyestalk neuropeptide family. We expect that this neuropeptide influences aggression either directly, by controlling its expression, or indirectly, by mobilizing the energetic stores needed for the increased activity of an animal. Our study aims at testing such an influence and the possible reversion of hierarchies in the red swamp crayfish, Procambarus clarkii, as a model organism. Three types of pairs of similarly sized males were formed: (1 'control pairs' (CP, n = 8: both individuals were injected with a phosphate saline solution (PBS; (2 'reinforced pairs' (RP, n = 9: the alpha alone was injected with native cHH, and the beta with PBS; (3 'inverted pairs' (IP, n = 9: the opposite of (2. We found that, independently of the crayfish's prior social experience, cHH injections induced (i the expression of dominance behaviour, (ii higher glycemic levels, and (iii lower time spent motionless. In CP and RP, fight intensity decreased with the establishment of dominance. On the contrary, in IP, betas became increasingly likely to initiate and escalate fights and, consequently, increased their dominance till a temporary reversal of the hierarchy. Our results demonstrate, for the first time, that, similarly to serotonin, cHH enhances individual aggression, up to reverse, although transitorily, the hierarchical rank. New research perspectives are thus opened in our intriguing effort of understanding the role of cHH in the modulation of agonistic behaviour in crustaceans.

  1. Cyanobacterial pigments as natural anti-hyperglycemic agents: An in vitro study

    Directory of Open Access Journals (Sweden)

    Tonmoy Ghosh

    2016-08-01

    Full Text Available Traditional medicines for controlling postprandial hyperglycemia includes herbs and plant extracts as well as synthetic drugs like acarbose. Synthetic drug molecules frequently have side effects such as flatulence and diarrhea. Cyanobacterial pigments have excellent anti-oxidant and free radical scavenging properties. Thus, α-amylase and α-glucosidase inhibiting activities of purified pigments and crude extracts from three cyanobacterial species, Lyngbya, Microcoleus and Synechocystis sp., were investigated. Lyngbya extract had the highest total anti-oxidant activity (TAC before digestion (48.26 ± 0.04 µg AAE ml-1 while purified lycopene had the highest TAC after digestion (154.16 ± 0.96 µg AAE ml-1. The Microcoleus extract had the highest ABTS scavenging activity before digestion (98.23 ± 0.25 % while purified C-phycocyanin (C-PC had the highest ABTS scavenging after digestion (99.69 ±0.04 %. None of the digested or undigested extracts performed better than acarbose in inhibiting α-amylase but the digested Microcoleus extract was able to inhibit its activity by ~35 %. The purified pigments gave inhibitory activities ranging from ~ 8 – 16 %. The Lyngbya extract had the highest inhibitory activity against α-glucosidase both before and after digestion (62.22 ± 0.02 and 97.82 ± 0.03 % respectively. Purified C-phycoerythrin (C-PE, C-PC, lycopene and myxoxanthophyll could inhibit α-glucosidase in a range of ~83 – 96 %. Considering the potent inhibitory activities of purified pigments against both α-amylase and α-glucosidase, cyanobacterial pigments could be used as food additives for their dual advantage of anti-oxidant and anti-hyperglycemic activities.

  2. Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kruljac, Ivan; Ćaćić, Miroslav; Ćaćić, Petra; Ostojić, Vedran; Štefanović, Mario; Šikić, Aljoša; Vrkljan, Milan

    2017-01-01

    Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department. Cox proportional hazard models were used to analyze the link between patient characteristics and mortality. During an observation time of 33.4 months, death of any cause occurred in 40.9 % of the non-ketotic hyperglycemia group and 30.2 % of the DK group (hazard ratio in the diabetic ketosis group, 0.63; 95 % confidence interval 0.48-0.82; P = 0.0005). Patients with diabetic ketosis had a lower incidence of symptomatic heart failure and had improved renal function. They used less furosemide and antihypertensive drugs, more metformin and lower insulin doses, all of which was independently associated with decreased mortality. Plasma glucose and glycated hemoglobin levels were similar in both groups. Patients with hyperglycemic crisis and diabetic ketosis have decreased all-cause mortality when compared to those with non-ketotic hyperglycemia. diabetic ketosis might be a compensatory mechanism rather than a complication in patients with hyperglycemic crises, but further prospective studies are warranted.

  3. Effects of Pycnogenol® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study.

    Science.gov (United States)

    Hu, S; Belcaro, G; Cornelli, U; Luzzi, R; Cesarone, M; Dugall, M; Feragalli, B; Errichi, B; Ippolito, E; Grossi, M; Hosoi, M; Gizzi, G; Trignani, M

    2015-02-01

    This registry study aimed to evaluate the effects of supplementation with pycnogenol on altered endothelial function (EF) in borderline hypertensive, hyperlipidemic and hyperglycemic subjects without atherosclerotic changes in their main arteries and no coronary artery disease. Flow mediated dilatation (FMD) and endothelium-independent (EID) dilatation were measured with brachial ultrasound after occlusion. Also, after occlusion, laser Doppler (LDF) flux and distal straingauge flow were measured. Oxidative stress (oxstress) was evaluated at 8 and 12 weeks. 93 subjects with borderline symptoms were enrolled into the study: 32 hypertensives, 31 hyperlipidemics, 30 hyperglycemics. All participants were instructed to follow the best available management to control their symptoms. In addition to best management, half of the subjects in each group used 150 mg/day Pycnogenol(®). 31 normal subjects were included as control. After 12 weeks metabolic values and blood pressure were back to normal in all subjects. Values were slightly better under Pycnogenol(®). FMD increased after 8 weeks from an average 5.3;3.4% to 8.2;2.2% with a further increase to 8.8;3.1% (PPycnogenol(®) at 8 weeks and 12 weeks. The final flux increase was not different from normal values. In controls flux after occlusion was not improved at 8 weeks; there was a significant but minor increase at 12 weeks. Flux increases were superior in all Pycnogenol(®) subjects. In Pycnogenol(®) subjects, limb flow after occlusion increased at 8 weeks with a further increase at 12 weeks. In controls inclusion flow after occlusion was comparable at 8 and 12 weeks. Oxidative stress was significantly decreased in Pycnogenol(®) subjects at 8 and 12 weeks. Minor differences were observed in controls. This open registry study indicates that Pycnogenol(®) improves EF in preclinical, borderline subjects in a macro-microcirculatory model. This observation may suggest an important preventive possibility for borderline

  4. The Main Symptoms in Dorsal Sleep Apnea - Hypopnea Syndrome

    Directory of Open Access Journals (Sweden)

    Mihaela Alexandra POP

    2014-09-01

    Full Text Available OSAHS is a chronic, multifactorial disease, accompanied by significant and complex symptoms. The aim of this study was to evaluate the relationship between OSAHS and dorsal AHI in order to improve early diagnosis of dorsal sleep apnea-hypopnea syndrome. There were significant statistical differences between: the dorsal AHI Mean of the group without excessive daytime sleepiness as opposed to the dorsal AHI Mean of the group with excessive daytime sleepiness; the dorsal AHI Mean of the group without snoring as opposed to the dorsal AHI Mean of the group with snoring; the dorsal AHI Mean of the group without restless sleep as opposed to the dorsal AHI Mean of the group with restless sleep; the dorsal AHI Mean of the group without dyspnea as opposed to the dorsal AHI Mean of the group with dyspnea; the dorsal AHI Mean of the group without night sweats as opposed to the dorsal AHI Mean of the group with night sweats; the dorsal AHI Mean of the group without irritability as opposed to the dorsal AHI Mean of the group with irritability and the dorsal AHI Mean of the group without nightmares as opposed to the dorsal AHI Mean of the group with nightmares. Through this study we highlighted that excessive daytime sleepiness and snoring are prevalent symptoms in dorsal OSAHS. The presence of these symptoms in patients with sleep disorders may improve early diagnosis and the choice of an appropriate treatment for dorsal sleep apnea- hypopnea syndrome, thus participating in improving the patient’s life quality

  5. Assessment of radiographer CT-guided dorsal ganglion block

    Energy Technology Data Exchange (ETDEWEB)

    Booth, T.C., E-mail: tombooth@doctors.org.uk [Department of Radiology, Royal Free Hospital NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Edwards, D.; Platts, A.D.; Savy, L.E. [Department of Radiology, Royal Free Hospital NHS Trust, Pond Street, London NW3 2QG (United Kingdom)

    2011-08-15

    Purpose: Radiographer-performed, CT-guided, therapeutic dorsal ganglion block (DGB) for lumbar radiculopathy was prospectively evaluated for firstly, short-term pain outcomes and secondly, complications. Methods: A prospective outcome audit was undertaken for all patients with radiculopathic pain undergoing radiographer-performed CT-guided DGB over a 12 month period. The indicators and standards were derived from published evidence. The complications were analysed by a neuroradiologist retrospectively. Findings: The pain indicator was defined as 'the percentage of patients referred for CT-guided DGB experiencing improvement or resolution of pain at two weeks post-procedure'. The standard chosen was 64% thus with an outcome of 67% the target was achieved. The complication indicator was defined as 'the percentage of all patients referred for CT-guided DGB who were complication-free over two weeks'. The standard chosen was 97% thus with an outcome of 81% the target was not achieved. Complications resulted from positioning or inaccurate nerve root selection. Conclusion: Radiographer CT-guided DGB is effective in improving or removing pain at two weeks post-procedure. It is safe and not associated with major complications. However, less patients were complication-free following DGB than would be expected. Pre-procedural review of the patient's MRI by a neuroradiologist is recommended to avoid incorrect nerve root selection.

  6. Transseptal dorsal approaches to the wrist.

    Science.gov (United States)

    Zemirline, Ahmed; Hoël, Gérard; Naïto, Kiyohito; Uguen, Arnaud; Liverneaux, Philippe; Le Nen, Dominique

    2013-04-01

    The dorsal approach to the wrist is the exposure of choice for most of the surgical procedures on the radiocarpal and intercarpal joints. Contrary to the volar approach, it encounters neither the main arteries nor the motor nerve branch. However, the dorsal approach goes necessarily through the extensor retinaculum. We describe two transseptal dorsal approaches that pass through the extensor retinaculum in the thickness of a septum between two compartments. A virtual space was developed beneath the infratendinous retinaculum (which is a deep layer covering the floor of the extensor compartments) to expose the periosteum, the ligaments and the joint capsule without opening the extensor compartments. Twenty cadaveric wrists have been dissected to study the feasibility of the two transseptal approaches. Ten wrists were exposed through a 3-4 transseptal approach, passing through the extensor retinaculum in the thickness of the septum between the third and fourth compartments. Ten wrists were exposed through a 4-5 transseptal approach, passing through the extensor retinaculum in the thickness of the septum between the fourth and fifth compartments. The extent of violations of extensor compartments and joint capsule, and the exposed anatomical structures were noted. At the end of each dissection, the whole extensor system was outrightly removed for histological study. The feasibility of the transseptal approaches was demonstrated for all the dissected wrists. The dissection plane beneath the infratendinous retinaculum was macroscopically and microscopically highlighted. The transseptal approaches provide a good exposure to the dorsal side of the wrist joint, without opening the extensor tendon compartments.

  7. Complex Dorsal Metacarpophalangeal Joint Dislocation of Index ...

    African Journals Online (AJOL)

    Complex dorsal metacarpophalangeal dislocation is uncommon. The failure of closed reduction is established. This case report highlights the problem within context of a developing country. The various factors responsible for irreducibilty are reviewed and approaches to surgical treatment discussed in the review of world ...

  8. Effects of Exercise in the Fasted and Postprandial State on Interstitial Glucose in Hyperglycemic Individuals

    Science.gov (United States)

    Nygaard, Håvard; Rønnestad, Bent R.; Hammarström, Daniel; Holmboe-Ottesen, Gerd; Høstmark, Arne T.

    2017-01-01

    The purpose of the present study was to test if one bout of moderate exercise performed in either the fasted or the postprandial state affects glucose values measured over 22 hours. Twelve participants diagnosed with hyperglycemia not using antidiabetic medications underwent 3 test days in a randomized cross-over design encompassing one test day without exercise, one test day with 60 min of treadmill walking prior to breakfast, and one test day with an identical bout of exercise 30 min after the start of breakfast. Continuous glucose monitoring was performed until the next morning (>22 hours). There was no significant effect of type of test day on the area under the glucose curve for the entire 22 hours period (p = 0.111). None of the exercise interventions had a significant effect on the area under the glucose curve after breakfast, lunch or dinner. However, the postprandial exercise bout tended to decrease the area under the glucose curve after the evening meal compared to the fasted exercise bout (24.2 ± 6.2 vs. 27.6 ± 6.0 mmol·hour·L-1, p = 0.031). Furthermore, the postprandial exercise decreased the mean of the 10 highest glucose values measured in each individual (8.6 ± 1.9 mmol·L-1) over 22 hours compared to both the control day (9.3 ± 2.1 mmol.L-1) and the day with fasted exercise (9.6 ± 1.7 mmol·L-1, p = 0.012 and 0.009 respectively). Postprandial exercise also decreased the glycemic variability compared to the control day (1.22 ± 0.49 vs. 1.58 ± 0.52 mmol·L-1, p = 0.015). We conclude that performing moderate exercise in the postprandial state after breakfast, but not in the fasted state, decreases glucose excursions during the subsequent 22 hours period in hyperglycemic individuals not using antidiabetic medications. Key points Persons with postprandial hyperglycemia are at increased risk for cardiovascular disease. Performing moderate exercise in the postprandial state but not post-absorptive state decreases peak postprandial glucose values

  9. Effects of Exercise in the Fasted and Postprandial State on Interstitial Glucose in Hyperglycemic Individuals

    Directory of Open Access Journals (Sweden)

    Håvard Nygaard, Bent R. Rønnestad, Daniel Hammarström, Gerd Holmboe-Ottesen, Arne T. Høstmark

    2017-06-01

    Full Text Available The purpose of the present study was to test if one bout of moderate exercise performed in either the fasted or the postprandial state affects glucose values measured over 22 hours. Twelve participants diagnosed with hyperglycemia not using antidiabetic medications underwent 3 test days in a randomized cross-over design encompassing one test day without exercise, one test day with 60 min of treadmill walking prior to breakfast, and one test day with an identical bout of exercise 30 min after the start of breakfast. Continuous glucose monitoring was performed until the next morning (>22 hours. There was no significant effect of type of test day on the area under the glucose curve for the entire 22 hours period (p = 0.111. None of the exercise interventions had a significant effect on the area under the glucose curve after breakfast, lunch or dinner. However, the postprandial exercise bout tended to decrease the area under the glucose curve after the evening meal compared to the fasted exercise bout (24.2 ± 6.2 vs. 27.6 ± 6.0 mmol·hour·L-1, p = 0.031. Furthermore, the postprandial exercise decreased the mean of the 10 highest glucose values measured in each individual (8.6 ± 1.9 mmol·L-1 over 22 hours compared to both the control day (9.3 ± 2.1 mmol.L-1 and the day with fasted exercise (9.6 ± 1.7 mmol·L-1, p = 0.012 and 0.009 respectively. Postprandial exercise also decreased the glycemic variability compared to the control day (1.22 ± 0.49 vs. 1.58 ± 0.52 mmol·L-1, p = 0.015. We conclude that performing moderate exercise in the postprandial state after breakfast, but not in the fasted state, decreases glucose excursions during the subsequent 22 hours period in hyperglycemic individuals not using antidiabetic medications.

  10. Effect of VCO to leucocyte differential count, glucose levels and blood creatinine of hyperglycemic and ovalbumin sensitized Mus musculus Balb/c

    Directory of Open Access Journals (Sweden)

    RUBEN DHARMAWAN

    2009-03-01

    Full Text Available Abstract. Handajani NS, Dharmawan R. 2009. Effect of VCO to leucocyte differential count, glucose levels and blood creatinine of hyperglycemic and ovalbumin sensitized Mus musculus Balb/c. Nusantara Bioscience 1: 1-8. Chemical medicines and insulin can decrease glucose blood level on hyperglycemic patients with macro vascular side effect. Diabetes and allergy incidences are influenced by quality and quantity of leucocytes. Lauric acid within VCO reports decreased glucose blood level of diabetes and some allergy incidents. The purpose of the study is to know the effect of VCO on glucose blood level, differential leucocytes count and creatinine blood level on hyperglycemic and normoglicemic ovalbumin sensitized mice. Forty five (45 male (mice of Mus musculus Balb/c with average weight of 35 g are divided into 9 groups with 5 repetitions, those are 4 non alloxan groups and 5 alloxan induced hyperglycemic groups. On 22nd day to 36th day they are sensitize to ovalbumin as allergen. Blood sample was obtained by orbital vena using heparin as anti coagulant in order measuring glucose blood level by GOD method to 6 times, on 1st, 4th, 18th, 22nd, 32nd and 37th days, then are tested by ANOVA followed by DMRT 0.05. On 37th day, differential leucocytes are determined, blood level are counted, and then compared to normal value. The result of this study were that within differential leucocytes count of hyperglycemic mice, neutrophile percentage were much lower than the normal value (3.22%, and lymphocyte percentage were much higher than the normal value (94.54%. Consumed 0.003 mL/35 g VCO more 18 days decreased glucose blood level on hyperglycemic mice, decreased basophile percentage of ovalbumin sensitized mice, normalized neutrophile percentage no increased creatinine blood level.

  11. Curcumin Upregulates Antioxidant Defense, Lon Protease, and Heat-Shock Protein 70 Under Hyperglycemic Conditions in Human Hepatoma Cells.

    Science.gov (United States)

    Gounden, Shivona; Chuturgoon, Anil

    2017-05-01

    Sirtuin 3 (SIRT3) regulates mitochondrial antioxidant (AO) defense and improves mitochondrial disorders. Curcumin protects mitochondria; however, the mechanisms need investigation. We postulated that curcumin increases AO defense under hyperglycemic conditions in HepG2 cells through SIRT3-mediated mechanisms. Cell viability was determined in HepG2 cells cultured with 5 mM glucose, 19.9 mM mannitol, vehicle control, 10 mM glucose, and 30 mM glucose in the absence or presence of curcumin for 24 h. SIRT3, nuclear factor-kappa B (NF-κB), heat-shock protein 70 (Hsp70), and Lon protein expressions were determined using western blot. Transcript levels of SIRT3, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), cAMP response element-binding protein (CREB), glutathione peroxidase 1 (GPx1), and superoxide dismutase 2 (SOD2) were measured by quantitative polymerase chain reaction. Cell viability, SIRT3 protein expression, transcript levels of SIRT3, PGC-1α, CREB, GPx1, and SOD2 and protein expressions of NF-κB, Lon, and Hsp70 were significantly increased in the curcumin-treated hyperglycemic groups. Since curcumin and SIRT3 both improve mitochondrial function and AO defense, SIRT3 may be involved in the protective effects of curcumin.

  12. Xenon inhibits excitatory but not inhibitory transmission in rat spinal cord dorsal horn neurons

    Science.gov (United States)

    2010-01-01

    Background The molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method. Results In vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist. Conclusions Xenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon. PMID:20444263

  13. Comparative anatomy of the dorsal hump in mature Pacific salmon.

    Science.gov (United States)

    Susuki, Kenta; Ban, Masatoshi; Ichimura, Masaki; Kudo, Hideaki

    2017-07-01

    Mature male Pacific salmon (Genus Oncorhynchus) demonstrate prominent morphological changes, such as the development of a dorsal hump. The degree of dorsal hump formation depends on the species in Pacific salmon. It is generally accepted that mature males of sockeye (O. nerka) and pink (O. gorbuscha) salmon develop most pronounced dorsal humps. The internal structure of the dorsal hump in pink salmon has been confirmed in detail. In this study, the dorsal hump morphologies were analyzed in four Pacific salmon species inhabiting Japan, masu (O. masou), sockeye, chum (O. keta), and pink salmon. The internal structure of the dorsal humps also depended on the species; sockeye and pink salmon showed conspicuous development of connective tissue and growth of bone tissues in the dorsal tissues. Masu and chum salmon exhibited less-pronounced increases in connective tissues and bone growth. Hyaluronic acid was clearly detected in dorsal hump connective tissue by histochemistry, except for in masu salmon. The lipid content in dorsal hump connective tissue was richer in masu and chum salmon than in sockeye and pink salmon. These results revealed that the patterns of dorsal hump formation differed among species, and especially sockeye and pink salmon develop pronounced dorsal humps through both increases in the amount of connective tissue and the growth of bone tissues. In contrast, masu and chum salmon develop their dorsal humps by the growth of bone tissues, rather than the development of connective tissue. © 2017 Wiley Periodicals, Inc.

  14. Dammarane-type triterpene extracts of Panax notoginseng root ameliorates hyperglycemia and insulin sensitivity by enhancing glucose uptake in skeletal muscle.

    Science.gov (United States)

    Kitamura, Kumiko; Takamura, Yusuke; Iwamoto, Taku; Nomura, Mitsuru; Iwasaki, Hideaki; Ohdera, Motoyasu; Murakoshi, Michiaki; Sugiyama, Keikichi; Matsuyama, Kazuki; Manabe, Yasuko; Fujii, Nobuharu L; Fushiki, Tohru

    2017-02-01

    Skeletal muscle is an important organ for controlling the development of type 2 diabetes. We discovered Panax notoginseng roots as a candidate to improve hyperglycemia through in vitro muscle cells screening test. Saponins are considered as the active ingredients of ginseng. However, in the body, saponins are converted to dammarane-type triterpenes, which may account for the anti-hyperglycemic activity. We developed a method for producing a dammarane-type triterpene extract (DTE) from Panax notoginseng roots and investigated the extract's potential anti-hyperglycemic activity. We found that DTE had stronger suppressive activity on blood glucose levels than the saponin extract (SE) did in KK-Ay mice. Additionally, DTE improved oral glucose tolerance, insulin sensitivity, glucose uptake, and Akt phosphorylation in skeletal muscle. These results suggest that DTE is a promising agent for controlling hyperglycemia by enhancing glucose uptake in skeletal muscle.

  15. Deep dorsal vein arterialisation in vascular impotence.

    Science.gov (United States)

    Wespes, E; Corbusier, A; Delcour, C; Vandenbosch, G; Struyven, J; Schulman, C C

    1989-11-01

    A series of 12 patients with vasculogenic impotence (4 arterial lesions; 8 arterial and venous lesions) underwent deep dorsal vein arterialisation after pre-operative assessment by a multidisciplinary approach. Cumulative graft patency was 58% (7 of 12 patients) up to 21 months but only 4 patients developed almost normal erections. Digital angiography, with and without the intracavernous injection of papaverine, was performed during follow-up to determine the vascular physiological status. At flaccidity, the corpora cavernosa were never opacified in the absence of a venocorporeal shunt. The penile glans was always visualised. Opacification of the deep dorsal vein and the circumflex system decreased with penile rigidity, resulting from their compression between Buck's fascia and the tunica albuginea. Intracavernous pressure recorded before and after the surgical procedure showed a marked increase when a caverno-venous shunt was performed. Hypervascularisation of the glans occurred in 2 cases. The relevance of this new surgical technique and its functional mechanism are discussed.

  16. Giant cell tumor of dorsal vertebral body

    Directory of Open Access Journals (Sweden)

    Rakesh Redhu

    2012-01-01

    Full Text Available A 30-year-old female patient presented with complaints of backache, weakness in both lower limbs and bladder/bowel dysfunction. Imaging showed an osteolytic lesion at tenth dorsal (D10 vertebra with anterior compression on the spinal cord. Complete intralesional tumor excision with reconstruction was carried out using the anterolateral extrapleural approach. Histopathological examination was suggestive of giant cell tumor (GCT. Because of complete intralesional tumor excision and fear of post-radiation osteonecrosis of bone used for delayed bony union, a conservative approach was used, and radiation therapy was not given. After one year of follow-up patient is doing well without any recurrence of the tumor and is ambulant with support. GCT of dorsal vertebral body is an uncommon entity and total en bloc excision is difficult. Therefore, the treatment strategy is not well-defined. We discuss in brief about incidence, presentation and various treatment modalities available for spinal GCT.

  17. Attentional functions in dorsal and ventral simultanagnosia.

    Science.gov (United States)

    Duncan, John; Bundesen, Claus; Olson, Andrew; Humphreys, Glyn; Ward, Robert; Kyllingsbæk, Søren; van Raamsdonk, Monique; Rorden, Chris; Chavda, Swarup

    2003-12-01

    Whole report of brief letter arrays is used to analyse basic attentional deficits in dorsal and ventral variants of simultanagnosia. Using Bundesen's Theory of Visual Attention (TVA), a number of previous theoretical suggestions are formalised and tested, including primary deficit in processing more than one display element, attentional stickiness, foveal bias, and global weakness of the visual representation. Interestingly, data from two cases, one dorsal and one ventral, show little true deficit in simultaneous perception, or selective deficit in those TVA parameters (short-term memory capacity, attentional weighting) specifically associated with multi-element displays. Instead there is a general reduction in speed of visual processing (processing rate in TVA), effective even for a single display element but compounded when two or more elements compete.

  18. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, Arnulf; Vaupel, Peter; Stockinger, Marcus; Schmidberger, Heinz [University Medical Center, Department of Radiooncology and Radiotherapy, Mainz (Germany); Struss, Hans-Garlich [University Medical Center, Department of Laboratory Medicine, Mainz (Germany); Giese, Alf [University Medical Center, Department of Neurosurgery, Mainz (Germany)

    2014-10-15

    In comparison to normal brain tissue, glioblastomas exhibit significantly increased glucose uptake. Brain edema is a common complication during adjuvant chemoradiotherapy, leading to a requirement for glucocorticoid treatment. Glucocorticoid treatment frequently causes considerable deregulation of blood glucose levels. Therefore, episodes of hyperglycemia may contribute to radio- and/or chemoresistance. This study comprises a retrospective analysis of the influence of hyperglycemic episodes (HEs) during adjuvant therapy on the overall survival of 106 glioblastoma multiforme patients. The occurrence of one or more deregulated blood glucose value(s) > 10 mM is associated with a reduction in median overall survival from 16.7 to 8.8 months. A significantly poorer overall survival of patients with hyperglycemia could also be detected in subgroup analyses of patients with complete tumor resection and complete treatment according to the EORTC 22891/26891 trial protocol, as well as in a multivariate Cox proportional hazards analysis. A history of diabetes mellitus had no influence on prognosis. Our data suggest that the observed negative impact of elevated blood glucose levels on overall survival may not solely be explained by the patients' poorer general condition; the elevated blood glucose concentration itself may play a pathogenetic role. This could be due to increased activity of antioxidant systems, elevated expression of DNA damage response proteins and protection of hypoxic tumor cells against apoptosis combined with hypoxia-mediated radioresistance. A possible prognostic impact of elevated blood glucose levels during the period of adjuvant (chemo-) radiotherapy of glioblastoma should be evaluated in a prospective clinical trial. (orig.) [German] Glioblastome zeigen im Vergleich mit normalem Gehirngewebe eine deutlich vermehrte Glukoseaufnahme. Im Rahmen der adjuvanten Radio(chemo)therapie von Glioblastomen treten vielfach Hirnoedeme auf, die eine

  19. Anti-hyperglycemic activity of Centella asiatica is partly mediated by carbohydrase inhibition and glucose-fiber binding.

    Science.gov (United States)

    Kabir, Ashraf Ul; Samad, Mehdi Bin; D'Costa, Ninadh Malrina; Akhter, Farjana; Ahmed, Arif; Hannan, J M A

    2014-01-18

    Centella asiatica (C. asiatica) was previously reported to have anti-hyperglycemic effects in animal diabetic model rats. However, its activity on organ and tissue level remains unstudied. Our study aims at exploring the possible effects, C. asiatica extract and insoluble fiber has on carbohydrate absorption, insulin secretion, insulin sensitivity and glucose utilization. For primary evaluation of anti-hyperglycemic activity, we measured Fasting Blood Glucose and performed Glucose Tolerance Test, in type 2 diabetic rats. To further study the pancreatic effect and glucose utilization, plasma insulin concentration, insulin secreted from isolated rat islets and liver glycogen were assayed. Effect on carbohydrate break down was assayed using intestinal disaccharidase enzyme, α-amylase inhibition assays and Six-Segment study of the GI tract. Effect of C. asiatica on glucose absorption was studied by an in-situ, perfused, intestinal model in rats and by glucose-fiber binding assay. Gastrointestinal motility was seen by a BaSO4 milk traverse test. Additionally, a complete lipid profile assay, after a chronic study, was conducted. C. asiatica showed no significant change in insulin secretion in-vivo and in isolated rat islets. Additionally, no effect of the extract was seen on liver glycogen deposition. Retarded glucose absorption was seen in the in-situ perfused rat intestinal model at a dose. The extract was also found to inhibit action of both intestinal disaccharidase and α-amylase. This was confirmed, yet again, via the Six Segment study, where sucrose digestion was found to be inhibited throughout the length of the GI Tract. Significant glucose-fiber binding was demonstrated in the in-vitro models. During the chronic study, body mass of C. asiatica treated Type 2 diabetic rats returned to normal and their polydipsic and polyphagic conditions were also improved. Chronic treatment of C. asiatica also improved subject's lipid profile. A combination of in-vitro, in

  20. Pain-related synaptic plasticity in spinal dorsal horn neurons: role of CGRP

    Directory of Open Access Journals (Sweden)

    Willis William D

    2006-09-01

    Full Text Available Abstract Background The synaptic and cellular mechanisms of pain-related central sensitization in the spinal cord are not fully understood yet. Calcitonin gene-related peptide (CGRP has been identified as an important molecule in spinal nociceptive processing and ensuing behavioral responses, but its contribution to synaptic plasticity, cellular mechanisms and site of action in the spinal cord remain to be determined. Here we address the role of CGRP in synaptic plasticity in the spinal dorsal horn in a model of arthritic pain. Results Whole-cell current- and voltage-clamp recordings were made from substantia gelatinosa (SG neurons in spinal cord slices from control rats and arthritic rats (> 6 h postinjection of kaolin/carrageenan into the knee. Monosynaptic excitatory postsynaptic currents (EPSCs were evoked by electrical stimulation of afferents in the dorsal root near the dorsal root entry zone. Neurons in slices from arthritic rats showed increased synaptic transmission and excitability compared to controls. A selective CGRP1 receptor antagonist (CGRP8-37 reversed synaptic plasticity in neurons from arthritic rats but had no significant effect on normal transmission. CGRP facilitated synaptic transmission in the arthritis pain model more strongly than under normal conditions where both facilitatory and inhibitory effects were observed. CGRP also increased neuronal excitability. Miniature EPSC analysis suggested a post- rather than pre-synaptic mechanism of CGRP action. Conclusion This study is the first to show synaptic plasticity in the spinal dorsal horn in a model of arthritic pain that involves a postsynaptic action of CGRP on SG neurons.

  1. Treatment of right dorsal ulcerative colitis in a horse.

    Science.gov (United States)

    Simmons, T R; Gaughan, E M; Ducharme, N G; Dill, S G; King, J M; Anderson, W I

    1990-02-01

    Excessive administration of phenylbutazone was associated with development of right dorsal ulcerative colitis. The clinical signs of right dorsal colitis include chronic colic and weight loss. The laboratory abnormalities include panhypoproteinemia and a high WBC count in the abdominal fluid. Medical management of the chronic colic and protein-losing enteropathy associated with the ulcerative lesions in the right dorsal colon and surgical bypass of the right dorsal colon did not result in long-term resolution of clinical signs. Resection of the ulcerated right dorsal colon through a right lateral approach at the 16th rib resulted in resolution of intestinal protein loss and colic. The results of this case suggest that surgical resection of the ulcerated right dorsal colon may be the recommended treatment for right dorsal ulcerative colitis.

  2. Cell specificity of the cytoplasmic Ca2+ response to tolbutamide is impaired in beta-cells from hyperglycemic mice

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Larsson-Nyrén, Gerd; Lindström, Per

    2006-01-01

    -cells and if so, whether it is disturbed in beta-cells from hyperglycemic ob/ob and db/db mice. Zn(2+) outflow measurements were used to study the correlation between Ca(2+) response and insulin secretion in individual beta-cells. Tolbutamide and arginine induced cell-specific Ca(2+) responses in lean mouse beta...... of Ca(2+) response was cell-specific, not the timing. The lag time of tolbutamide-induced insulin secretion was cell-specific in lean mouse beta-cells but not in ob/ob mouse cells. Therefore, cell specificity seems to be a robust mechanism, and probably important for an adequate beta-cell function...

  3. Isolation and primary structure of two peptides with cardioacceleratory and hyperglycemic activity from the corpora cardiaca of Periplaneta americana.

    Science.gov (United States)

    Scarborough, R M; Jamieson, G C; Kalish, F; Kramer, S J; McEnroe, G A; Miller, C A; Schooley, D A

    1984-01-01

    Two cardioacceleratory peptides from the corpora cardiaca of Periplaneta americana have been purified by gel filtration and reversed-phase liquid chromatography, Based on analysis of the intact factors and their chymotryptic fragments, we have assigned the primary structure of these octapeptides as pGlu-Val-Asn-Phe-Ser-Pro-Asn-Trp-NH2, designated periplanetin CC-1, and pGlu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-NH2, designated periplanetin CC-2. They represent new members of a family of invertebrate peptides that includes locust adipokinetic hormone and crustacean red-pigment concentrating hormone. Both peptides show adipokinetic activity in grasshoppers and hyperglycemic activity in cockroaches. One of these peptides (CC-2) has provocative sequence homology with the NH2-terminal portion of glucagon. Images PMID:6591205

  4. Efficacy of Spirulina platensis in improvement of the reproductive performance and easing teratogenicity in hyperglycemic albino mice

    Science.gov (United States)

    Pankaj, Pranay Punj

    2015-01-01

    Objectives: The present study evaluates the therapeutic efficacy of cell suspension of Spirulina platensis (SP) on estrous cycle, fetal development and embryopathy in alloxan (AXN) induced hyperglycemic mice. Materials and Methods: Diabetes was induced by intra-peritoneal administration of AXN. Mice with blood glucose level above 200 mg/dl were divided into Group I (control), Group II (diabetic control), Group III (diabetic control mice fed with SP), and Group IV (control mice fed with SP). Litter counts, estrous cycles, percent survival of litter, and gestation length were recorded. Results: In hyperglycemic mice, a significant (P < 0.05) increase in duration of diestrus (14.48%), estrus (84.21%), and metestrus (164.15%) with concomitant decrease in proestrus phase by 26.13% was recorded when compared with control. Reduction in litter count and survival of litter was 68.67% and 88.38%, respectively, whereas gestation length increased to 14.51% day in diabetic mice, but recovery in these parameters was observed (P < 0.05) when subjected to SP treatment. SP resulted in increased fertility rate from 77.5% to 82.5% and dropped off resorption of the fetus to 33.73% while the survival rate of offspring of diabetic mice went up to 88.89% from 83.61%. Conclusions: These findings suggest that SP is effective in improving the reproductive performance and easing teratogenic effects in diabetic mice and hence warrants further detailed dose-dependent studies to understand its mechanism of action. PMID:26285837

  5. Evaluation of the in vitro anti-hyperglycemic effect of Cinnamomum cassia derived phenolic phytochemicals, via carbohydrate hydrolyzing enzyme inhibition.

    Science.gov (United States)

    Kang, B-H; Racicot, K; Pilkenton, S J; Apostolidis, E

    2014-06-01

    Cinnamomum cassia (cinnamon) proanthocyanidins (PACs) are believed to have anti-hyperglycemic potential via stimulation of insulin sensitivity. The present study investigates the carbohydrate hydrolyzing enzyme inhibition of cinnamon PACs. Five grams of cinnamon bark powder were extracted in 100 mL acetone solution (CAE) (acetone: water: hydrochloric acid, 70:29.9:0.01) for 2 h at room temperature and in 100 mL deionized water for 30 min at 90 °C (CWE). PACs were purified from CAE using LH-20 (CAE-PAC) to be further evaluated. PAC contents were evaluated by 4-Dimethylaminocinnamaldehyde (DMAC) assay and yielded 795, 177 and 123 mg/g, for CAE-PAC, CAE and CWE respectively. The total phenolic contents of CAE and CWE were determined to be 152 and 134 mg/g respectively. All extracts were adjusted to the same PAC content (180, 90, 45 and 20 μg) and the inhibitory activity against rat α-glucosidase was determined. The CAE-PAC fraction had very low rat α-glucosidase inhibitory activity, CAE had the highest (IC50 0.474 mg/mL total phenolic (TP) basis) followed by CWE (IC50 0.697 mg/mL TP basis). The specific maltase and sucrase inhibitory activities were determined and CAE (IC50 0.38 and 0.10 mg/mL TP basis) had higher inhibition than CWE (IC50 0.74 and 0.37 mg/mL TP basis). Results suggest that the observed bioactivity is not PAC dependent and that CAE has a higher anti-hyperglycemic potential than CWE via inhibition of carbohydrate hydrolyzing enzymes.

  6. Infrared neural stimulation of human spinal nerve roots in vivo.

    Science.gov (United States)

    Cayce, Jonathan M; Wells, Jonathon D; Malphrus, Jonathan D; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B; Konrad, Peter E; Jansen, E Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

  7. Hair Growth Promotant Activity of Petroleum Ether Root Extract of ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Glycyrrhiza glabra root extract on hair growth in female Wistar rats. Methods: Female Wistar rats were used for the hair growth promotion studies. They were divided into three groups(n = 6) and their dorsal skin was completely denuded to completely remove hair. Paraffin oil (control), 2 ...

  8. PROJECTIONS OF DORSAL AND MEDIAN RAPHE NUCLEI TO DORSAL AND VENTRAL STRIATUM

    Directory of Open Access Journals (Sweden)

    G. R. Hassanzadeh G. Behzadi

    2007-08-01

    Full Text Available The ascending serotonergic projections are derived mainly from mesencephalic raphe nuclei. Topographical projections from mesencephalic raphe nuclei to the striatum were examined in the rat by the retrograde transport technique of HRP (horseradish peroxidase. In 29 rats stereotaxically injection of HRP enzyme were performed in dorsal and ventral parts of striatum separately. The extent of the injection sites and distribution of retrogradely labeled neuronal cell bodies were drawed on representative sections using a projection microscope. Following ipsilateral injection of HRP into the dorsal striatum, numerous labeled neurons were seen in rostral portion of dorsal raphe (DR nucleus. In the same level the cluster of labeled neurons were hevier through caudal parts of DR. A few neurons were also located in lateral wing of DR. More caudally some labeled neurons were found in lateral, medial line of DR. In median raphe nucleus (MnR the labeled neurons were scattered only in median portion of this nucleus. The ipsilateral injection of HRP into the ventral region of striatum resulted on labeling of numerous neurons in rostral, caudal and lateral portions of DR. Through the caudal extension of DR on 4th ventricle level, a large number of labeled neurons were distributed along the ventrocaudal parts of DR. In MnR, labeled neurons were observed only in median part of this nucleus. These findings suggest the mesencephalic raphe nuclei projections to caudo-putamen are topographically organized. In addition dorsal and median raphe nuclei have a stronger projection to the ventral striatum.

  9. Isolated dorsal dislocation of the tarsal naviculum.

    Science.gov (United States)

    Hamdi, Kaziz; Hazem, Ben Ghozlen; Yadh, Zitoun; Faouzi, Abid

    2015-01-01

    Isolated dislocation of the tarsal naviculum is an unusual injury, scarcely reported in the literature. The naviculum is surrounded by the rigid bony and ligamentous support hence fracture dislocation is more common than isolated dislocation. The mechanism and treatment options remain unclear. In this case report, we describe a 31 year old man who sustained an isolated dorsal dislocation of the left tarsal naviculum, without fracture, when he was involved in a motor vehicle collision. The reported mechanism of the dislocation is a hyper plantar flexion force applied to the midfoot, resulting in a transient disruption of the ligamentous support of the naviculum bone, with dorsal displacement of the bone. The patient was treated with open reduction and Krischner-wire fixation of the navicular after the failure of closed reduction. The wires were removed after 6 weeks postoperatively. Physiotherapy for stiffness and midfoot pain was recommended for 2 months. At 6 months postoperatively, limping, midfoot pain and weakness were reported, no X-ray abnormalities were found. The patient returned to his obvious activities with a normal range of motion.

  10. Isolated dorsal dislocation of the tarsal naviculum

    Directory of Open Access Journals (Sweden)

    Kaziz Hamdi

    2015-01-01

    Full Text Available Isolated dislocation of the tarsal naviculum is an unusual injury, scarcely reported in the literature. The naviculum is surrounded by the rigid bony and ligamentous support hence fracture dislocation is more common than isolated dislocation. The mechanism and treatment options remain unclear. In this case report, we describe a 31 year old man who sustained an isolated dorsal dislocation of the left tarsal naviculum, without fracture, when he was involved in a motor vehicle collision. The reported mechanism of the dislocation is a hyper plantar flexion force applied to the midfoot, resulting in a transient disruption of the ligamentous support of the naviculum bone, with dorsal displacement of the bone. The patient was treated with open reduction and Krischner-wire fixation of the navicular after the failure of closed reduction. The wires were removed after 6 weeks postoperatively. Physiotherapy for stiffness and midfoot pain was recommended for 2 months. At 6 months postoperatively, limping, midfoot pain and weakness were reported, no X-ray abnormalities were found. The patient returned to his obvious activities with a normal range of motion.

  11. Root resorption

    DEFF Research Database (Denmark)

    Kjaer, Inger

    2014-01-01

    formerly been demonstrated how demyelinization of the myelin sheaths in the peripheral nerves close to the root provoke resorption. Accordingly, conditions affecting these tissue layers can be associated not only with different morphologies but also with general symptoms and diseases (e.g., ectodermal...

  12. Root (Botany)

    Science.gov (United States)

    Robert R. Ziemer

    1981-01-01

    Plant roots can contribute significantly to the stability of steep slopes. They can anchor through the soil mass into fractures in bedrock, can cross zones of weakness to more stable soil, and can provide interlocking long fibrous binders within a weak soil mass. In deep soil, anchoring to bedrock becomes negligible, and lateral reinforcement predominates

  13. Association of Sleep Deprivation With Reduction in Insulin Sensitivity as Assessed by the Hyperglycemic Clamp Technique in Adolescents.

    Science.gov (United States)

    De Bernardi Rodrigues, Ana Maria; da Silva, Cleliani de Cassia; Vasques, Ana Carolina Junqueira; Camilo, Daniella Fernandes; Barreiro, Francieli; Cassani, Roberta Soares Lara; Zambon, Mariana Porto; Antonio, Maria Ângela Reis de Góes Monteiro; Geloneze, Bruno

    2016-05-01

    The association between short sleep duration and decreased insulin sensitivity in adolescents has been described. However, to our knowledge, no studies have investigated this association measuring insulin sensitivity by the hyperglycemic clamp technique. To compare the distributions of parameters of insulin resistance in adolescents with sleep deprivation vs adequate sleep, and to investigate the association between sleep deprivation and insulin sensitivity. Cross-sectional multicenter study using data from the Brazilian Metabolic Syndrome Study conducted from June 29, 2011, to December 3, 2014, at an obesity outpatient clinic at the University of Campinas and public schools, with a convenience sample of 615 adolescents aged 10 to 19.9 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for age and sex at the fifth percentile or higher. A subsample of 81 adolescents underwent the hyperglycemic clamp technique. The self-reported sleep duration was used to classify the population into 2 groups: adolescents with sleep deprivation (adolescents with adequate sleep (≥8 hours/night). Insulin sensitivity was assessed using the hyperglycemic clamp technique. Among the 615 adolescents (56.3% female; median age, 15.9 years [interquartile range, 12.9-17.8 years]) included in the sample, the mean (SD) sleep duration was 7.9 (1.7) hours/night. The adolescents with sleep deprivation (n = 257) compared with those with adequate sleep (n = 358) had a higher median (interquartile range) age (17.0 [15.4-18.3] vs 14.1 [11.8-16.9] years), BMI (25.0 [21.2-29.3] vs 23.1 [19.5-27.6]), waist circumference (83.0 [73.5-95.4] vs 79.0 [68.5-91.0] cm), sagittal abdominal diameter (17.9 [15.8-20.8] vs 17.0 [15.0-19.8] cm), neck circumference (35.2 [33.0-38.0] vs 33.0 [30.0-35.5] cm), uric acid level (4.9 [4.0-5.8] vs 4.5 [3.7-5.5] mg/dL), and white blood cell count (7000 [5900-8200] vs 6600 [5600-7800] cells/μL) (all P

  14. Lutein attenuates oxidative stress markers and ameliorates glucose homeostasis through polyol pathway in heart and kidney of STZ-induced hyperglycemic rat model.

    Science.gov (United States)

    Sharavana, Gurunathan; Joseph, G S; Baskaran, Vallikannan

    2017-12-01

    Lutein's role on chronic hyperglycemia-induced oxidative stress and associated glucose homeostasis in heart and kidney is limited. Purpose of the study is to investigate the effect of lutein on cardiac and renal polyol pathway enzymes and oxidative stress markers under hyperglycemia-induced oxidative stress condition using streptozotocin (STZ)-injected rat model. STZ-induced hyperglycemic (fasting blood glucose ≥11 mM) male Wistar rats were divided into two groups (n = 11/group). Group 1 received micellar lutein (39 nmol/day/rat) and group 2 (negative control) received micelle without lutein for 8 weeks. A separate group (no STZ injected) served as a positive control (n = 11/group). Oral glucose tolerance test (OGTT), biweekly urine glucose and activities of aldose reductase (AR) and sorbitol dehydrogenase (SDH) enzymes were assessed. Activities of antioxidant enzymes and antioxidant level were also evaluated. Lutein-administered hyperglycemic rats showed better glucose tolerance as evidenced with OGTT and biweekly urine glucose when compared to negative control. Activities of AR and SDH were decreased in heart and kidney of lutein-fed hyperglycemic rats. Also, they had significantly (p < 0.05) decreased malondialdehyde levels (66, 34, and 33 %) and increased reduced glutathione level (81, 18 and 92 %) in serum, heart and kidney, respectively. Altered antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase were also affected in serum, heart and kidney of lutein-fed diabetic group. Lutein prevented cardiac and renal injury in STZ-induced hyperglycemic rats due to potential amelioration of altered activities in polyol pathway and oxidative stress markers.

  15. Effects of Grifola frondosa non-polar bioactive components on high-fat diet fed and streptozotocin-induced hyperglycemic mice.

    Science.gov (United States)

    Shen, Kuo-Ping; Su, Chun-Han; Lu, Tzy-Ming; Lai, Min-Nan; Ng, Lean-Teik

    2015-05-01

    Consumption of medicinal mushrooms for disease prevention and maintaining health has a very long history in Asia. Grifola frondosa (Fr) S.F. Gray (GF) (Meripilaceae) is a medicinal fungus popularly used for enhancing immune systems, lowering blood glucose, and improving spleen, stomach, and nerve functions. This study examines the hypoglycemic effects of GF in vitro and in vivo, and analyzes the chemical profiles of its bioactive components. In vitro hypoglycemic effects of GF was evaluated enzymatically using α-amylase and α-glucosidase inhibition assays, whereas in vivo study was conducted on high-fat diet fed and streptozotocin (HFD + STZ)-induced hyperglycemic mice. GC-MS was used to determine the chemical profiles of bioactive components. The non-polar fraction of GF exhibited a stronger anti-α-glucosidase activity (IC50: 0.0332 mg/ml) than acarbose, but its anti-α-amylase activity (IC50: 0.671 mg/ml) was weaker. Oral administration of GF at 600 mg/kg (GF600) significantly lowered the blood glucose, HbA1c, average blood glucose, and serum total cholesterol levels in hyperglycemic mice. Although GF was found to contain mainly oleic acid and linoleic acid, their levels in the fungus were low, suggesting that the effects of GF on HFD + STZ-induced hyperglycemic mice could be due to factors other than these fatty acids. These results conclude that GF possesses anti-α-glucosidase activity, and hypoglycemic effect in HFD + STZ-induced hyperglycemic mice.

  16. Persistent double dorsal aorta: A systematic review of the literature.

    Science.gov (United States)

    Mills, Brandy; Gest, Thomas

    2017-05-01

    Our discovery of a case of persistent double dorsal aorta prompted us to systematically review the literature of all previously reported cases of this anomaly. For our case, we present a completely separated double dorsal aorta, with the right accessory aorta arising from the abdominal aorta and ascending through the aortic hiatus to supply posterior intercostal arteries (PIAs) to the 9th-3rd spaces bilaterally. We examined and compiled data from the 10 previously reported cases, along with our observations from our cadaver, into a systematic review of all known cases of persistent double dorsal aorta. In addition to our case report and systematic review, we investigated the literature focusing on formation of the dorsal aorta in the embryo in order to postulate potential mechanisms for formation of this anomaly. Two variants of persistent double dorsal aorta have been reported in the literature. The first type is characterized by a double-lumen descending aorta with a central dividing septum, and the second features complete separation of the two dorsal aortae. The completely separated variant shows further heterogeneity in the origins of the PIAs and the iliac arteries, and the majority of the reported cases also demonstrate additional anatomical anomalies. We outline the events in embryonic dorsal aorta formation as well as discuss several potential mechanisms that could underlie persistent double dorsal aorta formation. Clin. Anat. 30:517-524, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Dorsal onlay graft bulbar urethroplasty using buccal mucosa ...

    African Journals Online (AJOL)

    It can be used for penile urethral stricture repair and different types of dorsal onlay graft urethroplasty for bulbar urethral stricture repair. The current paper describes, step by step, Barbagli technique of dorsal onlay graft bulbar urethroplasty using buccal mucosa. The preoperative patient evaluation and postoperative course ...

  18. Peripheral distribution of the human dorsal nerve of the penis.

    Science.gov (United States)

    Yang, C C; Bradley, W E

    1998-06-01

    The integrity of the dorsal nerve of the penis is crucial for normal erectile and ejaculatory function. To our knowledge a description of this nerve along the phallus has not been formally described. We illustrate the distribution of the dorsal nerve of the penis to the penile shaft, anterior urethra and glans. Neuroanatomical dissections were performed on 28 cadaver penis specimens. Electrodiagnostic testing was conducted on 10 healthy male subjects to confirm the anatomical findings. The dorsal nerve of the penis consists of 2 populations of axons, one to innervate the penile shaft and urethra, and the other to innervate the glans. Stimulation of the urethra resulted in responses recorded in the main trunk of the dorsal nerve of the penis and stimulation of the nerve evoked responses within the urethra. Bulbocavernosus muscle contraction was elicited following urethral stimulation. Urethral innervation by the dorsal nerve of the penis supports the view that urethral afferent impulses are a component of reflex ejaculatory activity. The pattern of glanular innervation by the dorsal nerve of the penis identifies the glans as a sensory end organ for sexual reflexes. The undulating character of the dorsal nerve of the penis is a mechanism by which the nerve can accommodate to significant changes in penile length with erection. Electrodiagnostic studies of the dorsal nerve of the penis should be modified to consider the anatomical findings.

  19. The Effect of Near Total Pancreatectomy in Treatment of Hyperinsulinemic Hyperglycemic Infants Children’s Medical Center 2000

    Directory of Open Access Journals (Sweden)

    M Klantary

    2002-09-01

    Full Text Available Background: There are many surgical approaches for hyperinsulinemic hyperglycemic treatment. Subtotal pancreatectomy which has been used for many years, is abounded know due to high recurrence rate, and has been replaced by near total resection. This study focuses on “near total resection”. Materials and Mehods: In this study 15 cases of hyper insulinemic hyperglycemia patients which has been operated since year 1985 till 2000 in the Childrens Medical Center, has brought into consideration and described as a case series study. Results: From the patients, three cases were operated by subtotal pancreatomy and all of them have had recurrence. In the remaining twelve cases, the method used was different and “near subtotal pancreatomy” were used. The recurrence rate in this group was zero and there were not also any case of sepsis. Postoperative complications were rather low and the most common postoperative finding in these patients was transient hypoglycemia. Conclusion: Near total pancreatomy for hyperinsulinemic hypoglycemia which is implemented by an expert surgeon with low complication and high cure rate, can be considered as a safe technique with high cure rate and satisfactory results.

  20. File list: ALL.Lar.10.AllAg.Dorsal_mesothoracic_disc [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: ALL.Lar.50.AllAg.Dorsal_mesothoracic_disc [Chip-atlas[Archive

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  8. Dorsal ulnar cutaneous nerve conduction: reference values

    Directory of Open Access Journals (Sweden)

    Garibaldi Solange G.

    2002-01-01

    Full Text Available We investigated the reference values of the dorsal ulnar cutaneous nerve (DUC sensory nerve conduction (SNC in 66 healthy individuals. Measurements were processed using stimulating electrodes positioned between the ulnar bone and the flexor carpi ulnaris muscle, 11-13 cm proximal to the active electrode recording. Superficial recording electrodes were placed on the fourth intermetacarpal space. The mean sensory conduction velocity (SCV in males was 63.7 -- 0.16 x age ± 3.36 m/s and in females was 57.7 ± 3.37 m/s. The mean sensory nerve action potential (SNAP amplitude in males was 19.5 ± 10.7 µV and in females was 24.6 ± 5.8 µV. The mean SNAP duration was 0.96 ± 0.13 ms. No significant differences regarding the DUC-SCV, distal latency, and SNAP duration or amplitude were found between both sides of the same subject. The amplitude of the SNAP was higher in females than males. The effects of age on DUC-SCV were distinct for each gender.

  9. Event related potentials recorded in Dorsal Simultanagnosia.

    Science.gov (United States)

    Onofrj, M; Fulgente, T; Thomas, A

    1995-12-01

    Visual evoked potentials (VEPs) to central and lateral half field patterned stimuli of 1, 2 and 4 cycles per degree (cpd) were recorded in a patient with Dorsal Simultanagnosia due to bilateral lesions of parieto-occipital junction. VEPs consisted of the normal N1-P1-N2 components with same spatial frequency sensitivity as in controls. VEPs had similar latencies and amplitudes whether the patient could see or not the patterned stimuli. Event related potentials (ERPs) to visual and acoustic odd-ball paradigm were also recorded in the same patient. Visual ERPs consisted of an early NA-effect, and of N2-P3 components. P3 was recorded only from frontal, central and temporal derivations. The topographical P3 abnormality was, however, the same for visual and acoustic odd-ball paradigms. The amplitude of P3 was smaller when the patient missed visual stimuli. These findings show that severe bilateral lesions at the parieto-occipital junction, inducing Simultanagnosia, do not obliterate VEPs or ERPs components.

  10. Identification and mechanism of regulation of the zebrafish dorsal determinant.

    Science.gov (United States)

    Lu, Fu-I; Thisse, Christine; Thisse, Bernard

    2011-09-20

    In vertebrates, the animal-vegetal axis is determined during oogenesis and at ovulation, the egg is radially symmetric. In anamniotes, following fertilization, a microtubule-dependent movement leads to the displacement of maternal dorsal determinants from the vegetal pole to the future dorsal side of the embryo, providing the initial breaking of radial symmetry [Weaver C, Kimelman D (2004) Development 131:3491-3499]. These dorsal determinants induce β-catenin nuclear translocation in dorsal cells of the blastula. Previous work in amphibians has shown that secreted Wnt11/5a complexes, regulated by the Wnt antagonist Dkk-1, are required for the initiation of embryonic axis formation [Cha et al. (2009) Curr Biol 29:1573-1580]. In the current study, we determined that the vegetal maternal dorsal determinant in fish is not the Wnt11/5a complex but the canonical Wnt, Wnt8a. Translation of this mRNA and secretion of the Wnt8a protein result in a dorsal-to-ventral gradient of Wnt stimulation, extending across the entire embryo. This gradient is counterbalanced by two Wnt inhibitors, Sfrp1a and Frzb. These proteins are essential to restrict the activation of the canonical Wnt pathway to the dorsal marginal blastomeres by defining the domain where the Wnt8a activity gradient is above the threshold value necessary for triggering the canonical β-catenin pathway. In summary, this study establishes that the zebrafish maternal dorsal determinant, Wnt8a, is required to localize the primary dorsal center, and that the extent of this domain is defined by the activity of two maternally provided Wnt antagonists, Sfrp1a and Frzb.

  11. Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats.

    Science.gov (United States)

    Baba, Hiroshi; Petrenko, Andrey B; Fujiwara, Naoshi

    2016-10-01

    Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δ-1 subunits of voltage-gated calcium (Ca(2+)) channels. However, the exact analgesic mechanism after its binding to α2δ-1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (≈10μM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca(2+)-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca(2+) signals predominantly in the superficial dorsal horn. Clinically relevant (10μM) and a very high concentration of pregabalin (100μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca(2+) signals, whereas an extremely high dose of pregabalin (300μM) slightly but significantly attenuated Ca(2+) signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Increased risk of ischemic stroke after hyperosmolar hyperglycemic state: a population-based follow-up study.

    Directory of Open Access Journals (Sweden)

    Jen-Yu Wang

    Full Text Available BACKGROUND: Although much attention has been focused on the association between chronic hyperglycemia and cerebrovascular diseases in type 2 diabetes mellitus (DM patients, there is no data regarding the risk of ischemic stroke after a hyperosmolar hyperglycemic state (HHS attack. The objective of this study was to investigate the risk of ischemic stroke in type 2 DM patients after an HHS attack. METHODS: From 2004 to 2008, this retrospective observational study was conducted on a large cohort of Taiwanese using Taiwan's National Health Insurance Research Database (NHIRD. We identified 19,031 type 2 DM patients who were discharged with a diagnosis of HHS and 521,229 type 2 DM patients without an HHS diagnosis. Using the propensity score generated from logistic regression models, conditional on baseline covariates, we matched 19,031 type 2 DM patients with an HHS diagnosis with the same number from the comparison cohort. The one-year cumulative rate for ischemic stroke was estimated using the Kaplan-Meier method. After adjusting covariates, Cox proportional hazard regression was used to compute the adjusted one-year rate of ischemic stroke. RESULTS: Of the patients sampled, 1,810 (9.5% of the type 2 DM patients with HHS and 996 (5.2% of the comparison cohort developed ischemic stroke during the one-year follow-up period. After adjusting for covariates, the adjusted HR for developing ischemic stroke during the one-year follow-up period was 1.8 (95% C.I., 1.67 to 1.95, P<0.001 for type 2 DM patients with HHS compared with those without HHS. CONCLUSION: Although DM is a well-recognized risk factor for atherosclerosis, type 2 DM patients that have suffered a HHS attacks are at an increased risk of developing ischemic stroke compared with those without HHS.

  13. SPINAL DEFORMITIES AFTER SELECTIVE DORSAL RHIZOTOMY

    Directory of Open Access Journals (Sweden)

    PATRICIO PABLO MANZONE

    Full Text Available ABSTRACT Objective: Selective dorsal rhizotomy (SDR used for spasticity treatment could worsen or develop spinal deformities. Our goal is to describe spinal deformities seen in patients with cerebral palsy (CP after being treated by SDR. Methods: Retrospective study of patients operated on (SDR between January/1999 and June/2012. Inclusion criteria: spinal Rx before SDR surgery, spinography, and assessment at follow-up. We evaluated several factors emphasizing level and type of SDR approach, spinal deformity and its treatment, final Risser, and follow-up duration. Results: We found 7 patients (6 males: mean age at SDR 7.56 years (4.08-11.16. Mean follow-up: 6.64 years (2.16-13, final age: 14.32 years (7.5-19. No patient had previous deformity. GMFCS: 2 patients level IV, 2 level III, 3 level II. Initial walking status: 2 community walkers, 2 household walkers, 2 functional walkers, 1 not ambulant, at the follow-up, 3 patients improved, and 4 kept their status. We found 4 TL/L laminotomies, 2 L/LS laminectomies, and 1 thoracic laminectomy. Six spinal deformities were observed: 2 sagittal, 3 mixed, and 1 scoliosis. There was no association among the type of deformity, final gait status, topographic type, GMFCS, age, or SDR approach. Three patients had surgery indication for spinal deformity at skeletal maturity, while those patients with smaller deformities were still immature (Risser 0 to 2/3 although with progressive curves. Conclusions: After SDR, patients should be periodically evaluated until they reach Risser 5. The development of a deformity does not compromise functional results but adds morbidity because it may require surgical treatment.

  14. Neurogenic contraction and relaxation of human penile deep dorsal vein

    OpenAIRE

    Segarra, Gloria; Medina, Pascual; Domenech, Cristina; Martínez León, Juan B; Vila, José M.; Aldasoro, Martin; Lluch, Salvador

    1998-01-01

    The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin.Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant respon...

  15. [Dorsal capsulodesis for the treatment of scapholunate instability].

    Science.gov (United States)

    Stephan, Christine; Prommersberger, Karl-Josef; van Schoonhoven, Jörg

    2009-11-01

    To regain stability of the proximal carpal row after scapholunate ligament rupture in order to avoid osteoarthritis and carpal collapse. As additional therapy in scapholunate ligament repair especially in patients with static, but reducible scapholunate malalignment. Fixed scapholunate malalignment. Osteoarthritis of the radiocarpal or the midcarpal joint. Dorsal approach to the carpal joint with release of the second, third and fourth extensor compartment and resection of the dorsal interosseous nerve. Opening of the radiocarpal joint for inspection of the chondral surfaces and the scapholunate ligament for possible repair. If needed, reduction of scaphoid and lunate. Repair of the scapholunate ligament. If a reduction of scaphoid and lunate is necessary, temporary Kirschner wire fixation of the scaphoid to the capitate and the lunate. The dorsal intercarpal ligament is identified and its middle third is dissected and elevated from the triquetrum remaining attached to the distal scaphoid pole. The ulnar end of the elevated part of the dorsal intercarpal ligament is pulled through a split in the dorsal radiotriquetral ligament and fixed to itself. Closure of the proximal and distal third of the dorsal intercarpal ligament. Management Immobilization in a below-elbow cast including the metacarpophalangeal joint of the thumb for 6 weeks. Removal of the Kirschner wires, if used, 8 weeks postoperatively. Physiotherapy to improve wrist motion. Most of the reports in the literature show an improvement of pain. The effect on radiologic parameters and the development of osteoarthritis remains uncertain.

  16. Functional connectivity of the dorsal striatum in female musicians

    Directory of Open Access Journals (Sweden)

    Shoji eTanaka

    2016-04-01

    Full Text Available The dorsal striatum (caudate/putamen is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians.Resting state functional magnetic resonance imaging (fMRI data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to graph theoretical analysis and functional connectivity analysis. The graph theoretical analysis of the entire brain revealed that the degree, which represents the number of connections, of the bilateral putamen was significantly lower in musicians than in nonmusicians. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum and between the left caudate nucleus and cerebellum. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum, with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers. To the best of our knowledge, this is the first study suggesting that long-term musical training results in a less extensive or selective functional network of the dorsal striatum.

  17. Functional Connectivity of the Dorsal Striatum in Female Musicians.

    Science.gov (United States)

    Tanaka, Shoji; Kirino, Eiji

    2016-01-01

    The dorsal striatum (caudate/putamen) is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC) motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians. Resting state functional magnetic resonance imaging (fMRI) data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to functional connectivity analysis and graph theoretical analysis. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum (FO) and between the left caudate nucleus and cerebellum. The graph theoretical analysis of the entire brain revealed that the degrees, which represent the numbers of connections, of the bilateral putamen were significantly lower in musicians than in nonmusicians. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers, suggesting that long-term musical training reshapes the functional network of the dorsal striatum to be less extensive or selective.

  18. Seedling root targets

    Science.gov (United States)

    Diane L. Haase

    2011-01-01

    Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

  19. Different effects of two dipeptidyl peptidase-4 inhibitors and glimepiride on β-cell function in a newly designed two-step hyperglycemic clamp.

    Science.gov (United States)

    Zhang, Yifei; Chi, Jie; Wang, Weiqing; Hong, Jie; Gu, Weiqiong; Wang, Bokai; Ning, Guang

    2015-03-01

    Dipeptidyl peptidase (DPP)-4 inhibitors and sulfonylureas may have different effects on islet function. We designed a new two-step hyperglycemic clamp to further compare the effects of sitagliptin, saxagliptin, and glimepiride on β-cell function and the incretin effect. The present study was a four-way cross-over open label randomized study. Twelve healthy male subjects were administered a single dose of sitagliptin (100 mg), saxagliptin (5 mg), glimepiride (2 mg) or blank control 2 h before undergoing a two-step hyperglycemic clamp (Step 1: only intravenous glucose was administered; Step 2: i.v. glucose loading was combined with oral glucose consumption). Two-phase insulin secretion, glucagon secretion, and incretin levels were measured during the clamp. In Step 1, with i.v. glucose only, there were no differences between the effects of the three drugs on insulin secretion, except that saxagliptin increased second-phase insulin secretion more than glimepiride (P = 0.007). In Step 2, oral glucose consumption led to an approximate two fold increase in insulin secretion and both gliptins significantly increased first-phase insulin secretion compared with glimepiride (P = 0.003 for both). Saxagliptin further increased second-phase insulin secretion compared with glimepiride (P = 0.005) and sitagliptin (P Step 2. The two-step hyperglycemic clamp appears to be a precise method to assess β-cell function by taking the effect of incretins into consideration. The oral glucose consumption adds to the i.v. glucose infusion, amplifying the differences in the effects of DPP-4 inhibitors and glimepiride on insulin secretion. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  20. Correlations between neuronal morphology and electrophysiological features in the rodent superficial dorsal horn

    Science.gov (United States)

    Grudt, T J; Perl, E R

    2002-01-01

    Relationships between the morphology of individual neurones of the spinal superficial dorsal horn (SDH), laminae I and II, and their electrophysiological properties were studied in spinal cord slices prepared from anaesthetized, free-ranging hamsters. Tight-seal, whole-cell recordings were made with pipette microelectrodes filled with biocytin to establish electrophysiological characteristics and to label the studied neurones. Neurones were categorized according to location and size of the somata, the dendritic and axonal pattern of arborization, spontaneous synaptic potentials, evoked postsynaptic currents, pattern of discharge to depolarizing pulses and current-voltage relationships. Data were obtained for 170 neurones; 13 of these had somata in lamina I and 157 in lamina II. Stimulation of the segmental dorsal root evoked a prompt excitatory response in almost every neurone sampled (161/166) with nearly 3/4 displaying putative monosynaptic EPSCs. The majority of neurones (133/170) fitted one of several distinctive morphological categories. To a considerable extent, neurones with a common morphological configuration and neurite disposition shared electrophysiological characteristics. Five of the 13 lamina I neurones were relatively large with extensive dendritic arborization in the horizontal dimension and a prominent axon directed ventrally and contralaterally. These presumptive ventrolateral projection neurones differed structurally and electrophysiologically from the other lamina I neurones, which had ipsilateral, locally arborizing axons and/or branches entering the dorsal lateral funiculus. One hundred and twenty lamina II neurones fitted one of five morphological categories: islet, central, medial-lateral, radial or vertical. Central cells were further divided into three groups on functional features. We conclude that the spinal SDH comprises many types of neurones whose morphological characteristics are associated with specific functional features implying

  1. Sialic acid accelerates the electrophoretic velocity of injured dorsal root ganglion neurons.

    Science.gov (United States)

    Li, Chen-Xu; Ma, Guo-Ying; Guo, Min-Fang; Liu, Ying

    2015-06-01

    Peripheral nerve injury has been shown to result in ectopic spontaneous discharges on soma and injured sites of sensory neurons, thereby inducing neuropathic pain. With the increase of membrane proteins on soma and injured site neurons, the negatively charged sialic acids bind to the external domains of membrane proteins, resulting in an increase of this charge. We therefore speculate that the electrophoretic velocity of injured neurons may be faster than non-injured neurons. The present study established rat models of neuropathic pain via chronic constriction injury. Results of the cell electrophoresis test revealed that the electrophoretic velocity of injured neuronal cells was faster than that of non-injured (control) cells. We then treated cells with divalent cations of Ca(2+) and organic compounds with positive charges, polylysine to counteract the negatively charged sialic acids, or neuraminidase to specifically remove sialic acids from the membrane surface of injured neurons. All three treatments significantly reduced the electrophoretic velocity of injured neuronal cells. These findings suggest that enhanced sialic acids on injured neurons may accelerate the electrophoretic velocity of injured neurons.

  2. Sialic acid accelerates the electrophoretic velocity of injured dorsal root ganglion neurons

    National Research Council Canada - National Science Library

    Chen-xu Li Guo-ying Ma Min-fang Guo Ying Liu

    2015-01-01

    .... With the increase of membrane proteins on soma and injured site neurons, the negatively charged sialic acids bind to the external domains of membrane proteins, resulting in an increase of this charge...

  3. Sialic acid accelerates the electrophoretic velocity of injured dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Chen-xu Li

    2015-01-01

    Full Text Available Peripheral nerve injury has been shown to result in ectopic spontaneous discharges on soma and injured sites of sensory neurons, thereby inducing neuropathic pain. With the increase of membrane proteins on soma and injured site neurons, the negatively charged sialic acids bind to the external domains of membrane proteins, resulting in an increase of this charge. We therefore speculate that the electrophoretic velocity of injured neurons may be faster than non-injured neurons. The present study established rat models of neuropathic pain via chronic constriction injury. Results of the cell electrophoresis test revealed that the electrophoretic velocity of injured neuronal cells was faster than that of non-injured (control cells. We then treated cells with divalent cations of Ca 2+ and organic compounds with positive charges, polylysine to counteract the negatively charged sialic acids, or neuraminidase to specifically remove sialic acids from the membrane surface of injured neurons. All three treatments significantly reduced the electrophoretic velocity of injured neuronal cells. These findings suggest that enhanced sialic acids on injured neurons may accelerate the electrophoretic velocity of injured neurons.

  4. Sialic acid accelerates the electrophoretic velocity of injured dorsal root ganglion neurons

    OpenAIRE

    Chen-xu Li; Guo-ying Ma; Min-fang Guo; Ying Liu

    2015-01-01

    Peripheral nerve injury has been shown to result in ectopic spontaneous discharges on soma and injured sites of sensory neurons, thereby inducing neuropathic pain. With the increase of membrane proteins on soma and injured site neurons, the negatively charged sialic acids bind to the external domains of membrane proteins, resulting in an increase of this charge. We therefore speculate that the electrophoretic velocity of injured neurons may be faster than non-injured neurons. The present stud...

  5. Modulators of calcium influx regulate membrane excitability in rat dorsal root ganglion neurons

    NARCIS (Netherlands)

    Lirk, Philipp; Poroli, Mark; Rigaud, Marcel; Fuchs, Andreas; Fillip, Patrick; Huang, Chun-Yuan; Ljubkovic, Marko; Sapunar, Damir; Hogan, Quinn

    2008-01-01

    Chronic neuropathic pain resulting from neuronal damage remains difficult to treat, in part, because of incomplete understanding of underlying cellular mechanisms. We have previously shown that inward Ca2+ flux (I(Ca)) across the sensory neuron plasmalemma is decreased in a rodent model of chronic

  6. Parvalbumin and TRPV1 receptor expression in dorsal root ganglion neurons after acute peripheral inflammation

    Czech Academy of Sciences Publication Activity Database

    Zachařová, Gisela; Paleček, Jiří

    2009-01-01

    Roč. 58, č. 2 (2009), s. 305-309 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/06/1115; GA ČR(CZ) GA305/09/1228; GA ČR(CZ) GA304/08/0256; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : pain * arthritis * DRG Subject RIV: FH - Neurology Impact factor: 1.430, year: 2009

  7. Correlation of the electrophysiological profiles and sodium channel transcripts of individual rat dorsal root ganglia neurons

    Science.gov (United States)

    Thériault, Olivier; Chahine, Mohamed

    2014-01-01

    Voltage gated sodium channels (Nav channels) play an important role in nociceptive transmission. They are intimately tied to the genesis and transmission of neuronal firing. Five different isoforms (Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) have been linked to nociceptive responses. A change in the biophysical properties of these channels or in their expression levels occurs in different pathological pain states. However, the precise involvement of the isoforms in the genesis and transmission of nociceptive responses is unknown. The aim of the present study was to investigate the synergy between the different populations of Nav channels that give individual neurons a unique electrophysical profile. We used the patch-clamp technique in the whole-cell configuration to record Nav currents and action potentials from acutely dissociated small diameter DRG neurons (<30 μm) from adult rats. We also performed single cell qPCR on the same neurons. Our results revealed that there is a strong correlation between Nav currents and mRNA transcripts in individual neurons. A cluster analysis showed that subgroups formed by Nav channel transcripts by mRNA quantification have different biophysical properties. In addition, the firing frequency of the neurons was not affected by the relative populations of Nav channel. The synergy between populations of Nav channel in individual small diameter DRG neurons gives each neuron a unique electrophysiological profile. The Nav channel remodeling that occurs in different pathological pain states may be responsible for the sensitization of the neurons. PMID:25285069

  8. Spinal Cord Stimulation of the Dorsal Root Ganglion for Groin Pain-A Retrospective Review

    NARCIS (Netherlands)

    Schu, S. (Stefan); Gulve, A. (Ashish); Eldabe, S. (Sam); Baranidharan, G. (Ganesan); Wolf, K. (Katharina); Demmel, W. (Walter); Rasche, D. (Dirk); Sharma, M. (Manohar); Klase, D. (Daniel); Jahnichen, G. (Gunnar); Wahlstedt, A. (Anders); Nijhuis, H. (Harold); A.L. Liem (Liong)

    2015-01-01

    textabstractBackground: Spinal cord stimulation (SCS) is a standard treatment option for chronic neuropathic pain. However, some anatomical pain distributions are known to be difficult to cover with traditional SCS-induced paresthesias and/or may also induce additional, unwanted stimulation. We

  9. Correlation of the electrophysiological profiles and sodium channel transcripts of individual rat dorsal root ganglia neurons

    Directory of Open Access Journals (Sweden)

    Olivier eTheriault

    2014-09-01

    Full Text Available Voltage gated sodium channels (Na+ channels play an important role in nociceptive transmission. They are intimately tied to the genesis and transmission of neuronal firing. Five different isoforms (Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9 have been linked to nociceptive responses. A change in the biophysical properties of these channels or in their expression levels occurs in different pathological pain states. However, the precise involvement of the isoforms in the genesis and transmission of nociceptive responses is unknown. The aim of the present study was to investigate the synergy between the different populations Na+ channels that give individual neurons a unique electrophysical profile.We used the patch-clamp technique in the whole-cell configuration to record Na+ currents and action potentials from acutely dissociated small diameter DRG neurons (<30 µM from adult rats. We also performed single cell qPCR on the same neurons. Our results revealed that there is a strong correlation between Na+ currents and mRNA transcripts in individual neurons. A cluster analysis showed that subgroups formed by Na+ channel transcripts by mRNA quantification have different biophysical properties. In addition, the firing frequency of the neurons was not affected by the relative populations of Na+ channel. The synergy between populations of Na+ channel in individual small diameter DRG neurons gives each neuron a unique electrophysiological profile. The Na+ channel remodeling that occurs in different pathological pain states may be responsible for the sensitization of the neurons.

  10. Microanatomy of the brachial plexus roots and its clinical significance.

    Science.gov (United States)

    Zhong, Li-Yuan; Wang, Ai-Ping; Hong, Li; Chen, Sheng-Hua; Wang, Xian-Qin; Lv, Yun-Cheng; Peng, Tian-Hong

    2017-06-01

    To provide the anatomical basis of brachial plexus roots for the diagnosis and treatment of brachial plexus root avulsion injury. The morphological features of brachial plexus roots were observed and measured on 15 cervicothoracic spine of adult cadavers. The relationship of brachial plexus nerve roots and the surrounding tissues also were observed, as well as the blood supply of anterior and posterior roots of the brachial plexus. Origination of the nerve roots in the dorsal-ventral direction from the midline was fine-tuned at each level along the spinal cord. The minimum distance of the origin of the nerve root to midline was 2.2 mm at C 5, while the maximum was 3.1 mm at T 1. Inversely, the distance between the origin of the posterior root and the midline of the spinal cord gradually decreased, the maximum being 4.2 mm at C 5 and minimum 2.7 mm at T 1. Meanwhile, there was complicated fibrous connection among posterior roots of the brachial plexus. The C 5-6 nerve roots interlaced with tendons of the scalenus anterior and scalenus medius and fused with the transverse-radicular ligaments in the intervertebral foramina. However, these ligaments were not seen in C 7-8, and T 1. The blood supply of the anterior and posterior roots of the brachial plexus was from the segmental branches of the vertebral artery, deep cervical artery and ascending cervical artery, with a mean outer diameter of 0.61 mm. The systematic and comprehensive anatomic data of the brachial plexus roots provides the anatomical basis to diagnose and treat the brachial plexus root avulsion injury.

  11. Hyperosmolar nonketotic hyperglycemic coma induced by methylprednisolone pulse therapy for acute rejection after liver transplantation: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Zhou J

    2014-12-01

    Full Text Available Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC is a serious, rare complication induced by methylprednisolone (MP pulse therapy for acute rejection after orthotopic liver transplantation (OLT. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment

  12. Rapid Non-Enzymatic Glycation of the Insulin Receptor under Hyperglycemic Conditions Inhibits Insulin Binding In Vitro: Implications for Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Tyler Rhinesmith

    2017-12-01

    Full Text Available The causes of insulin resistance are not well-understood in either type 1 or type 2 diabetes. Insulin (INS is known to undergo rapid non-enzymatic covalent conjugation to glucose or other sugars (glycation. Because the insulin receptor (IR has INS-like regions associated with both glucose and INS binding, we hypothesize that hyperglycemic conditions may rapidly glycate the IR, chronically interfering with INS binding. IR peptides were synthesized spanning IR- associated INS-binding regions. Glycation rates of peptides under hyperglycemic conditions were followed over six days using matrix assisted laser desorption/ionization-time of flight (MALDI-TOF mass spectrometry. INS conjugated to horse-radish peroxidase was used to determine INS binding to IR peptides in glycated and non-glycated forms. Several IR peptides were glycated up to 14% within days of exposure to 20–60 mM glucose. Rates of IR-peptide glycation were comparable to those of insulin. Glycation of four IR peptides significantly inhibits INS binding to them. Glycation of intact IR also decreases INS binding by about a third, although it was not possible to confirm the glycation sites on the intact IR. Glycation of the IR may therefore provide a mechanism by which INS resistance develops in diabetes. Demonstration of glycation of intact IR in vivo is needed.

  13. Dorsal and ventral language pathways in persistent developmental stuttering.

    Science.gov (United States)

    Kronfeld-Duenias, Vered; Amir, Ofer; Ezrati-Vinacour, Ruth; Civier, Oren; Ben-Shachar, Michal

    2016-08-01

    Persistent developmental stuttering is a speech disorder that affects an individual's ability to fluently produce speech. While the disorder mainly manifests in situations that require language production, it is still unclear whether persistent developmental stuttering is indeed a language impairment, and if so, which language stream is implicated in people who stutter. In this study, we take a neuroanatomical approach to this question by examining the structural properties of the dorsal and ventral language pathways in adults who stutter (AWS) and fluent controls. We use diffusion magnetic resonance imaging and individualized tract identification to extract white matter volumes and diffusion properties of these tracts in samples of adults who do and do not stutter. We further quantify diffusion properties at multiple points along the tract and examine group differences within these diffusivity profiles. Our results show differences in the dorsal, but not in the ventral, language-related tracts. Specifically, AWS show reduced volume of the left dorsal stream, as well as lower anisotropy in the right dorsal stream. These data provide neuroanatomical support for the view that stuttering involves an impairment in the bidirectional mapping between auditory and articulatory cortices supported by the dorsal pathways, not in lexical access and semantic aspects of language processing which are thought to rely more heavily on the left ventral pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Structural and molecular alterations of primary afferent fibres in the spinal dorsal horn in vincristine-induced neuropathy in rat.

    Science.gov (United States)

    Thibault, Karine; Rivals, Isabelle; M'Dahoma, Saïd; Dubacq, Sophie; Pezet, Sophie; Calvino, Bernard

    2013-11-01

    Vincristine is one of the most common anti-cancer drug therapies administered for the treatment of many types of cancer. Its dose-limiting side effect is the emergence of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. This study sought to understand the mechanisms underlying the development of neuropathic pain by vincristine-induced neurotoxicity. We focused on signs of functional changes and revealed that deep layers of the spinal cord (III-IV) experience increased neuronal activity both in the absence of peripheral stimulation and, as a result of tactile mechanical stimulations. These laminae and superficial laminae I-II were also subject to structural changes as evidenced by an increase in immunoreactivity of Piccolo, a marker of active presynaptic elements. Further investigations performed, using DNA microarray technology, describe a large number of genes differentially expressed in dorsal root ganglions and in the spinal dorsal horn after vincristine treatment. Our study describes an important list of genes differentially regulated by vincristine treatment that will be useful for future studies and brings forward evidence for molecular and anatomical modifications of large diameter sensory neurons terminating in deep dorsal horn laminae, which could participate in the development of tactile allodynia.

  15. ROOT Reference Documentation

    CERN Document Server

    Fuakye, Eric Gyabeng

    2017-01-01

    A ROOT Reference Documentation has been implemented to generate all the lists of libraries needed for each ROOT class. Doxygen has no option to generate or add the lists of libraries for each ROOT class. Therefore shell scripting and a basic C++ program was employed to import the lists of libraries needed by each ROOT class.

  16. The Dorsal Attentional System in Oculomotor Learning of Predictive Information

    Directory of Open Access Journals (Sweden)

    Philip eTseng

    2013-08-01

    Full Text Available The dorsal attentional network is known for its role in directing top-down visual attention towards task-relevant stimuli. This goal-directed nature of the dorsal network makes it a suitable candidate for processing and extracting predictive information from the visual environment. In this mini review we briefly summarize some of the findings that delineate the neural substrates that contribute to predictive learning at both levels within the dorsal attentional system: including the frontal eye field and posterior parietal cortex. We also discuss the similarities and differences between these two regions when it comes to learning predictive information. The current findings from the literature suggest that the frontal eye fields may be more involved in top-down spatial attention, whereas the parietal cortex is involved in processing task-relevant attentional influences driven by stimulus salience, both contribute to the processing of predictive cues at different time points.

  17. Dorsal eye selector pannier (pnr) suppresses the eye fate to define dorsal margin of the Drosophila eye

    Science.gov (United States)

    Oros, Sarah M.; Tare, Meghana; Kango-Singh, Madhuri; Singh, Amit

    2010-01-01

    Axial patterning is crucial for organogenesis. During Drosophila eye development, dorso-ventral (DV) axis determination is the first lineage restriction event. The eye primordium begins with a default ventral fate, on which the dorsal eye fate is established by expression of the GATA-1 transcription factor pannier (pnr). Earlier, it was suggested that loss of pnr function induces enlargement in the dorsal eye due to ectopic equator formation. Interestingly, we found that in addition to regulating DV patterning, pnr suppresses the eye fate by downregulating the core retinal determination genes eyes absent (eya), sine oculis (so) and dacshund (dac) to define the dorsal eye margin. We found that pnr acts downstream of Ey and affect the retinal determination pathway by suppressing eya. Further analysis of the “eye suppression” function of pnr revealed that this function is likely mediated through suppression of the homeotic gene teashirt (tsh) and is independent of homothorax (hth), a negative regulator of eye. Pnr expression is restricted to the peripodial membrane on the dorsal eye margin, which gives rise to head structures around the eye, and pnr is not expressed in the eye disc proper that forms the retina. Thus, pnr has dual function, during early developmental stages pnr is involved in axial patterning whereas later it promotes the head specific fate. These studies will help in understanding the developmental regulation of boundary formation of the eye field on the dorsal eye margin. PMID:20691679

  18. Surgical Strategy and Techniques for Low-Profile Dorsal Plating in Treating Dorsally Displaced Unstable Distal Radius Fractures.

    Science.gov (United States)

    Hamada, Yoshitaka; Gotani, Hiroyuki; Hibino, Naohito; Tanaka, Yoshitaka; Satoh, Ryousuke; Sasaki, Kousuke; Kanchanathepsak, Thepparat

    2017-05-01

    Background The low-profile dorsal locking plating (DLP) technique is useful for treating dorsally comminuted intra-articular distal radius fractures; however, due to the complications associated with DLP, the technique is not widely used. Methods A retrospective review of 24 consecutive cases treated with DLP were done. Results All cases were classified into two types by surgical strategy according to the fracture pattern. In type 1, there is a volar fracture line distal to the watershed line in the dorsally displaced fragment, and this type is treated by H-framed DLP. In type 2, the displaced dorsal die-punch fragment is associated with a minimally displaced styloid shearing fracture or a transverse volar fracture line. We found that the die-punch fragment was reduced by the buttress effect of small l-shaped DLP after stabilization of the styloid shearing for the volar segment by cannulated screws from radial styloid processes. At 6 months after surgery, outcomes were good or excellent based on the modified Mayo wrist scores with no serious complications except one case. The mean range of motion of each type was as follows: the palmar flexion was 50, 65 degrees, dorsiflexion was 70, 75 degrees, supination was 85, 85 degrees, and pronation was 80, 80 degrees; in type 1 and 2, respectively. Conclusion DLP is a useful technique for the treatment of selected cases of dorsally displaced, comminuted intra-articular fractures of the distal radius with careful soft tissue coverage.

  19. [The dorsal nerve of the clitoris: surgical applications].

    Science.gov (United States)

    Balaya, V; Aubin, A; Rogez, J-M; Douard, R; Delmas, V

    2014-03-01

    To describe the course of the dorsal nerve of the clitoris (DNC) to better define its anatomy in the human adult and to help surgeons to avoid iatrogenic injury during surgical procedures. An extensive review of the current literature was done on Medline via PubMed by using the following keywords: "anatomie du clitoris", "anatomy of clitoris", "nerf dorsal du clitoris", "dorsal nerve of clitoris", "réparation clitoridienne", "transposition clitoridienne", "surgery of the clitoris", "clitoridoplasty". This review analyzed dissection, magnetic resonance imaging, 3-dimensional sectional anatomy reconstruction and immuno-histochemical studies. The DNC comes from the pudendal nerve. He travels from under the inferior pubis ramus to the posterosuperior edge of the clitoral crus. The DNC reappears under the pubic symphysis and enters the deep component of the suspensory ligament. He runs on the dorsal face of the clitoral body at 11 and 1 o'clock. Distally, he gives many nervous ramifications, runs along the tunica and enters the glans. The NDC might be surgically injured (i) under the pubic symphysis, at the union of the two crus of clitoris and (ii) on the dorsal surface of the clitoral body. The pathway of the DNC on the dorsal face of the clitoris permits to approach the ventral face of the clitoris without risk of iatrogenic injuries. The distance between the pubic symphysis and the DNC implies that the incision should be done just under the pubic symphysis. Distally, the dissection of the DNC next the glands appears as dangerous and impossible, considering that the DNC is too close to the glandular tissues. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Agenesis of the dorsal mesentery presenting in an adolescent

    Directory of Open Access Journals (Sweden)

    Anith Chacko

    2013-03-01

    Full Text Available Agenesis of the dorsal mesentery is a rare occurrence that usually presents in children. It is associated with proximal small bowel malrotation as well as high jejunal atresia with discontinuity of the small bowel. We present a case report of an adolescent presenting with clinical features of proximal small bowel obstruction (confirmed on imaging as well as acute pancreatitis. At laparotomy, he was found to have no dorsal mesentery, without small bowel atresia, and the duodenum was fixed to the posterior abdominal wall. The patient recovered well and remained symptom-free.

  1. Dorsal approach for open reduction of complex metacarpophalangeal joint dislocations.

    Science.gov (United States)

    Patterson, Ryan W; Maschke, Steven D; Evans, Peter J; Lawton, Jeffrey N

    2008-11-01

    The metacarpophalangeal (MP) joint is resistant to injury due to its strong capsuloligamentous structures, which include the volar plate and deep transverse metacarpal and collateral ligaments. Complex MP joint dislocations are, by definition, irreducible by closed means and require open reduction, as the volar plate becomes entrapped between the metacarpal head and proximal phalanx. The dorsal approach may offer the following advantages: 1) reduced risk to palmarly displaced neurovascular structures, 2) facilitated management of osteochondral fractures, and 3) full exposure of the volar plate. However, the dorsal approach requires splitting of the volar plate for adequate reduction, which may delay recovery.

  2. Percutaneous fixation of selected scaphoid fractures by dorsal approach

    OpenAIRE

    Naranje, Sameer; Kotwal, P. P.; Shamshery, P.; Gupta, Vikas; Nag, H. L.

    2009-01-01

    The aim of our study was to evaluate clinical, radiological and functional outcomes of selected cases of percutaneous fixation of scaphoid fractures via a dorsal approach. Percutaneous fixation by dorsal approach was done in 32 patients (mean age 32.2 years) involving both fresh and late scaphoid fracture presentations (mean 17 days). Fourteen cases of B1 type, ten cases of B2 and eight cases of C type (Herbert’s classification) were treated. The patients were prospectively followed up clinic...

  3. Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn

    Directory of Open Access Journals (Sweden)

    Black Joel A

    2012-11-01

    Full Text Available Abstract Background Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7 has been implicated as playing a critical role in pain pathways, we examined by immunocytochemical methods the expression and distribution of Nav1.7 in rat dorsal root ganglia neurons, from peripheral terminals in the skin to central terminals in the spinal cord dorsal horn. Results Nav1.7 is robustly expressed within the somata of peptidergic and non-peptidergic DRG neurons, and along the peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also expressed at nodes of Ranvier in a subpopulation of Aδ-fibers within sciatic nerve and dorsal root. The peripheral terminals of DRG neurons within skin, intraepidermal nerve fibers (IENF, exhibit robust Nav1.7 immunolabeling. The central projections of DRG neurons in the superficial lamina of spinal cord dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic terminals. Conclusions The expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to preterminal central branches and terminals in the dorsal horn. These data support a major contribution for Nav1.7 in pain pathways, including action potential electrogenesis, conduction along axonal trunks and depolarization/invasion of presynaptic axons. The findings presented here may be important for pharmaceutical development, where target engagement in the right compartment is essential.

  4. Dermatomes and the central organization of dermatomes and body surface regions in the spinal cord dorsal horn in rats.

    Science.gov (United States)

    Takahashi, Yuzuru; Chiba, Tanemichi; Kurokawa, Masahiro; Aoki, Yasuchika

    2003-07-14

    Dermatomes and the associated central projection fields were studied with the application of fluorescent neurotracer, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), to 21 reference points on rat trunk and hindlimb skin. Segmental distribution and rostrocaudal central level of dorsal root ganglion (DRG) neurons innervating reference points were examined and DiI-induced fluorescent areas were mapped in the horizontal plane through lamina II of the dorsal horn. Segmental levels of DRG neurons innervating reference points were generally identical to the level determined using dye-extravasation methods. However, innervation of the first digit was situated in the L4 dermatome, not the L3 reported previously using those methods. Generally, afferents from a reference point projected to a single field in the ipsilateral dorsal horn. Reference points on ventral and dorsal median lines of the trunk were represented bilaterally. Afferents from reference points located on the ventral median line of the hindlimb projected to two separate fields: one on the medial margin of spinal cord segments L2-L5 and the other on the medial half of spinal cord segment L5. From the distribution of central projection fields of reference points, central projection fields of dermatomes were revealed as even in shape and located within corresponding spinal cord segments. The arrangement of peripheral and central fields of dermatomes and body surface regions suggests that peripheral and central projection fields of cutaneous afferent fibers are reshaped from the common prototypical pattern that exhibits an orderly and evenly sequenced arrangement. Copyright 2003 Wiley-Liss, Inc.

  5. Structural and functional comparisons and production of recombinant crustacean hyperglycemic hormone (CHH) and CHH-like peptides from the mud crab Scylla olivacea.

    Science.gov (United States)

    Chang, Chih-Chun; Tsai, Kuo-Wei; Hsiao, Nai-Wan; Chang, Cheng-Yen; Lin, Chih-Lung; Watson, R Douglas; Lee, Chi-Ying

    2010-05-15

    Sco-CHH and Sco-CHH-L (CHH-like peptide), two structural variants of the crustacean hyperglycemic hormone family identified in the mud crab (Scylla olivacea), are presumably alternatively spliced gene products. In this study, Sco-CHH and Sco-CHH-L were isolated from the tissues using high performance liquid chromatography. Identity of the native peptides was confirmed using mass spectrometric (MS) analyses of purified materials and of trypsin-digested peptide fragments. Additionally, characterizations using circular dichroism (CD) spectrometry revealed that the 2 peptides have similar CD spectral profiles, showing they are composed mainly of alpha-helices, and are similarly thermo-stable with a melting temperature of 74-75 degrees C. Results of bioassays indicated that Sco-CHH exerted hyperglycemic and molt-inhibiting activity, whereas Sco-CHH-L did not. Further, recombinant Sco-CHH-Gly (rSco-CHH-Gly, a glycine extended Sco-CHH) and Sco-CHH-L (rSco-CHH-L) were produced using an Escherichia coli expression system, refolded, and purified. rSco-CHH-Gly was further alpha-amidated at the C-terminal end to produce rSco-CHH. MS analyses of enzyme-digested peptide fragments of rSco-CHH-Gly and rSco-CHH-L showed that the two peptides share a common disulfide bond pattern: C7-C43, C23-C39, and C26-C52. Circular dichroism analyses and hyperglycemic assay revealed that rSco-CHH and rSco-CHH-L resemble their native counterparts, in terms of CD spectral profiles, melting curve profiles, and biological activity. rSco-CHH-Gly has a lower alpha-helical content (32%) than rSco-CHH (47%), a structural deviation that may be responsible for the significant decrease in the biological activity of rSco-CHH-Gly. Finally, modeled structure of Sco-CHH and Sco-CHH-L indicated that they are similarly folded, each with an N-terminal tail region and 4 alpha-helices. Putative surface residues located in corresponding positions of Sco-CHH and Sco-CHH-L but with side chains of different properties

  6. Role of the Dorsal Hippocampus in Object Memory Load

    Science.gov (United States)

    Sannino, Sara; Russo, Fabio; Torromino, Giulia; Pendolino, Valentina; Calabresi, Paolo; De Leonibus, Elvira

    2012-01-01

    The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed…

  7. Compresión medular dorsal extradural por condroma

    Directory of Open Access Journals (Sweden)

    B. B. Srota

    1950-03-01

    Full Text Available For the first time in Argentine bibliography a chondroma of the vertebra with extradural dorsal medular compression, is described. The clinical characteristics of the onset by intermitent medular claudication of Dejerine and the painless evolution until surgical intervention, are stressed. The bibliography is put up to date and the radiographics signs and the pathologic anatomy of the chondromas, are studied.

  8. Syntabulin, a motor protein linker, controls dorsal determination.

    Science.gov (United States)

    Nojima, Hideaki; Rothhämel, Sophie; Shimizu, Takashi; Kim, Cheol-Hee; Yonemura, Shigenobu; Marlow, Florence L; Hibi, Masahiko

    2010-03-01

    In amphibian and teleost embryos, the dorsal determinants (DDs) are believed to be initially localized to the vegetal pole and then transported to the prospective dorsal side of the embryo along a microtubule array. The DDs are known to activate the canonical Wnt pathway and thereby promote the expression of genes that induce the dorsal organizer. Here, by identifying the locus of the maternal-effect ventralized mutant tokkaebi, we show that Syntabulin, a linker of the kinesin I motor protein, is essential for dorsal determination in zebrafish. We found that syntabulin mRNA is transported to the vegetal pole during oogenesis through the Bucky ball (Buc)-mediated Balbiani body-dependent pathway, which is necessary for establishment of animal-vegetal (AV) oocyte polarity. We demonstrate that Syntabulin is translocated from the vegetal pole in a microtubule-dependent manner. Our findings suggest that Syntabulin regulates the microtubule-dependent transport of the DDs, and provide evidence for the link between AV and dorsoventral axis formation.

  9. Evolutionary genetics of dorsal wing colour in Colias butterflies.

    NARCIS (Netherlands)

    Ellers, J.; Boggs, C.L.

    2004-01-01

    The evolution of butterfly wing colouration is strongly affected by its multiple functions and by the correlated evolution of wing colour elements. Both factors may prevent local adaptation to ecological conditions. We investigated one aspect of wing colouration, the degree of dorsal wing

  10. Dorsal striatal dopamine, food preference and health perception in humans

    NARCIS (Netherlands)

    Wallace, D.L.; Aarts, E.; Dang, L.C.; Greer, S.M.; Jagust, W.J.; D'Esposito, M.

    2014-01-01

    To date, few studies have explored the neurochemical mechanisms supporting individual differences in food preference in humans. Here we investigate how dorsal striatal dopamine, as measured by the positron emission tomography (PET) tracer [(18)F]fluorometatyrosine (FMT), correlates with food-related

  11. Treatment of acute and subacute dorsal perilunate fracture dislocations

    Directory of Open Access Journals (Sweden)

    Levent Kucuk

    2014-04-01

    Outcomes: Results of the perilunate fracture dislocations treated in acute or subacute phase by open reduction and internal fixation via dorsal approach are satisfactory. There is a strong demand for prospective, randomized studies to compare the results of different treatment modalities. [Hand Microsurg 2014; 3(1.000: 1-7

  12. A congenital mucocele of the anterior dorsal tongue

    NARCIS (Netherlands)

    Wong Chung, J.E.; Ensink, R.J.H.; Thijs, H.F.; Hoogen, F.J.A. van den

    2014-01-01

    We report on a new-born with a congenital mucocele on the anterior dorsal side of the tongue. The presentation as well as the differential diagnosis of congenital oral swellings is discussed. Because of breastfeeding problems the mucinous swelling was incised and drained two days after birth.

  13. A radiologic study on the urinary bladder following dorsal and ...

    African Journals Online (AJOL)

    Pneumocystography and positive contrast cystography using solutrast® were carried out immediately after surgery and on the second operative day following dorsal and ventral cystotomy in 22 adult mongrel dogs. In all the radiographs, there was no contrast observed in the abdominal cavity and the apex of the bladder had ...

  14. Development and functional significance of dorsal air bags in ...

    African Journals Online (AJOL)

    It appears that airbags may provide an effective intermediate insulatory mechanism for the nestlings while they are developing their thermoregulatory ability. Therefore, it is suggested that the dorsal air bags evolved primarily for thermoregulatory benefits to nestlings, although further research is required. Ostrich 2009, 80(1): ...

  15. Comparing root architectural models

    Science.gov (United States)

    Schnepf, Andrea; Javaux, Mathieu; Vanderborght, Jan

    2017-04-01

    Plant roots play an important role in several soil processes (Gregory 2006). Root architecture development determines the sites in soil where roots provide input of carbon and energy and take up water and solutes. However, root architecture is difficult to determine experimentally when grown in opaque soil. Thus, root architectural models have been widely used and been further developed into functional-structural models that are able to simulate the fate of water and solutes in the soil-root system (Dunbabin et al. 2013). Still, a systematic comparison of the different root architectural models is missing. In this work, we focus on discrete root architecture models where roots are described by connected line segments. These models differ (a) in their model concepts, such as the description of distance between branches based on a prescribed distance (inter-nodal distance) or based on a prescribed time interval. Furthermore, these models differ (b) in the implementation of the same concept, such as the time step size, the spatial discretization along the root axes or the way stochasticity of parameters such as root growth direction, growth rate, branch spacing, branching angles are treated. Based on the example of two such different root models, the root growth module of R-SWMS and RootBox, we show the impact of these differences on simulated root architecture and aggregated information computed from this detailed simulation results, taking into account the stochastic nature of those models. References Dunbabin, V.M., Postma, J.A., Schnepf, A., Pagès, L., Javaux, M., Wu, L., Leitner, D., Chen, Y.L., Rengel, Z., Diggle, A.J. Modelling root-soil interactions using three-dimensional models of root growth, architecture and function (2013) Plant and Soil, 372 (1-2), pp. 93 - 124. Gregory (2006) Roots, rhizosphere and soil: the route to a better understanding of soil science? European Journal of Soil Science 57: 2-12.

  16. Dorsal Phalloplasty to Preserve Penis Length after Penile Prosthesis Implantation.

    Science.gov (United States)

    Shaeer, Osama; Shaeer, Kamal; Rahman, Islam A

    2017-02-01

    Following penile prosthesis implantation (PPI), patients may complain of a decrease in visible penis length. A dorsal phalloplasty defines the penopubic junction by tacking pubic skin to the pubis, revealing the base of the penis. This study aimed to evaluate the efficacy of a dorsal phalloplasty in increasing the visible penis length following PPI. An inflatable penile prosthesis was implanted in 13 patients with severe erectile dysfunction (ED) at the Kamal Shaeer Hospital, Cairo, Egypt, from January 2013 to May 2014. During the surgery, nonabsorbable tacking sutures were used to pin the pubic skin to the pubis through the same penoscrotal incision. Intraoperative penis length was measured before and after the dorsal phalloplasty. Overall patient satisfaction was measured on a 5-point rating scale and patients were requested to subjectively compare their postoperative penis length with memories of their penis length before the onset of ED. Intraoperatively, the dorsal phalloplasty increased the visible length of the erect penis by an average of 25.6%. The average length before and after tacking was 10.2 ± 2.9 cm and 13.7 ± 2.8 cm, respectively (P <0.002). Postoperatively, seven patients (53.8%) reported a longer penis, five patients (38.5%) reported no change in length and one patient (7.7%) reported a slightly shorter penis. The mean overall patient satisfaction score was 4.9 ± 0.3. None of the patients developed postoperative complications. A dorsal phalloplasty during PPI is an effective method of increasing visible penis length, therefore minimising the impression of a shorter penis after implantation.

  17. Plantar and dorsal foot loading measurements in patients after rotationplasty.

    Science.gov (United States)

    Hillmann, A; Rosenbaum, D; Winkelmann, W

    2000-06-01

    The present study investigated the plantar and dorsal foot loading patterns inside the prosthesis of patients after rotationplasty. In vivo foot pressure distribution measurements during free walking in rotationplasty patients at an average follow-up of 10.4 years after surgery. Fourteen subjects participated in the study and were measured during free walking. Capacitive pressure sensitive insoles were worn inside the shaft of the prosthesis either on the plantar or the dorsal aspect of the foot. Between 5 and 15 steps (mean 10.5) during full gait were selected and averaged to present a typical loading pattern for the individual patient. The measurements were reproducible and indicated that the main loading areas of the rotated foot inside the prosthesis are medially on the dorsal aspect and in the heel and toe region or the heel and midfoot region on the plantar aspect. The dorsal loading area was smaller than the plantar area (P=0.003). The force was higher on the plantar than on the dorsal aspect (P=0.005) but the loading time was shorter (P=0.008). In patients with callosities the high pressure areas coincided with the affected regions. The information gained from the pressure measurements support the understanding of foot loading characteristics in this anatomically and biomechanically unusual situation. This knowledge may be used to support the fitting process of new prosthetic designs for patients after rotationplasty. Foot loading capacity is one of the main factors limiting the activity level of rotationplasty patients. Therefore, a better understanding of foot loading characteristics might help to prevent overloading of certain foot structures and eventually improve the prosthetic fit with a direct benefit to the individual patient.

  18. Involvement of the crustacean hyperglycemic hormone (CHH) in the physiological compensation of the freshwater crayfish Cherax quadricarinatus to low temperature and high salinity stress.

    Science.gov (United States)

    Prymaczok, Natalia C; Pasqualino, Valeria M; Viau, Verónica E; Rodríguez, Enrique M; Medesani, Daniel A

    2016-02-01

    This study was aimed at determining the role of the crustacean hyperglycemic hormone (CHH) in the physiological compensation to both saline and thermal stress, in the freshwater crayfish Cherax quadricarinatus. By determining the expression of the CHH gene in the eyestalk of juvenile crayfish, we found that maximal induction of CHH was induced at high salinity (10 g/L) and low temperature (20 °C). In order to investigate the role of CHH in the physiological compensation to such stressful conditions, recombinant CHH was supplied to stressed animals. CHH-injected crayfish showed increased hemolymphatic levels of glucose, in accordance with a significant utilization of glycogen reserves from the hepatopancreas. Furthermore, CHH administration allowed stressed animals to regulate hemolymphatic sodium and potassium at more constant levels than controls. Taken together, these results suggest a relevant role of CHH in increasing the energy available intended for processes involved in the physiological compensation of C. quadricarinatus to both saline and thermal stress.

  19. Eicosapentaenoic acid-enriched phosphatidylcholine isolated from Cucumaria frondosa exhibits anti-hyperglycemic effects via activating phosphoinositide 3-kinase/protein kinase B signal pathway.

    Science.gov (United States)

    Hu, Shiwei; Xu, Leilei; Shi, Di; Wang, Jingfeng; Wang, Yuming; Lou, Qiaoming; Xue, Changhu

    2014-04-01

    Eicosapentaenoic acid-enriched phosphatidylcholine was isolated from the sea cucumber Cucumaria frondosa (Cucumaria-PC) and its effects on streptozotocin (STZ)-induced hyperglycemic rats were investigated. Male Sprague-Dawley rats were randomly divided into normal control, model control (STZ), low- and high-dose Cucumaria-PC groups (STZ + Cucumaria-PC at 25 and 75 mg/Kg·b·wt, intragastrically, respectively). Blood glucose, insulin, glycogen in liver and gastrocnemius were determined over 60 days. Insulin signaling in the rats' gastrocnemius was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The results showed that Cucumaria-PC significantly decreased blood glucose level, increased insulin secretion and glycogen synthesis in diabetic rats. RT-PCR analysis revealed that Cucumaria-PC significantly promoted the expressions of glycometabolism-related genes of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB), and glucose transporter 4 (GLUT4) in gastrocnemius. Western blotting assay demonstrated that Cucumaria-PC remarkably enhanced the proteins abundance of IR-β, PI3K, PKB, GLUT4, as well as phosphorylation of Tyr-IR-β, p85-PI3K, Ser473-PKB (P < 0.05 and P < 0.01). These findings suggested that Cucumaria-PC exhibited significant anti-hyperglycemic activities through up-regulating PI3K/PKB signal pathway mediated by insulin. Nutritional supplementation with Cucumaria-PC, if validated for human studies, may offer an adjunctive therapy for diabetes mellitus. Copyright © 2013 The Society for Biotechnology, Japan. All rights reserved.

  20. Reduced CGP12177 binding to cardiac {beta}-adrenoceptors in hyperglycemic high-fat-diet-fed, streptozotocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Thackeray, James T.; Parsa-Nezhad, Maryam; Kenk, Miran; Thorn, Stephanie L. [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, Ottawa, Ontario, K1H8M5 (Canada); Kolajova, Maria [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Beanlands, Rob S.B. [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, Ottawa, Ontario, K1H8M5 (Canada); DaSilva, Jean N., E-mail: jdasilva@ottawaheart.ca [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, Ottawa, Ontario, K1H8M5 (Canada)

    2011-10-15

    Introduction: Abnormal sympathetic nervous system and {beta}-adrenoceptor ({beta}-AR) signaling is associated with diabetes. [{sup 3}H]CGP12177 is a nonselective {beta}-AR antagonist that can be labeled with carbon-11 for positron emission tomography. The aim of this study was to examine the suitability of this tracer for evaluation of altered {beta}-AR expression in diabetic rat hearts. Methods: Ex vivo biodistribution with [{sup 3}H]CGP12177 was carried out in normal Sprague-Dawley rats for evaluation of specific binding and response to continuous {beta}-AR stimulation by isoproterenol. In a separate group, high-fat-diet feeding imparted insulin resistance and a single intraperitoneal injection of streptozotocin (STZ) or vehicle evoked hyperglycemia (blood glucose >11 mM). [{sup 3}H]CGP12177 biodistribution was assessed at 2 and 8 weeks post-STZ to measure {beta}-AR binding in heart, 30 min following tracer injection. Western blotting of {beta}-AR subtypes was completed in parallel. Results: Infusion of isoproterenol over 14 days did not affect cardiac binding of [{sup 3}H]CGP12177. Approximately half of rats treated with STZ exhibited sustained hyperglycemia and progressive hypoinsulinemia. Myocardial [{sup 3}H]CGP12177 specific binding was unchanged at 2 weeks post-STZ but significantly reduced by 30%-40% at 8 weeks in hyperglycemic but not euglycemic STZ-treated rats compared with vehicle-treated controls. Western blots supported a significant decrease in {beta}{sub 1}-AR in hyperglycemic rats. Conclusions: Reduced cardiac [{sup 3}H]CGP12177 specific binding in the presence of sustained hyperglycemia corresponds to a decrease in relative {beta}{sub 1}-AR expression. These data indirectly support the use of [{sup 11}C]CGP12177 for assessment of cardiac dysfunction in diabetes.

  1. Accuracy and Time Delay of Glucose Measurements of Continuous Glucose Monitoring and Bedside Artificial Pancreas During Hyperglycemic and Euglycemic Hyperinsulinemic Glucose Clamp Study.

    Science.gov (United States)

    Kuroda, Akio; Taniguchi, Satoshi; Akehi, Yuko; Mori, Hiroyasu; Tamaki, Motoyuki; Suzuki, Reiko; Otsuka, Yinhua; Matsuhisa, Munehide

    2017-11-01

    Glucose values of continuous glucose monitoring (CGM) have time delays compared with plasma glucose (PG) values. The artificial pancreas (STG-55, Nikkiso, Japan) (AP), which measures venous blood glucose directly, also has a time delay because of the long tubing lines from sampling vessel to the glucose sensor. We investigate accuracy and time delay of CGM and AP in comparison with PG values during 2-step glucose clamp study. Seven patients with type 2 diabetes and 2 healthy volunteers were included in this study. CGM (Enlite sensor, Medtronic, Northridge, CA, USA) was attached on the day before the experiment. Hyperglycemic (200 mg/dL) clamp was performed for 90 minutes, followed by euglycemic (100 mg/dL) hyperinsulinemic (100 μU/mL) clamp for 90-120 minutes using AP. CGM sensor glucose was calibrated just before and after the clamp study. AP and CGM values were compared with PG values. AP values were significantly lower than PG values at 5, 30 minute during hyperglycemic clamp. In comparison, CGM value at 0 minute was significantly higher, and its following values were almost significantly lower than PG values. The time delay of AP and CGM values to reach maximum glucose levels were 5.0 ± 22.3 (NS) and 28.6 ± 32.5 ( P < .05) min, respectively. Mean absolute rate difference of CGM was significantly higher than AP (24.0 ± 7.6 vs 15.3 ± 4.6, P < .05) during glucose rising period (0-45 min); however, there were no significant differences during other periods. Both CGM and AP failed to follow plasma glucose values during nonphysiologically rapid glucose rising, but indicated accurate values during physiological glucose change.

  2. Anti-hyperglycemic effect, inhibition of inflammatory cytokines expression, and histopathology profile in streptozotocin-induced diabetic rats treated with Arracacia tolucensis aerial-parts extracts.

    Science.gov (United States)

    García-Galicia, Mary Carmen; Burgueño-Tapia, Eleuterio; Romero-Rojas, Andrés; García-Zebadúa, Julio César; Cornejo-Garrido, Jorge; Ordaz-Pichardo, Cynthia

    2014-02-27

    Arracacia tolucensis is a medicinal plant used in northeast of Mexico as a remedy to treat people with Diabetes mellitus (DM); however, there are no scientific studies that support this information. Thus, we evaluated the anti-hyperglycemic effect of the hexane, ethyl acetate and ethanol extracts from aerial parts in streptozotocin-induced diabetic rats. DM was induced in Wistar male rats by single intraperitoneal injection of streptozotocin (STZ 50mg/kg). After STZ-induction, hyperglycemic rats were treated with all three extracts orally at a single dose (250 mg/kg) each 48 h for 21 days. Glibenclamide (1mg/kg) was used as a reference drug. The fasting blood glucose levels, the hematic biometry and biochemical profiles, and the inhibition of inflammatory cytokines expression were estimated. Histopathology analysis of pancreas, liver, spleen, and kidney tissue was carried out. Ours results showed that ethyl acetate extract decreased blood glucose levels significantly (75%, p< 0.05) when compared to diabetic rats and controlled the body weight loss; the lipids level did not change, but the enzyme levels of aspartate aminotransferase and alanine aminotransferase decreased significantly (60.83% and 66.16%, respectively, p< 0.05) and inhibited the expression of inflammatory cytokines,with respect to diabetic rats. Histopathology injury was not observed; by contrast repair of islet of Langerhans was exhibited. These results validate the use of Arracacia tolucensis as a treatment against DM and suggests it is suitable to continue studies for its safe therapeutic use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Anti-atherogenic effect of trivalent chromium-loaded CPMV nanoparticles in human aortic smooth muscle cells under hyperglycemic conditions in vitro

    Science.gov (United States)

    Ganguly, Rituparna; Wen, Amy M.; Myer, Ashley B.; Czech, Tori; Sahu, Soumyadip; Steinmetz, Nicole F.; Raman, Priya

    2016-03-01

    Atherosclerosis, a major macrovascular complication associated with diabetes, poses a tremendous burden on national health care expenditure. Despite extensive efforts, cost-effective remedies are unknown. Therapies for atherosclerosis are challenged by a lack of targeted drug delivery approaches. Toward this goal, we turn to a biology-derived drug delivery system utilizing nanoparticles formed by the plant virus, Cowpea mosaic virus (CPMV). The aim herein is to investigate the anti-atherogenic potential of the beneficial mineral nutrient, trivalent chromium, loaded CPMV nanoparticles in human aortic smooth muscle cells (HASMC) under hyperglycemic conditions. A non-covalent loading protocol is established yielding CrCl3-loaded CPMV (CPMV-Cr) carrying 2000 drug molecules per particle. Using immunofluorescence microscopy, we show that CPMV-Cr is readily taken up by HASMC in vitro. In glucose (25 mM)-stimulated cells, 100 nM CPMV-Cr inhibits HASMC proliferation concomitant to attenuated proliferating cell nuclear antigen (PCNA, proliferation marker) expression. This is accompanied by attenuation in high glucose-induced phospho-p38 and pAkt expression. Moreover, CPMV-Cr inhibits the expression of pro-inflammatory cytokines, transforming growth factor-β (TGF-β) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), in glucose-stimulated HASMCs. Finally glucose-stimulated lipid uptake is remarkably abrogated by CPMV-Cr, revealed by Oil Red O staining. Together, these data provide key cellular evidence for an atheroprotective effect of CPMV-Cr in vascular smooth muscle cells (VSMC) under hyperglycemic conditions that may promote novel therapeutic ventures for diabetic atherosclerosis.

  4. Meniscus root repair.

    Science.gov (United States)

    Vyas, Dharmesh; Harner, Christopher D

    2012-06-01

    Root tears are a subset of meniscal injuries that result in significant knee joint pathology. Occurring on either the medial or lateral side, root tears are defined as radial tears or avulsions of the posterior horn attachment to bone. After a root tear, there is a significant increase in tibio-femoral contact pressure concomitant with altered knee joint kinematics. Previous cadaver studies from our institution have shown that root repair of the medial meniscus is successful in restoring joint biomechanics to within normal limits. Indications for operative management of meniscal root tears include (1) a symptomatic medial meniscus root tear with minimal arthritis and having failed non-operative treatment, and (2) a lateral root tear in associated with an ACL tear. In this review, we describe diagnosis, imaging, patient selection, and arthroscopic surgical technique of medial and lateral meniscus root injuries. In addition we highlight the pearls of repair technique, associated complications, post-operative rehabilitation regimen, and expected outcomes.

  5. Volar versus dorsal fixed-angle fixation of dorsally unstable extra-articular distal radius fractures: a biomechanic study.

    Science.gov (United States)

    McCall, Todd A; Conrad, Bryan; Badman, Brian; Wright, Thomas

    2007-01-01

    To evaluate and compare the biomechanic rigidity and strength of 3 fixed-angle plates used to treat extra-articular distal radius fractures that are dorsally unstable. Volar fixed-angle plates were compared with a dorsal fixed-angle nail plate. Three plate constructs were tested: the dorsal nail plate (DNP), distal volar radius (DVR) plate, and locking compression plate (LCP) volar distal radius plate. With anatomic, third-generation, artificial composite radii, dorsally unstable extra-articular distal radius fracture models were made by cutting a wedge osteotomy with an 8-mm dorsal gap 1 cm from the articular surface. These models were then fixed with the 3 implants by the method recommended by the manufacturer. The proximal radii of each specimen were attached to the base of a materials testing machine with a probe centered at the radial side of the lunate fossa. The specimens were loaded at a constant rate to failure under axial compression. Load and displacement were plotted graphically, and the resulting rigidities and strengths of each plate were assessed statistically. The DVR group had significantly greater stiffness than the LCP group. The DVR group had significantly higher maximum loads than both the DNP and LCP groups. There were no significant differences in yield loads. Both the DNP and DVR groups had significantly less displacement at yield than the LCP group. These 3 groups had similar yield loads. However, the LCP was less stiff than the DVR and had more displacement at yield than both the DVR and DNP. The yield load of all 3 implants was much higher than previously described loads for active wrist and finger motion.

  6. Tooth Eruption without Roots

    OpenAIRE

    Wang, X.-P.

    2013-01-01

    Root development and tooth eruption are very important topics in dentistry. However, they remain among the less-studied and -understood subjects. Root development accompanies rapid tooth eruption, but roots are required for the movement of teeth into the oral cavity. It has been shown that the dental follicle and bone remodeling are essential for tooth eruption. So far, only limited genes have been associated with root formation and tooth eruption. This may be due to the diffic...

  7. Rooting an Android Device

    Science.gov (United States)

    2015-09-01

    o 8-GB Memory o Intel Xeon X5472 Central Processing Unit (CPU)  64-bit quad and dual-core  3.0 GHz 3. Rooting Android Devices The rooting...root access has been granted. 4. Conclusion This document serves as a tutorial on how to grant user administrative privilege to an Android device by

  8. File list: Unc.Lar.20.AllAg.Dorsal_mesothoracic_disc [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Lar.20.AllAg.Dorsal_mesothoracic_disc dm3 Unclassified Larvae Dorsal mesothorac...ic disc http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Unc.Lar.20.AllAg.Dorsal_mesothoracic_disc.bed ...

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  11. File list: Oth.Lar.50.AllAg.Dorsal_mesothoracic_disc [Chip-atlas[Archive

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    Full Text Available Oth.Lar.50.AllAg.Dorsal_mesothoracic_disc dm3 TFs and others Larvae Dorsal mesothor...acic disc SRX151958,SRX151957,SRX151959,SRX151956 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Lar.50.AllAg.Dorsal_mesothoracic_disc.bed ...

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  14. File list: Oth.Lar.20.AllAg.Dorsal_mesothoracic_disc [Chip-atlas[Archive

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    Full Text Available Oth.Lar.20.AllAg.Dorsal_mesothoracic_disc dm3 TFs and others Larvae Dorsal mesothor...acic disc SRX151957,SRX151959,SRX151958,SRX151956 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Lar.20.AllAg.Dorsal_mesothoracic_disc.bed ...

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  1. File list: Oth.Lar.10.AllAg.Dorsal_mesothoracic_disc [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Lar.10.AllAg.Dorsal_mesothoracic_disc dm3 TFs and others Larvae Dorsal mesothor...acic disc SRX151957,SRX151958,SRX151959,SRX151956 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Lar.10.AllAg.Dorsal_mesothoracic_disc.bed ...

  2. File list: Unc.Lar.10.AllAg.Dorsal_mesothoracic_disc [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. Curcumol Promotes Vascular Endothelial Growth Factor (VEGF)-Mediated Diabetic Wound Healing in Streptozotocin-Induced Hyperglycemic Rats.

    Science.gov (United States)

    Zhou, Jie; Ni, Maowei; Liu, Xia; Ren, Zeming; Zheng, Zhiguo

    2017-01-31

    BACKGROUND Wound healing in chronic diabetic mellitus is mainly associated with the management of angiogenesis. The angiogenic mechanism of vascular endothelial growth factor (VEGF) has been widely studied in the context of diabetic ulcers. The aim of this study was to investigate the wound-healing potential of curcumol in streptozotocin-induced diabetic rats. MATERIAL AND METHODS Sixty male SD (Sprague Dawley) rats were purchased and randomly assigned into four groups: a control group and a model group treated with blank ointment, a high-dose curcumol group, and a low-dose curcumol group. The number of animals in each group was 15. Diabetes was induced by an intraperitoneal injection of streptozotocin. Two cutaneous wounds were incised at the dorsal region of all the experimental animals. Wound healing was assessed for all animal groups by observing the rate of wound closure. The expression of VEGF at the wound sites was studied by immunohistochemical staining to evaluate the vascular endothelial cell reaction. VEGF protein and related mRNA levels were analyzed by Western blotting and RT-PCR (reverse transcription-polymerase chain reaction). RESULTS Curcumol treatment significantly increased the rates of wound closure in treated animals, and hence wound healing was drastically enhanced for treatment groups compared to control groups. Histological observations and related mRNA and protein levels showed a higher VEGF expression in the treatment groups. CONCLUSIONS Our analyses clearly suggested that the observed enhancement in wound healing as a result of curcumol administration was attributable to VEGF-mediated angiogenesis.

  4. Dorsal finger texture recognition: Investigating fixed-length SURF

    DEFF Research Database (Denmark)

    Hartung, Daniel; Kückelhahn, Jesper

    2012-01-01

    We seek to create fixed-length features from dorsal finger skin images extracted by the SURF interest point detector to combine it in the privacy enhancing helper data scheme. The source of the biometric samples is the GUC45 database which features finger vein, fingerprint and dorsal finger skin...... images for modality fusion. First, the region of interest (ROI) is extracted, after which SURF features are extracted, and finally two different approaches for creating fixed length feature vectors are applied. SURF performance on the ROI is comparable to the PolyU database reported in the literature...... the complexity of the SURF matching scheme, a reduction in run-time of 75%–80% has been achieved, with only minimal precision loss; EER increases from 0.74% to 1%. The complexity of the matching can be reduced from O(n2) to constant time, but at a higher precision cost and resulting in an EER of 16.51%....

  5. The dorsal approach to the distal radioulnar joint.

    Science.gov (United States)

    van Schoonhoven, Joerg; Herbert, Timothy

    2004-03-01

    A number of different disorders or injuries require surgical intervention at the distal radioulnar joint. Depending on the underlying condition, the distal radioulnar joint is traditionally exposed via a dorsal or, less commonly, a palmar approach. Occasionally, as in the case of fractures of the distal ulna or ulnar styloid process, a lateral approach may be chosen. We describe an operative technique for a dorsal approach to the distal radioulnar joint that we have found to be extremely useful for a wide range of different pathologies. This technique not only allows excellent visualization of the head of the ulna and the distal radioulnar joint, but also the triangular fibrocartilage complex and the ulnocarpal joint as well. Furthermore, it provides a simple means of restoring normal alignment and stability to the distal radioulnar joint and the ulnar side of the carpus.

  6. Neural dynamics of phonological processing in the dorsal auditory stream.

    Science.gov (United States)

    Liebenthal, Einat; Sabri, Merav; Beardsley, Scott A; Mangalathu-Arumana, Jain; Desai, Anjali

    2013-09-25

    Neuroanatomical models hypothesize a role for the dorsal auditory pathway in phonological processing as a feedforward efferent system (Davis and Johnsrude, 2007; Rauschecker and Scott, 2009; Hickok et al., 2011). But the functional organization of the pathway, in terms of time course of interactions between auditory, somatosensory, and motor regions, and the hemispheric lateralization pattern is largely unknown. Here, ambiguous duplex syllables, with elements presented dichotically at varying interaural asynchronies, were used to parametrically modulate phonological processing and associated neural activity in the human dorsal auditory stream. Subjects performed syllable and chirp identification tasks, while event-related potentials and functional magnetic resonance images were concurrently collected. Joint independent component analysis was applied to fuse the neuroimaging data and study the neural dynamics of brain regions involved in phonological processing with high spatiotemporal resolution. Results revealed a highly interactive neural network associated with phonological processing, composed of functional fields in posterior temporal gyrus (pSTG), inferior parietal lobule (IPL), and ventral central sulcus (vCS) that were engaged early and almost simultaneously (at 80-100 ms), consistent with a direct influence of articulatory somatomotor areas on phonemic perception. Left hemispheric lateralization was observed 250 ms earlier in IPL and vCS than pSTG, suggesting that functional specialization of somatomotor (and not auditory) areas determined lateralization in the dorsal auditory pathway. The temporal dynamics of the dorsal auditory pathway described here offer a new understanding of its functional organization and demonstrate that temporal information is essential to resolve neural circuits underlying complex behaviors.

  7. Mitotic activity in dorsal epidermis of Rana pipiens.

    Science.gov (United States)

    Garcia-Arce, H.; Mizell, S.

    1972-01-01

    Study of statistically significant rhythms of mitotic division in dorsal epidermis of frogs, Rana pipiens, exposed to a 12:12 light:dark environment for 14 days. The results include the findings that (1) male animals have a primary period of 22 hr in summer and 18 hr in winter, (2) female animals have an 18 hr period, and (3) parapinealectomy and blinding abolish the rhythm.

  8. Complete agenesis of the dorsal pancreas: Case report with ...

    African Journals Online (AJOL)

    Agenesis of the dorsal pancreas 73 http://dx.doi.org/10.4314/mmj.v27i2.9. Introduction. A 35-year-old male presented with a three-day history of epigastric pain and vomiting. Six months prior to presentation, the patient was diagnosed with type 2 diabetes mellitus and was on an insulin therapy regimen. He had no relevant.

  9. Cervical and middle dorsal actinomycetomas from Guerrero State, Mexico.

    Science.gov (United States)

    Estrada-Chávez, Guadalupe E; Estrada, Roberto; Fernandez, Ramon; Arenas, Roberto; Reyes, Alain; Guevara, Cindy; Chávez-López, Guadalupe

    2017-11-01

    Mycetomas are frequent subcutaneous mycoses with typical clinical characteristics such as sinuses, blood-stained, serous, or purulent exudates as well as local swelling. Even though the most commonly affected areas are the lower limbs, we report four cases affecting the neck and midback regions, of which three were young females. We draw attention to the importance of early identification of these cases for prevention and specific treatment in order to avoid severe consequences or irreversible complications such as quadriplegia. To document the occurrence of cervical spine and middle dorsal thoracic mycetomas, as well as their severity, clinical manifestations, and secondary complications. This was an observational and descriptive study in which we reviewed cases with neck and middle dorsal thoracic mycetomas diagnosed at the Acapulco General Hospital of Guerrero State, Mexico. We describe the cases including the mechanism of inoculation, neurological symptoms, and severity. We describe three cases initially diagnosed clinically as cervical mycetomas and one in the middle dorsal thoracic region. All the cases were diagnosed at the Acapulco General Hospital of Guerrero State in Mexico. © 2017 The International Society of Dermatology.

  10. Alzheimer disease: functional abnormalities in the dorsal visual pathway.

    LENUS (Irish Health Repository)

    Bokde, Arun L W

    2012-02-01

    PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered activation compared with age-matched healthy control (HC) subjects during a task that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The study was performed in accordance with the Declaration of Helsinki, with institutional ethics committee approval, and all subjects provided written informed consent. Two tasks were performed to investigate neural function: face matching and location matching. Twelve patients with mild AD and 14 age-matched HC subjects were included. Brain activation was measured by using functional magnetic resonance imaging. Group statistical analyses were based on a mixed-effects model corrected for multiple comparisons. RESULTS: Task performance was not statistically different between the two groups, and within groups there were no differences in task performance. In the HC group, the visual perception tasks selectively activated the visual pathways. Conversely in the AD group, there was no selective activation during performance of these same tasks. Along the dorsal visual pathway, the AD group recruited additional regions, primarily in the parietal and frontal lobes, for the location-matching task. There were no differences in activation between groups during the face-matching task. CONCLUSION: The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.

  11. A cellular Potts model of germband retraction and dorsal closure

    Science.gov (United States)

    Hutson, M. Shane; Rohner, Jason; Crews, Sarah; McCleery, W. Tyler; Robinson, W. Bradley

    2011-03-01

    Germband retraction and dorsal closure are critical morphogenetic events in fruit fly embryogenesis. Both involve the coordinated reshaping of two epitheloid tissues -- germband (GB) and amnioserosa (AS). The GB is initially curled into a U-shape with the AS between the arms of the U. Retraction leaves the embryo's dorsal surface covered by AS cells which then contract to pull lateral parts of the GB up to cover the dorsal surface. We have simulated these events using a cellular Potts model. The model is 3D with several generalized cell types: a central yolk; a surrounding monolayer of AS and GB cells with epithelial polarization; and an outer vitelline membrane enclosing the cells and a perivitelline fluid. The model also incorporates several critical cell behaviors: polarized apical constriction of AS cells; controlled relaxation of stretched GB cells; and differentiation of GB cells at the GB-AS interface so that these cells then contract a supracellular purse-string and extend filopodia that reach across the AS and zip together the GB's approaching lateral flanks. We will discuss how all of these components are necessary to reproduce normal tissue motions and those observed during laser microsurgery experiments. Supported by NSF Grant IOB-0545679.

  12. Bulbar urethroplasty using the dorsal approach: current techniques

    Directory of Open Access Journals (Sweden)

    Barbagli Guido

    2003-01-01

    Full Text Available INTRODUCTION: The use of flaps or grafts is mandatory in patients with longer and complex strictures. In 1995-96 we described a new dorsal onlay graft urethroplasty. Over time, our original technique was better defined and changed. Now this procedure (also named Barbagli technique has been greeted with a fair amount of enthusiasm in Europe and in the United States. SURGICAL TECHNIQUE: The patient is placed in normal lithotomy position, and a midline perineo-scrotal incision is made. The bulbar urethra is then free from the bulbo-cavernous muscles, and is dissected from the corpora cavernosa. The urethra is completely mobilized from the corpora cavernosa, it is rotated 180 degrees, and is incised along its dorsal surface. The graft (preputial skin or buccal mucosa or the flap is fixed and quilted to the tunica albuginea of the corporal bodies. The right mucosal margin of the opened urethra is sutured to the right side of the patch-graft. The urethra is rotated back into its original position. The left urethral margin is sutured to the left side of the patch graft and to the corporal bodies, and the grafted area is entirely covered by the urethral plate. The bulbo-cavernous muscles are approximated over the grafted area. A 16F silicone Foley catheter is left in place. COMMENTS: Dorsal onlay graft urethroplasty is a versatile procedure that may be combined with various substitute materials like preputial skin, buccal mucosa grafts or pedicled flaps.

  13. Dorsal prevertebral lesions in Wegener granulomatosis: report on four cases.

    Science.gov (United States)

    Barreto, Paulo; Pagnoux, Christian; Luca, Luminata; Aouizerate, Jessie; Ortigueira, Isabel; Cohen, Pascal; Muller, Géraldine; Guillevin, Loïc

    2011-01-01

    Retroperitoneal fibrosis has been reported in several patients with Wegener granulomatosis (WG), but only three isolated cases of dorsal prevertebral lesions, closely resembling fibrosing mediastinitis, have been published so far. We describe four new WG patients (two men, two women), 49-59 years old at diagnosis, with dorsal prevertebral lesions, mainly right-sided, and with adjacent pleural thickening in two. These lesions were detected on computed-tomography scans at diagnosis in two patients, and occurred later in the two others. Only one of them had mild back pain. Two patients' lesions were biopsied, revealing granulomatous inflammation. In one patient, the lesion regressed under WG treatment. Lesion size did not change in the remainings. Intralesional calcifications appeared in two. None of the patients had local bone erosion, vascular or neurological complications. These prevertebral lesions might represent a dorsal form of retroperitoneal fibrosis in WG, but usually with a more benign presentation and course. WG should be included in the differential diagnosis of fibrosing mediastinitis (with tuberculosis, neoplastic diseases, sarcoidosis, histiocytosis and inflammatory pseudotumor), which may have a similar radiological appearance. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  14. Compound dorsal dislocation of lunate with trapezoid fracture

    Directory of Open Access Journals (Sweden)

    Bong-Sung Kim

    2016-12-01

    Full Text Available We report about a dorsal dislocation of the lunate accompanied by a trapezoid fracture in a 41-year old male patient after a motorcycle accident. The lunate dislocation with no dorsal or volar intercalated segment instability (DISI, VISI was diagnosed by x-ray whereas the trapezoid fracture was only diagnosable by computed tomography. A closed reduction and internal fixation of the lunate by two Kirschner wires was performed, the trapezoid fracture was conservatively treated. Surgery was followed by immobilization, intense physiotherapy and close follow-up. Even though complaints such as swelling and pain subsided during the course of rehabilitation, partial loss of strength and range of motion remained even after 16 months. In conclusion, a conservative treatment of trapezoid fractures seems to be sufficient in most cases. Closed reduction with Kwire fixation led to an overall satisfactory result in our case. For dorsal lunate dislocations in general, open reduction should be performed when close reduction is unsuccessful or DISI/VISI are observed in radiographs after attempted close reduction.

  15. A afferent fibers are involved in the pathology of central changes in the spinal dorsal horn associated with myofascial trigger spots in rats.

    Science.gov (United States)

    Meng, Fei; Ge, Hong-You; Wang, Yong-Hui; Yue, Shou-Wei

    2015-11-01

    A afferent fibers have been reported to participate in the development of the central sensitization induced by inflammation and injuries. Current evidence suggests that myofascial trigger points (MTrPs) induce central sensitization in the related spinal dorsal horn, and clinical studies indicate that A fibers are associated with pain behavior. Because most of these clinical studies applied behavioral indexes, objective evidence is needed. Additionally, MTrP-related neurons in dorsal root ganglia and the spinal ventral horn have been reported to be smaller than normal, and these neurons were considered to be related to A fibers. To confirm the role of A fibers in MTrP-related central changes in the spinal dorsal horn, we studied central sensitization as well as the size of neurons associated with myofascial trigger spots (MTrSs, equivalent to MTrPs in humans) in the biceps femoris muscle of rats and provided some objective morphological evidence. Cholera toxin B subunit-conjugated horseradish peroxidase was applied to label the MTrS-related neurons, and tetrodotoxin was used to block A fibers specifically. The results showed that in the spinal dorsal horn associated with MTrS, the expression of glutamate receptor (mGluR1α/mGluR5/NMDAR1) increased, while the mean size of MTrS-related neurons was smaller than normal. After blocking A fibers, these changes reversed to some extent. Therefore, we concluded that A fibers participated in the development and maintenance of the central sensitization induced by MTrPs and were related to the mean size of neurons associated with MTrPs in the spinal dorsal horn.

  16. Tooth Eruption without Roots

    Science.gov (United States)

    2013-01-01

    Root development and tooth eruption are very important topics in dentistry. However, they remain among the less-studied and -understood subjects. Root development accompanies rapid tooth eruption, but roots are required for the movement of teeth into the oral cavity. It has been shown that the dental follicle and bone remodeling are essential for tooth eruption. So far, only limited genes have been associated with root formation and tooth eruption. This may be due to the difficulties in studying late stages of tooth development and tooth movement and the lack of good model systems. Transgenic mice with eruption problems and short or no roots can be used as a powerful model for further deciphering of the cellular, molecular, and genetic mechanisms underlying root formation and tooth eruption. Better understanding of these processes can provide hints on delivering more efficient dental therapies in the future. PMID:23345536

  17. Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study.

    Science.gov (United States)

    Mesejo, Alfonso; Montejo-González, Juan Carlos; Vaquerizo-Alonso, Clara; Lobo-Tamer, Gabriela; Zabarte-Martinez, Mercedes; Herrero-Meseguer, Jose Ignacio; Acosta-Escribano, Jose; Blesa-Malpica, Antonio; Martinez-Lozano, Fátima

    2015-11-09

    Although standard enteral nutrition is universally accepted, the use of disease-specific formulas for hyperglycemic patients is still controversial. This study examines whether a high-protein diabetes-specific formula reduces insulin needs, improves glycemic control and reduces ICU-acquired infection in critically ill, hyperglycemic patients on mechanical ventilation (MV). This was a prospective, open-label, randomized (web-based, blinded) study conducted at nine Spanish ICUs. The patient groups established according to the high-protein formula received were: group A, new-generation diabetes-specific formula; group B, standard control formula; group C, control diabetes-specific formula. Inclusion criteria were: expected enteral nutrition ≥5 days, MV, baseline glucose >126 mg/dL on admission or >200 mg/dL in the first 48 h. Exclusion criteria were: APACHE II ≤10, insulin-dependent diabetes, renal or hepatic failure, treatment with corticosteroids, immunosuppressants or lipid-lowering drugs and body mass index ≥40 kg/m(2). The targeted glucose level was 110-150 mg/dL. Glycemic variability was calculated as the standard deviation, glycemic lability index and coefficient of variation. Acquired infections were recorded using published consensus criteria for critically ill patients. Data analysis was on an intention-to-treat basis. Over a 2-year period, 157 patients were consecutively enrolled (A 52, B 53 and C 52). Compared with the standard control formula, the new formula gave rise to lower insulin requirement (19.1 ± 13.1 vs. 23.7 ± 40.1 IU/day, p pneumonia (p nutrition formula were produced on hospital stay or mortality. In these high-risk ICU patients, both diabetes-specific formulas lowered insulin requirements, improved glycemic control and reduced the risk of acquired infections relative to the standard formula. Compared with the control-specific formula, the new-generation formula also improved capillary glycemia. Clinicaltrials.gov NCT1233726 .

  18. Low-Level Laser and Light-Emitting Diode Therapy for Pain Control in Hyperglycemic and Normoglycemic Patients Who Underwent Coronary Bypass Surgery with Internal Mammary Artery Grafts: A Randomized, Double-Blind Study with Follow-Up.

    Science.gov (United States)

    Lima, Andréa Conceição Gomes; Fernandes, Gilderlene Alves; Gonzaga, Isabel Clarisse; de Barros Araújo, Raimundo; de Oliveira, Rauirys Alencar; Nicolau, Renata Amadei

    2016-06-01

    This study aimed to evaluate the efficacy of low-level laser therapy (LLLT) and light-emitting diodes (LEDs) for reducing pain in hyperglycemic and normoglycemic patients who underwent coronary artery bypass surgery with internal mammary artery grafts. This study was conducted on 120 volunteers who underwent elective coronary artery bypass graft (CABG) surgery. The volunteers were randomly allocated to four different groups of equal size (n = 30): control, placebo, LLLT [λ = 640 nm and spatial average energy fluence (SAEF) = 1.06 J/cm(2)], and LED (λ = 660 ± 20 nm and SAEF = 0.24 J/cm(2)). Participants were also divided into hyperglycemic and normoglycemic subgroups, according to their fasting blood glucose test result before surgery. The outcome assessed was pain during coughing by a visual analog scale (VAS) and the McGill Pain Questionnaire. The patients were followed for 1 month after the surgery. The LLLT and LED groups showed a greater decrease in pain, with similar results, as indicated by both the VAS and the McGill questionnaire (p ≤ 0.05), on the 6th and 8th postoperative day compared with the placebo and control groups. The outcomes were also similar between hyperglycemic and normoglycemic patients. One month after the surgery, almost no individual reported pain during coughing. LLLT and LED had similar analgesic effects in hyperglycemic and normoglycemic patients, better than placebo and control groups.

  19. EMG-force relation in the first dorsal interosseous muscle of patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jahanmiri-Nezhad, Faezeh; Hu, Xiaogang; Suresh, Nina L; Rymer, William Z; Zhou, Ping

    2014-01-01

    The relationship between surface electromyography (EMG) and muscle force is essential to assess muscle function and its deficits. However, few studies have explored the EMG-force relation in patients with amyotrophic lateral sclerosis (ALS). The purpose of this study was to examine the EMG-force relation in ALS subjects and its alteration in comparison with healthy control subjects. Surface EMG and force signals were recorded while 10 ALS and 10 age-matched healthy control subjects produced isometric voluntary contractions in the first dorsal interosseous (FDI) muscle over the full range of activation. A linear fit of the EMG-force relation was evaluated through the normalized root mean square error (RMSE) between the experimental and predicted EMG amplitudes. The EMG-force relation was compared between the ALS and the healthy control subjects. With a linear fit, the normalized RMSE between the experimental and predicted EMG amplitudes was 9.6 ± 3.6% for the healthy control subjects and 12.3 ± 8.0% for the ALS subjects. The slope of the linear fit was 2.9 ± 2.2 μVN-1 for the ALS subjects and was significantly shallower (p 0.05). A linear fit can be used to well describe the EMG-force relation for the FDI muscle of both ALS and healthy control subjects. A variety of processes may work together in ALS that can adversely affect the EMG-force relation.

  20. [Clinical presentation of a dorsal epidural arachnoid cyst after an epidural anesthesia].

    Science.gov (United States)

    Obil-Chavarría, Claudia Alejandra; García-Ramos, Carla Lisette; Castro-Quiñonez, Sergio Alberto; Huato-Reyes, Raúl; Santillán-Chapa, Concepción Guadalupe; Reyes-Sánchez, Alejandro Antonio

    Arachnoid cysts are dural diverticula with liquid content similar to cerebrospinal fluid, with 1% occurring in the spinal cord. They locate mainly in the dorsal region of the thoracic spine, and are unusual causes of spinal cord compression. The case is presented of a previously healthy 15-year-old boy, with a 20-month history of spastic paraparesis that started apparently after epidural block for ankle osteosynthesis. There was decreased sensitivity and strength of the pelvic limbs and gradually presented with anaesthesia from T12 to L4 dermatomes, L5 and S1 bilateral hypoaesthesia and 4+/5 bilateral strength, in the L2 root and 2+/5 in L3, L4, L5, S1, hyperreflexia, Babinski and clonus, but with no alteration in the sacral reflexes. In the magnetic resonance it was diagnosed as an extradural arachnoid cyst from T6 to T9. The patient underwent a T6 to T10 laminotomy, cyst resection, dural defect suture, and laminoplasty. One year after surgery, the patient had recovered sensitivity, improvement of muscle strength up to 4+/5 in L2 to S1, and normal reflexes. After the anaesthetic procedure, increased pressure and volume changes within the cyst could cause compression of the spinal cord, leading to symptoms. Despite being a long-term compression, the patient showed noticeable improvement. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  1. Dorsal scapular nerve neuropathy: a narrative review of the literature.

    Science.gov (United States)

    Muir, Brad

    2017-08-01

    The purpose of this paper is to elucidate this little known cause of upper back pain through a narrative review of the literature and to discuss the possible role of the dorsal scapular nerve (DSN) in the etiopathology of other similar diagnoses in this area including cervicogenic dorsalgia (CD), notalgia paresthetica (NP), SICK scapula and a posterolateral arm pain pattern. Dorsal scapular nerve (DSN) neuropathy has been a rarely thought of differential diagnosis for mid scapular, upper to mid back and costovertebral pain. These are common conditions presenting to chiropractic, physiotherapy, massage therapy and medical offices. The methods used to gather articles for this paper included: searching electronic databases; and hand searching relevant references from journal articles and textbook chapters. One hundred-fourteen articles were retrieved. After removing duplicates, there were 57 articles of which 29 were retrieved. There were 26 articles and textbook chapters retrieved by hand searching equaling 55 articles retrieved of which 47 relevant articles were used in this report. The anatomy, pathway and function of the dorsal scapular nerve can be varied and exceptionally rarely may include a sensory component. The signs and symptoms, therefore, may include pain, atrophy, scapular winging, and dysesthesia. The mechanism of injury to the DSN is also quite varied ranging from postural to overuse in overhead work and sport. Other conditions in this area, including CD, NP, SICK scapula and a posterolateral arm pain pattern bear a striking resemblance to DSN neuropathy. DSN neuropathy should be included in the list of common differential diagnoses of upper and mid-thoracic pain, stiffness, dysesthesia and dysfunction. The study also brings forward interesting connections between DSN neuropathy, CD, NP, SICK scapula and a posterolateral arm pain pattern.

  2. Dorsal hand coverage with free serratus fascia flap

    DEFF Research Database (Denmark)

    Fotopoulos, Peter; Holmer, Per; Leicht, Pernille

    2003-01-01

    In reconstructing a defect on the dorsum of the hand, with the extensor tendons exposed or even missing, functional, as well as cosmetic, goals are of major importance. The authors present three cases of extensor tendon reconstruction, combined with soft-tissue reconstruction, with the free...... in the flap, leaving the long thoracic nerve intact on the serratus muscle. Coverage of the flap with split-thickness skin graft is done immediately. The free serratus fascia flap is an ideal flap for dorsal hand coverage when the extensor tendons are exposed, especially because of low donor-site morbidity....

  3. Congenital dorsal urethral diverticulum: A rare case report

    Directory of Open Access Journals (Sweden)

    Samir Gupta

    2006-01-01

    Full Text Available Urethral diverticulum in males can be congenital or acquired (secondry to stricture, stenosis. Congenital urethral diverticulae of male urethra are rare. Most of them occur ventral to the native urethra, arising from the cystic dilatation of the Cowper′s gland ducts. Ours is the report of urethral diverticulum, which was present on the dorsal side of the urethra, with splaying of the two corpora cavernosa and thinning of the corpus spongiosum. The diverticulum was excised and urethroplasty was done. Postoperatively there was a marked improvement in the symptoms, with good cosmesis

  4. Covering the Dorsal Finger Defect with Reverse Cross Finger Flap

    Directory of Open Access Journals (Sweden)

    Kaan Gurbuz

    2014-12-01

    Full Text Available Reconstruction of finger extensor zone defects with or without tendon gaps still remains a challenge for surgeons. Although surgical treatments may differ, and range from the use of local, regional, to free flaps, the outcomes for all cases are not satisfactory. In this case report, we present a case of a 3rd finger extensor side crush injury including a defect of Dd (Digit Dorsal 1, Dd2 and Dd3 defects of extensor zones with tendon gap. Tendon gap was reconstructed using m. palmaris longus tendon graft and the defect was covered with reversed cross-finger flap (random pattern with good cosmetic and excellent functional results.

  5. The dorsal anterior cingulate cortex modulates dialectical self-thinking

    OpenAIRE

    Fei eWang; Kaiping ePeng; Yang eBai; Rui eLi; Ying eZhu; Pei eSun; Hua eGuo; Chun eYuan; Pia eRotshtein; Jie eSui

    2016-01-01

    Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here, we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgme...

  6. Dorsal dimelia in patau syndrome: a case report.

    Science.gov (United States)

    Fattah, A; Pickford, M A

    2007-10-01

    We present a case of a child with Patau syndrome that exhibits features consistent with congenital palmar nail syndrome. The literature is reviewed and evidence presented to demonstrate that this is a defect in the dorso-ventral patterning of the limb and thus a form of dorsal dimelia. In order to differentiate this from other instances of ectopic nail tissue we suggest congenital palmar nail syndrome should be more specifically defined as duplicated nails, absent flexion creases, non-glabrous skin on the palmar surface, reduced movement at the interphalangeal joints and hypoplastic terminal phalanges.

  7. Rooting plant development

    NARCIS (Netherlands)

    Scheres, B.

    2013-01-01

    In 1993, we published a paper in Development detailing the anatomical structure of the Arabidopsis root. The paper described how root growth was maintained by the precisely tuned activity of a small set of 'initials', which acted as the source of dividing and differentiating cells, and how these

  8. Anti-obesity and anti-hyperglycemic effects of cinnamaldehyde via altered ghrelin secretion and functional impact on food intake and gastric emptying.

    Science.gov (United States)

    Camacho, Susana; Michlig, Stephanie; de Senarclens-Bezençon, Carole; Meylan, Jenny; Meystre, Julie; Pezzoli, Maurizio; Markram, Henry; le Coutre, Johannes

    2015-01-21

    Cinnamon extract is associated to different health benefits but the active ingredients or pathways are unknown. Cinnamaldehyde (CIN) imparts the characteristic flavor to cinnamon and is known to be the main agonist of transient receptor potential-ankyrin receptor 1 (TRPA1). Here, expression of TRPA1 in epithelial mouse stomach cells is described. After receiving a single-dose of CIN, mice significantly reduce cumulative food intake and gastric emptying rates. Co-localization of TRPA1 and ghrelin in enteroendocrine cells of the duodenum is observed both in vivo and in the MGN3-1 cell line, a ghrelin secreting cell model, where incubation with CIN up-regulates expression of TRPA1 and Insulin receptor genes. Ghrelin secreted in the culture medium was quantified following CIN stimulation and we observe that octanoyl and total ghrelin are significantly lower than in control conditions. Additionally, obese mice fed for five weeks with CIN-containing diet significantly reduce their cumulative body weight gain and improve glucose tolerance without detectable modification of insulin secretion. Finally, in adipose tissue up-regulation of genes related to fatty acid oxidation was observed. Taken together, the results confirm anti-hyperglycemic and anti-obesity effects of CIN opening a new approach to investigate how certain spice derived compounds regulate endogenous ghrelin release for therapeutic intervention.

  9. Putative pacemakers in the eyestalk and brain of the crayfish Procambarus clarkii show circadian oscillations in levels of mRNA for crustacean hyperglycemic hormone.

    Directory of Open Access Journals (Sweden)

    Janikua Nelson-Mora

    Full Text Available Crustacean hyperglycemic hormone (CHH synthesizing cells in the optic lobe, one of the pacemakers of the circadian system, have been shown to be present in crayfish. However, the presence of CHH in the central brain, another putative pacemaker of the multi-oscillatory circadian system, of this decapod and its circadian transcription in the optic lobe and brain have yet to be explored. Therefore, using qualitative and quantitative PCR, we isolated and cloned a CHH mRNA fragment from two putative pacemakers of the multi-oscillatory circadian system of Procambarus clarkii, the optic lobe and the central brain. This CHH transcript synchronized to daily light-dark cycles and oscillated under dark, constant conditions demonstrating statistically significant daily and circadian rhythms in both structures. Furthermore, to investigate the presence of the peptide in the central brain of this decapod, we used immunohistochemical methods. Confocal microscopy revealed the presence of CHH-IR in fibers and cells of the protocerebral and tritocerebal clusters and neuropiles, particularly in some neurons located in clusters 6, 14, 15 and 17. The presence of CHH positive neurons in structures of P. clarkii where clock proteins have been reported suggests a relationship between the circadian clockwork and CHH. This work provides new insights into the circadian regulation of CHH, a pleiotropic hormone that regulates many physiological processes such as glucose metabolism and osmoregulatory responses to stress.

  10. Chromatic roots and hamiltonian paths

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2000-01-01

    We present a new connection between colorings and hamiltonian paths: If the chromatic polynomial of a graph has a noninteger root less than or equal to t(n) = 2/3 + 1/3 (3)root (26 + 6 root (33)) + 1/3 (3)root (26 - 6 root (33)) = 1.29559.... then the graph has no hamiltonian path. This result...

  11. The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn.

    Science.gov (United States)

    Abraira, Victoria E; Kuehn, Emily D; Chirila, Anda M; Springel, Mark W; Toliver, Alexis A; Zimmerman, Amanda L; Orefice, Lauren L; Boyle, Kieran A; Bai, Ling; Song, Bryan J; Bashista, Karleena A; O'Neill, Thomas G; Zhuo, Justin; Tsan, Connie; Hoynoski, Jessica; Rutlin, Michael; Kus, Laura; Niederkofler, Vera; Watanabe, Masahiko; Dymecki, Susan M; Nelson, Sacha B; Heintz, Nathaniel; Hughes, David I; Ginty, David D

    2017-01-12

    The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Predicting early reading skills from pre-reading measures of dorsal stream functioning.

    Science.gov (United States)

    Kevan, Alison; Pammer, Kristen

    2009-12-01

    It is well documented that good reading skills may be dependent upon adequate dorsal stream processing. However, the degree to which dorsal stream deficits play a causal role in reading failure has not been established. This study used coherent motion and visual frequency doubling to examine whether dorsal stream sensitivity measured before the commencement of formal reading instruction can predict emerging literacy skills in Grade 1. We demonstrate that over age, IQ and Kindergarten Letter knowledge, pre-reading measures of dorsal stream functioning, as assessed by frequency doubling sensitivity, could predict early literacy skills. These findings suggest that the relationship between dorsal stream functioning and poor reading skills exists before children learn to read, strengthening the claim that dorsal stream deficits may play a contributing role in reading failure.

  13. Agenesis of the dorsal pancreas and its association with pancreatic tumors.

    Science.gov (United States)

    Sakpal, Sujit Vijay; Sexcius, Lucretia; Babel, Nitin; Chamberlain, Ronald Scott

    2009-05-01

    Morphogenesis of the pancreas is a complex process; nevertheless, congenital anomalies are rare. At embryogenesis, the pancreas develops from the endoderm-lined dorsal and ventral buds of the duodenum. The ventral bud gives rise to the lower head and uncinate process of the pancreas; whereas, the dorsal bud gives rise to the upper head, isthmus, body, and tail of the pancreas. Rarely, developmental failure of the dorsal pancreatic bud at embryogenesis results in the agenesis of the dorsal pancreas--neck, body, and tail. Even rarer is the association of pancreatic tumors with agenesis of the dorsal pancreas. In addition to citing our case, we provide a comprehensive review on agenesis of the dorsal pancreas and its association with pancreatic tumors.

  14. Dorsale Internet ouverte en République démocratique du Congo ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    En ce qui concerne la RDC, les participants ont retenu les trois priorités suivantes: la dorsale nationale, les réseaux urbains et le parc informatique. La dorsale nationale a été jugée priorité numéro un. Ce projet vise à faire une étude de faisabilité portant sur la mise en place d'une dorsale Internet nationale en RDC.

  15. Core promoter functions in the regulation of gene expression of Drosophila dorsal target genes.

    Science.gov (United States)

    Zehavi, Yonathan; Kuznetsov, Olga; Ovadia-Shochat, Avital; Juven-Gershon, Tamar

    2014-04-25

    Developmental processes are highly dependent on transcriptional regulation by RNA polymerase II. The RNA polymerase II core promoter is the ultimate target of a multitude of transcription factors that control transcription initiation. Core promoters consist of core promoter motifs, e.g. the initiator, TATA box, and the downstream core promoter element (DPE), which confer specific properties to the core promoter. Here, we explored the importance of core promoter functions in the dorsal-ventral developmental gene regulatory network. This network includes multiple genes that are activated by different nuclear concentrations of Dorsal, an NFκB homolog transcription factor, along the dorsal-ventral axis. We show that over two-thirds of Dorsal target genes contain DPE sequence motifs, which is significantly higher than the proportion of DPE-containing promoters in Drosophila genes. We demonstrate that multiple Dorsal target genes are evolutionarily conserved and functionally dependent on the DPE. Furthermore, we have analyzed the activation of key Dorsal target genes by Dorsal, as well as by another Rel family transcription factor, Relish, and the dependence of their activation on the DPE motif. Using hybrid enhancer-promoter constructs in Drosophila cells and embryo extracts, we have demonstrated that the core promoter composition is an important determinant of transcriptional activity of Dorsal target genes. Taken together, our results provide evidence for the importance of core promoter composition in the regulation of Dorsal target genes.

  16. Localization of NADPH-diaphorase containing neurons in the spinal dorsal horn and spinal sensory ganglia of the turtle Chrysemys d'orbigny.

    Science.gov (United States)

    Radmilovich, M; Fernández, A; Trujillo-Cenóz, O

    1997-03-01

    NADPH-diaphorase positive (NDP) neurons and nerve fibers were found in the spinal dorsal horn (DH) and sensory ganglia of the turtle Chrysemys d'orbigny. Three well-defined types of NDP neurons were found in the DH: (a) elongated nerve cells with two radially arranged dendritic branches, (b) neurons with rostrocaudal dendritic branches, (c) bitufted neurons with two, practically symmetric branches that project to the ipsilateral and contralateral dorsal horns. A combination of the techniques that reveal NADPH-diaphorase activity with the horseradish peroxidase transganglionic labeling of the dorsal root collaterals, suggested that NDP neurons of the DH are second-order cells of the spinal sensory pathway. NDP neurons were also found in the spinal sensory ganglia at all metameric levels. Our findings indicate that the DH of turtles, like that of mammals, contains both the enzymatic machinery and the neural connections required to postulate the participation of nitric oxide in "plastic phenomena" such as hyperalgesia and central sensitization. Two other alternatives or complementary hypotheses are discussed: (a) NDP neurons in the DH and sensory ganglia may represent specific cell populations involved in the processing of sensory visceral information; (b) NADPH-diaphorase reactivity may indicate sustained levels of neuronal activity.

  17. ROOT User Workshop 2013

    CERN Document Server

    2013-01-01

    Since almost two decades, ROOT has established itself as the framework for HENP data processing and analysis. The LHC upgrade program and the new experiments being designed at CERN and elsewhere will pose even more formidable challenges in terms of data complexity and size. The new parallel and heterogeneous computing architectures that are either announced or already available will call for a deep rethinking of the code and the data structures to be exploited efficiently. This workshop, following from a successful series of such events, will allow you to learn in detail about the new ROOT 6 and will help shape the future evolution of ROOT.

  18. Network profiles of the dorsal anterior cingulate and dorsal prefrontal cortex in schizophrenia during hippocampal-based associative memory

    Directory of Open Access Journals (Sweden)

    Eric eWoodcock

    2016-04-01

    Full Text Available Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n=12 and healthy control subjects (n=10 participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC and the dorsal anterior cingulate cortex (dACC as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance with seed (dPFC vs. dACC, group (patients vs. controls, and memory process (encoding vs. retrieval as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness’ characterization as a disconnection syndrome.

  19. Network Profiles of the Dorsal Anterior Cingulate and Dorsal Prefrontal Cortex in Schizophrenia During Hippocampal-Based Associative Memory.

    Science.gov (United States)

    Woodcock, Eric A; Wadehra, Sunali; Diwadkar, Vaibhav A

    2016-01-01

    Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC) and the dorsal anterior cingulate cortex (dACC) as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance (ANOVA) with seed (dPFC vs. dACC), group (patients vs. controls), and memory process (encoding and retrieval) as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness' characterization as a disconnection syndrome.

  20. Neurogenic contraction and relaxation of human penile deep dorsal vein

    Science.gov (United States)

    Segarra, Gloria; Medina, Pascual; Domenech, Cristina; Martínez León, Juan B; Vila, José M; Aldasoro, Martin; Lluch, Salvador

    1998-01-01

    The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin.Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents.Electrical field stimulation (0.5–2 Hz) and noradrenaline (3×10−10–3×10−5 M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10−4 M) increased the adrenergic responses only in rings with endothelium.In preparations contracted with noradrenaline in the presence of guanethidine (10−6 M) and atropine (10−6 M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3×10−5 M) and tetrodotoxin (10−6 M), but was unaffected by removal of endothelium.Acetylcholine (10−8–3×10−5 M) and substance P (3×10−11–3×10−7 M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10−9–3×10−5 M) and papaverine (10−8–3×10−5 M) caused endothelium-independent relaxations.The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence. PMID:9690872

  1. Barbagli's dorsal urethroplasty. Analysis of results and factors for success.

    Science.gov (United States)

    Marchal, Cristobal; Pérez, Juan Enrique; Herrera, Bernardo; Saez, Felipe; Castillo, Elisabeth; Antuña, Francisco; Julve, Emilio; Machuca, Francisco Javier

    2010-09-01

    Dorsal urethroplasty as described by Barbagli has gained wide acceptance in the treatment of urethral stricture, given the simplification afforded by obtaining a free graft versus a flap. We present a series of 50 patients treated in our department of urethral stricture by dorsal onlay free graft urethroplasty (Barbagli's technique), in combination or not to other techniques in more complex strictures. The average age of patients was 48.8 years (23-77), the mean follow up 42.9 months (12-96) and the most frequently observed etiology has been the inflammatory urethral stricture (50%). Overall success rate was 82% (41 cases) and failure 18% (9 cases). In the longer follow-up group, there was a slight drop in success rate of 80% (24 cases) without any significant differences between groups (p= 0.9). Analyzing the variables length of free graft (p= 0.50, p> 36= 0.53), age (p= 0.12, p>36= 0.59), etiology of stricture (p= 0.77, p>36 = 0.77) and type of graft used (p=0.24, p>36= 0.38) did not show any influence on the final outcome of surgery, both in the total sample and the subgroup with follow-up > 36 months. The location of the stricture in bulbar urethra has shown better functional outcome than those operated on for strictures affecting also other urethral locations (p= 0.001) maintaining that result in the group of longer follow up (p>36= 0,001). The lack of treatment prior to urethral surgery has influenced the success of it, since 90.6% of patients without prior treatment before urethroplasty have seen a good functional outcome, compared to treatment prior to surgery that obtained a 66.7% (p= 0.03). This significance is also demonstrated in the group of follow-up > 36 months (p>36= 0.01). The dorsal onlay free graft urethroplasty is a versatile and reproducible technique with acceptable results which allows combination with other techniques when the stenosis extends to the penile urethra. In exceptional cases of panurethral strictures secondary to lichen sclerosus

  2. Genetic association among root morphology, root quality and root yield in ashwagandha (Withania somnifera

    Directory of Open Access Journals (Sweden)

    Kumar Ramesh R.

    2011-01-01

    Full Text Available Ashwagandha (Withania somnifera is a dryland medicinal crop and roots are used as valuable drug in traditional systems of medicine. Morphological variants (morphotypes and the parental populations were evaluated for root - morphometric, quality and yield traits to study genetic association among them. Root morphometric traits (root length, root diameter, number of secondary roots/ plant and crude fiber content exhibited strong association among them and showed significant positive genotypic correlation with yield. Starch-fiber ratio (SFR, determinant of brittle root texture showed strong negative association with root yield. The total alkaloid content had positive genotypic correlation with root yield. So genetic upgradation should aim at optimum balance between two divergent groups of traits i.e. root yield traits (root morphometric traits and crude fiber content and root textural quality traits (starch content and SFR to develop superior genotypes with better yield and quality.

  3. Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation

    Science.gov (United States)

    Matthews, Gillian A.; Nieh, Edward H.; Vander Weele, Caitlin M.; Halbert, Sarah A.; Pradhan, Roma V.; Yosafat, Ariella S.; Glober, Gordon F.; Izadmehr, Ehsan M.; Thomas, Rain E.; Lacy, Gabrielle D.; Wildes, Craig P.; Ungless, Mark A.; Tye, Kay M.

    2016-01-01

    Summary The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PaperClip PMID:26871628

  4. [Dorsal medulla oblongata stroke after a wasp sting].

    Science.gov (United States)

    Taurin, G; Canneva-Bourel, M L; Delafosse, J-M; Poirier, J; Merienne, M

    2006-03-01

    Although wasp stings can cause local reactions such as pain, flare, edema, swelling and severe reactions, including anaphylaxis; neurological vascular complications are rare. We report a case of a 36-year-old male who developed focal neurological symptoms after a wasp sting. The brain MRI showed an infarct in the left dorsal medulla. The blood test has showed an elevated level of venom-specific IgE antibodies and the skin test with wasp venom was highly positive. Improvement occurred rapidly after treatment with methylprednisone. The postulated mechanisms include vasoconstriction and platelet aggregation secondary to an injection of distinct allergens contained in wasp venom. It would thus be important to ask patients about any recent wasp sting, in order to provide appropriate treatment.

  5. Spinal dorsal horn astrocytes: New players in chronic itch

    Directory of Open Access Journals (Sweden)

    Makoto Tsuda

    2017-01-01

    Full Text Available Chronic itch is a debilitating symptom of inflammatory skin conditions, such as atopic dermatitis, and systemic diseases, for which existing treatment is largely ineffective. Recent studies have revealed the selective neuronal pathways that are involved in itch sensations; however, the mechanisms by which itch turns into a pathological chronic state are poorly understood. Recent advances in our understanding of the mechanisms producing chronic itch have been made by defining causal roles for astrocytes in the spinal dorsal horn in mouse models of chronic itch including atopic dermatitis. Understanding the key roles of astrocytes may provide us with exciting insights into the mechanisms for itch chronicity and lead to a previously unrecognized target for treating chronic itch.

  6. Functional specialization in dorsal and ventral premotor areas.

    Science.gov (United States)

    Hoshi, Eiji; Tanji, Jun

    2004-01-01

    The premotor cortex (PM) in the bilateral lateral hemisphere of nonhuman primates and the human has been implicated in the sensorial guidance of movements. This is in contrast to more medial motor areas that are involved more in the temporal structuring of movements based on memorized information. The PM is further subdivided into dorsal (PMd) and ventral (PMv) parts. In this chapter, we describe our attempts to find differences in the use of these two areas in a nonhuman primate for programming future motor actions based on visual signals. We show that neurons in the PMv are involved primarily in receiving visuospatial signals and in specifying the spatial location of the target to be reached. In contrast, neurons in the PMd are involved more in integrating information about which arm to use and the target to be reached. Thus, PMd neurons are more implicated than those of the PMv in the preparation for a future motor action.

  7. [The crooked nose: correction of dorsal and caudal septal deviations].

    Science.gov (United States)

    Foda, H M T

    2010-09-01

    The deviated nose represents a complex cosmetic and functional problem. Septal surgery plays a central role in the successful management of the externally deviated nose. This study included 800 patients seeking rhinoplasty to correct external nasal deviations; 71% of these suffered from variable degrees of nasal obstruction. Septal surgery was necessary in 736 (92%) patients, not only to improve breathing, but also to achieve a straight, symmetric external nose. A graduated surgical approach was adopted to allow correction of the dorsal and caudal deviations of the nasal septum without weakening its structural support to the nasal dorsum or nasal tip. The approach depended on full mobilization of deviated cartilage, followed by straightening of the cartilage and its fixation in the corrected position by using bony splinting grafts through an external rhinoplasty approach.

  8. Gravisensitivity of cress roots

    Science.gov (United States)

    Volkmann, Dieter; Tewinkel, Martin

    The minimum dose (stimulus x time [gs]) eliciting a visible gravitropic response, has been determined using continuous and intermittent stimulation and two different accelerations at 1g and 0.1g. The minimum dose of 20 - 30 gs estimated for microgravity roots and of 50 - 60 gs for roots grown on a 1g-centrifuge indicated a higher sensitivity of microgravity roots. Applying intermittent stimuli to microgravity-grown roots, gravitropic responses were observed after two stimuli of 13.5 gs separated by a stimulus free interval of 118 s. The curvature of microgravity-grown roots to lateral stimulation by 0.1 g was remarkably smaller than by 1g in spite of the same doses which were applied to the seedlings. Microscopic investigations corresponding to stimulations in the range of the threshold values, demonstrated small displacement (< 2 μm) of statoliths in root statocytes. Accepting the statolith theory, one can conclude that stimulus transformation has to occur in the cytoplasm in close vicinity to the statoliths and that this transformation system was affected during seedling cultivation in microgravity.

  9. Selective resection of dorsal nerves of penis for premature ejaculation.

    Science.gov (United States)

    Zhang, G-X; Yu, L-P; Bai, W-J; Wang, X-F

    2012-12-01

    Premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions. Selective resection of the dorsal nerve (SRDN) of penis has recently been used for the treatment of PE and has shown some efficacy. To further clarify the efficacy and safety of SRDN on PE, we performed a preliminary, randomized, placebo-controlled clinical observational study. Persons with the complaints of rapid ejaculation, asking for circumcision because of redundant foreskin, intravaginal ejaculation latency time (IELT) within 2 min, not responding to antidepressant medication or disliking oral medication were randomly enrolled in two groups. From April 2007 to August 2010, a total of 101 eligible persons were enrolled, 40 of them received SRDN which dorsal nerves of the penis were selectively resected, and those (n = 61) enrolled in the control group were circumcised only. IELT and the Brief Male Sexual Function Inventory (BMSFI) questionnaire were implemented pre- and post-operatively for the evaluation of the effect and safety of the surgery. There are no statistically significant differences in the baseline data including mean ages, mean IELTs, perceived control abilities and the BMSFI mean scores between the two groups. With regard to the post-operative data of the surgery, both IELTs and perceived control abilities were significantly increased after SRDN (1.1 ± 0.9 min vs. 3.8 ± 3.1 min for pre- and post-operative IELT, respectively, p 0.05). Also, there were no statistically significant differences both in BMSFI composite and subscale scores between the two groups after surgery. Hence, we conclude that SRDN is effective in delaying ejaculation and improving ejaculatory control, whereas erectile function is not affected. The results imply that SRDN may be an alternative method for the treatment of PE for some patients. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

  10. The Effect of Honey on Plasma Malondialdehyde (MDA Level onAlloxan-Induced hyperglycemic Rats An Experimental studies in rats Galur Wistar White Males

    Directory of Open Access Journals (Sweden)

    Bela Risqiyani Fajrilah

    2013-12-01

    Full Text Available Malondialdehyde (MDA is the end product of lipid peroxidation and a marker of free radicals. Honey is a safe sweetener proven to lower blood glucose level and contains flavonoids, vitamin A, C, E as a source of antioxidant that can capture free radicals. This study aims to determine the effect of honey on plasma MDA level ionalloxan-induced hyperglycemicrats. This was an experimental study with post-test only control group design conducted for 25 days using 18 white male Wistar rats divided into 3 groups randomly. A negative control group, group B were given honey orally at the dose of 0.54 ml/mice/day, and group C were given honey orally at the of dose 0.9 ml/head/day. Each group consisted of 6 rats. Blood plasma MDA was evaluated by Thiobarbituric Acid Reactive Substance (TBARS test assay. One way ANOVA analysis test followed post hoc were applied for data analysis. The results showed that mean levels of MDA in group A, B, and C were 6.02 mmol/l ± 0.36, 4.37 mmol/± 0.30, and 1.12 mmol/l ± 0.11 respectively. Bivariate analysis One way ANOVA test showed a significant difference (p<0,05. Post hoc tests showed a significant differences between the study groups (p<0,05. It can be concluded that honey had an effect on the levels of malondialdehyde (MDA in the blood plasma of alloxan-induced hyperglycemic rats.

  11. Effect of amyloid-Β (25-35) in hyperglycemic and hyperinsulinemic rats, effects on phosphorylation and O-GlcNAcylation of tau protein.

    Science.gov (United States)

    Lozano, Liliana; Guevara, Jorge; Lefebvre, Tony; Ramos-Martinez, Ivan; Limón, Daniel; Díaz, Alfonso; Cerón, Eduarda; Zenteno, Edgar

    2017-06-01

    Aggregation of the amyloid beta (Aβ) peptide and hyperphosphorylation of tau protein, which are markers of Alzheimer's disease (AD), have been reported also in diabetes mellitus (DM). One regulator of tau phosphorylation is O-GlcNAcylation, whereas for hyperphosphorylation it could be GSK3beta, which is activated in hyperglycemic conditions. With this in mind, both O-GlcNAcylation and phosphorylation of tau protein were evaluated in the brain of rats with streptozotocin (STZ)-induced hyperglycemia and hyperinsulinemia and treated with the Aß25-35 peptide in the hippocampal region CA1. Weight, glycated hemoglobin, glucose, and insulin were determined. Male Wistar rats were divided in groups (N=20): a) control, b) treated only with the Aβ25-35 peptide, c) treated with Aβ25-35 and STZ, and d) treated only with STZ. Results showed statistically significant differences in the mean weight, glucose levels, insulin concentration, and HbA1c percentage, between C- and D-treated groups and not STZ-treated A and B (P<0.05). Interestingly, our results showed diminution of O-GlcNAcylation and increase in P-tau-Ser-396 in the hippocampal area of the Aβ25-35- and STZ-treated groups; moreover, enhanced expression of GSK3beta was observed in this last group. Our results suggest that hyperinsulinemia-Aβ25-35-hyperglycemia is relevant for the down regulation of O-GlcNAcylation and up-regulation of the glycogen synthase kinase-3 beta (GSK3beta), favoring Aβ25-35-induced neurotoxicity in the brain of rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Minimally processed foods are more satiating and less hyperglycemic than ultra-processed foods: a preliminary study with 98 ready-to-eat foods.

    Science.gov (United States)

    Fardet, Anthony

    2016-05-18

    Beyond nutritional composition, food structure is increasingly recognized to play a role in food health potential, notably in satiety and glycemic responses. Food structure is also highly dependent on processing conditions. The hypothesis for this study is, based on a data set of 98 ready-to-eat foods, that the degree of food processing would correlate with the satiety index (SI) and glycemic response. Glycemic response was evaluated according to two indices: the glycemic index (GI) and a newly designed index, the glycemic glucose equivalent (GGE). The GGE indicates how a quantity of a certain food affects blood glucose levels by identifying the amount of food glucose that would have an effect equivalent to that of the food. Then, foods were clustered within three processing groups based on the international NOVA classification: (1) raw and minimally processed foods; (2) processed foods; and (3) ultra-processed foods. Ultra-processed foods are industrial formulations of substances extracted or derived from food and additives, typically with five or more and usually many (cheap) ingredients. The data were correlated by nonparametric Spearman's rank correlation coefficient on quantitative data. The main results show strong correlations between GGE, SI and the degree of food processing, while GI is not correlated with the degree of processing. Thus, the more food is processed, the higher the glycemic response and the lower its satiety potential. The study suggests that complex, natural, minimally and/or processed foods should be encouraged for consumption rather than highly unstructured and ultra-processed foods when choosing weakly hyperglycemic and satiating foods.

  13. Dorsal arthrodesis in prepubertal New Zealand white rabbits followed to skeletal maturity: Effect on thoracic dimensions, spine growth and neural elements

    Directory of Open Access Journals (Sweden)

    Canavese Federico

    2010-01-01

    Full Text Available Background: Several studies have shown that severe spinal deformity and early arthrodesis can adversely affect the development of the spine and thorax by changing their shape and reducing their normal function. This article analyzes the consequences of posterior fusion on the growth of spine, thorax and neural elements in New Zealand white rabbits and compares with similar human data. Materials and Methods : The first section of the article analyzes the consequences of T1-T6 dorsal arthrodesis on the growth of the spine, sternum, thorax volume and neural elements in 12 prepubertal female New Zealand white rabbits, through a study of CT scans and histology specimens. The second part, evaluates thoracic dimensions in 21 children with spinal arthrodesis for treatment of deformity performed prior to nine years of age. Results: Dorsal arthrodesis in prepubertal rabbits changes thoracic growth patterns. In operated rabbits thoracic depth grows more slowly than thoracic width. The sternum as well as length of thoracic vertebral bodies in the spinal segment T1-T6 show reduced growth. Children undergoing spinal arthrodesis before nine years of age were noted to have shortened height, short trunk and disproportionate body habitus at skeletal maturity. Observed spine height and chest dimension values were reduced compared to the expected norms. The ratio between chest width and chest depth was below normal values. Conclusions: The first part of the study shows that thoracic dorsal arthrodesis in prepubertal New Zealand white rabbit influences thoracic, spine growth and affects the shape of pseudo unipolar neurons of the dorsal root ganglia. The second part demonstrates that children treated before nine years of age have significantly reduced spine height and thoracic dimensions. The thorax becomes elliptical as chest depth grows less than chest width. Both experimental and clinical findings contribute to explain reduced chest growth and subsequent thoracic

  14. EXPRESS: Methylcobalamin ameliorates neuropathic pain induced by vincristine in rats: Effect on loss of peripheral nerve fibers and imbalance of cytokines in the spinal dorsal horn.

    Science.gov (United States)

    Xu, Jing; Wang, Wei; Zhong, Xiong-Xiong; Feng, Yiwei; Wei, Xuhong; Liu, Xian-Guo

    2016-01-01

    Vincristine, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and there are currently no effective drugs to prevent or treat this side effect. Previous studies have shown that methylcobalamin has potential analgesic effect in diabetic and chronic compression of dorsal root ganglion model; however, whether methylcobalamin has effect on vincristine-induced painful peripheral neuropathy is still unknown. We found that vincristine-induced mechanical allodynia and thermal hyperalgesia, accompanied by a significant loss of intraepidermal nerve fibers in the plantar hind paw skin and an increase in the incidence of atypical mitochondria in the sciatic nerve. Moreover, in the spinal dorsal horn, the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the protein expression of p-p65 as well as tumor necrosis factor a was increased, whereas the protein expression of IL-10 was decreased following vincristine treatment. Furthermore, intraperitoneal injection of methylcobalamin could dose dependently attenuate vincristine-induced mechanical allodynia and thermal hyperalgesia, which was associated with intraepidermal nerve fibers rescue, and atypical mitochondria prevalence decrease in the sciatic nerve. Moreover, methylcobalamin inhibited the activation of NADPH oxidase and the downstream NF-kB pathway. Production of tumor necrosis factor a was also decreased and production of IL-10 was increased in the spinal dorsal horn following methylcobalamin treatment. Intrathecal injection of Phorbol-12-Myristate-13-Acetate, a NADPH oxidase activator, could completely block the analgesic effect of methylcobalamin. Methylcobalamin attenuated vincrinstine-induced neuropathic pain, which was accompanied by inhibition of intraepidermal nerve fibers loss and mitochondria impairment. Inhibiting the activation of NADPH oxidase and the downstream NF-kB pathway, resulting in the rebalancing of proinflammatory and anti-inflammatory cytokines

  15. Phosphorylation of tyrosine receptor kinase B in the dorsal striatum and dorsal hippocampus is associated with response learning in a water plus maze.

    Science.gov (United States)

    Pahng, Amanda R; Colombo, Paul J

    2017-02-01

    The dorsal hippocampus and dorsal striatum have dissociable roles in learning and memory that are related to region-specific changes in proteins necessary for neuronal plasticity and memory formation. There is additional evidence that the hippocampus and striatum can interact during memory formation. Phosphorylation of tyrosine receptor kinase B is important for memory formation in the hippocampus, but whether or not it has a role in striatum-dependent learning, or in interactions between the hippocampus and striatum, has not been examined. In the present study, we tested the hypothesis that response training increases pTrkB in the dorsal striatum, but decreases pTrkB in dorsal hippocampus, due to an interaction between the systems during memory formation. Results show a significant decrease in pTrkB levels in the dorsal hippocampus of rats trained on the response task compared with swim controls. Response training did not increase pTrkB levels in the dorsal striatum. Positive correlations were found between response learning and the total area of cells expressing pTrkB in the dorsal striatum, while no correlations were found in swim controls. Our results partially support our hypothesis and indicate that response learning is associated with a decrease in hippocampal pTrkB, while phosphorylation of TrkB in the dorsal striatum remains constant. This indicates that suppression of hippocampal pTrkB during response learning may be involved in striatum-dependent memory formation. Additionally, our findings suggest that activation of TrkB in a sparse arrangement of cells may be associated with faster acquisition of a response task. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Root architecture impacts on root decomposition rates in switchgrass

    Science.gov (United States)

    de Graaff, M.; Schadt, C.; Garten, C. T.; Jastrow, J. D.; Phillips, J.; Wullschleger, S. D.

    2010-12-01

    Roots strongly contribute to soil organic carbon accrual, but the rate of soil carbon input via root litter decomposition is still uncertain. Root systems are built up of roots with a variety of different diameter size classes, ranging from very fine to very coarse roots. Since fine roots have low C:N ratios and coarse roots have high C:N ratios, root systems are heterogeneous in quality, spanning a range of different C:N ratios. Litter decomposition rates are generally well predicted by litter C:N ratios, thus decomposition of roots may be controlled by the relative abundance of fine versus coarse roots. With this study we asked how root architecture (i.e. the relative abundance of fine versus coarse roots) affects the decomposition of roots systems in the biofuels crop switchgrass (Panicum virgatum L.). To understand how root architecture affects root decomposition rates, we collected roots from eight switchgrass cultivars (Alamo, Kanlow, Carthage, Cave-in-Rock, Forestburg, Southlow, Sunburst, Blackwell), grown at FermiLab (IL), by taking 4.8-cm diameter soil cores from on top of the crown and directly next to the crown of individual plants. Roots were carefully excised from the cores by washing and analyzed for root diameter size class distribution using WinRhizo. Subsequently, root systems of each of the plants (4 replicates per cultivar) were separated in 'fine' (0-0.5 mm), 'medium' (0.5-1 mm) and 'coarse' roots (1-2.5 mm), dried, cut into 0.5 cm (medium and coarse roots) and 2 mm pieces (fine roots), and incubated for 90 days. For each of the cultivars we established five root-treatments: 20g of soil was amended with 0.2g of (1) fine roots, (2) medium roots, (3) coarse roots, (4) a 1:1:1 mixture of fine, medium and coarse roots, and (5) a mixture combining fine, medium and coarse roots in realistic proportions. We measured CO2 respiration at days 1, 3, 7, 15, 30, 60 and 90 during the experiment. The 13C signature of the soil was -26‰, and the 13C signature

  17. Recruitment of dorsal columm fibers in spinal cord stimulation: influence of collateral branching

    NARCIS (Netherlands)

    Struijk, J.J.; Struijk, Johannes J.; Holsheimer, J.; van der Heide, Gerlof G.; van der Heide, G.G.; Boom, H.B.K.

    1992-01-01

    An electrical network model of myelinated dorsal column nerve fibers is presented. The effect of electrical simulation was investigated using both a homogeneous volume conductor and a more realistic model of the spinal cord. An important feature of dorsal column nerve fibers is the presence of

  18. Nucleocytoplasmic shuttling mediates the dynamic maintenance of nuclear Dorsal levels during Drosophila embryogenesis

    DEFF Research Database (Denmark)

    DeLotto, Robert; DeLotto, Yvonne; Steward, Ruth

    2007-01-01

    In Drosophila, the NF-kappaB/REL family transcription factor, Dorsal, redistributes from the cytoplasm to nuclei, forming a concentration gradient across the dorsoventral axis of the embryo. Using live imaging techniques in conjunction with embryos expressing a chimeric Dorsal-GFP, we demonstrate...

  19. Role of the right dorsal anterior insula in the urge to tic in Tourette syndrome.

    Science.gov (United States)

    Tinaz, Sule; Malone, Patrick; Hallett, Mark; Horovitz, Silvina G

    2015-08-01

    The mid-posterior part of the insula is involved in processing bodily sensations and urges and is activated during tic generation in Tourette syndrome. The dorsal anterior part of the insula, however, integrates sensory and emotional information with cognitive valuation and is implicated in interoception. The right dorsal anterior insula also participates in urge suppression in healthy subjects. This study examined the role of the right dorsal anterior insula in the urge to tic in Tourette syndrome. Resting-state functional magnetic resonance imaging was performed in 13 adult Tourette patients and 13 matched controls. The role of the right dorsal anterior insula within the urge-tic network was investigated using graph theory-based neural network analysis. The functional connectivity of the right dorsal anterior insula was also correlated with urge and tic severity. Even though the patients did not exhibit any overt tics, the right dorsal anterior insula demonstrated higher connectivity, especially with the frontostriatal nodes of the urge-tic network in patients compared with controls. The functional connectivity between the right dorsal anterior insula and bilateral supplementary motor area also correlated positively with urge severity in patients. These results suggest that the right dorsal anterior insula is part of the urge-tic network and could influence the urge- and tic-related cortico-striato-thalamic regions even during rest in Tourette syndrome. It might be responsible for heightened awareness of bodily sensations generating premonitory urges in Tourette syndrome. © 2015 International Parkinson and Movement Disorder Society.

  20. The interaction between the locus coeruleus and dorsal raphe nucleus studied with dual-probe microdialysis

    NARCIS (Netherlands)

    Pudovkina, OL; Cremers, TIFH; Westerink, BHC

    2002-01-01

    The interaction between the locus coeruleus and dorsal raphe nucleus was investigated by means of dual-probe microdialysis in conscious rats. The release of noradrenaline and 5-hydroxytryptamine (5-HT) after inhibition or stimulation of locus cocruleus and dorsal raphe activity was sampled in both

  1. Pattern of hair distribution on the dorsal phalanges of the hand in ...

    African Journals Online (AJOL)

    Background: The distribution of hair in the dorsal aspect of the hand digits were investigated in this study. Aim: To determine dorsal phalengeal hair pattern in an African ethnic group. Methods: The study involved 160 male and 140 female of Urhobo volunteers whose ages ranged between 18 and 38 years. Results: Hair ...

  2. Effectiveness of selective dorsal rhizotomy in 2 patients with progressive spasticity due to neurodegenerative disease

    NARCIS (Netherlands)

    Grunt, Sebastian; van der Knaap, Marjo S.; van Ouwerkerk, Willem J. R.; Strijers, Rob L. M.; Becher, Jules G.; Vermeulen, R. Jeroen