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1
Baseer, Najma. "Spinal cord neuronal circuitry involving dorsal horn projection cells". Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5596/.
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The spinal cord dorsal horn is involved in the processing and transmission of sensory information to the brain. There are several distinct populations of dorsal horn projection cells that constitute the major output of the spinal cord. These cells are mostly found in lamina I and are scattered throughout the deep dorsal horn. There is a population of large lamina III projection cells that expresses the neurokinin 1 receptor (NK1r), which is the main target for substance P released by nociceptive primary afferents. These cells are densely innervated by peptidergic nociceptive afferents and more sparsely by low-threshold myelinated afferents. In addition, they also receive selective innervation from neuropeptide Y-containing inhibitory interneurons. However, not much is known about their input from glutamatergic spinal neurons. It has already been reported that the great majority of large lamina III NK1r expressing cells project to caudal ventrolateral medulla (CVLM) therefore in this study these cells were easily identified without retrograde tracer injection. Preliminary observations showed that these cells received contacts from preprodynorphin (PPD)-containing excitatory axons. The first part of the study tested the hypothesis that lamina III projection cells are selectively targeted by PPD-containing excitatory spinal neurons. Spinal cord sections from lumbar segments of the rat underwent immunocytochemical processing including combined confocal and electron microscopy to look for the presence of synapses at the sites of contact. The results showed that lamina III NK1r cells received numerous contacts from non-primary boutons that expressed vesicular glutamate transporter 2 (VGLUT2), and formed asymmetrical synapses on their dendrites and cell bodies. These synapses were significantly smaller than those formed by peptidergic afferents but provided a substantial proportion of the glutamatergic input to lamina III NK1r projection cells. Furthermore, it was observed that PPD was found to be present in ~58% of the VGLUT2 boutons that contacted these cells while a considerably smaller proportion of (5-7%) VGLUT2 boutons in laminae I-IV expressed PPD. These results indicate a highly selective targeting of the lamina III projection neurons by glutamatergic neurons that express PPD. Fine myelinated (Aδ) nociceptors are responsible for the perception of fast, well-localised pain. Very little is known about their postsynaptic targets in the spinal cord, and therefore about their roles in the neuronal circuits that process nociceptive information. In the second part of the study, Fluorogold injections were made into the lateral parabrachial region (LPb) of the rat brain on one side and cholera toxin B subunit (CTb) was injected into the sciatic nerve on the contralateral side to assess whether Aδ nociceptors provide input to lamina I projection cells. The vast majority of lamina I projection neurons belong to the spinoparabrachial tract, and these can be divided into two major groups: those that express NK1r, and those that do not. The results suggested that CTb labelled a distinct set of Aδ nociceptors, most of which lack neuropeptides. CTb-labelled Aδ afferents formed contacts on 43% of the spinoparabrachial lamina I neurons that lacked the NK1r, but on a significantly smaller proportion (26%) of NK1r projection cells. Combined confocal and electron microscopy established that the contacts were associated with synapses. Furthermore, the contact density of CTb labelled boutons was considerably higher on the NK1r- cells than on those with the NK1r. These results provide further evidence that primary afferents input to projection cells is organized in a specialized way and that both NK1r+ and NK1r- lamina I projection neurons are directly innervated by Aδ nociceptors, thus may have an important role in the perception of fast pain. Lamina I of the rat spinal cord dorsal horn contains a population of large spinoparabrachial projection neurons (giant cells) that receive numerous synapses from both excitatory (VGLUT2) and inhibitory (VGAT) interneurons. The giant cells are selectively innervated by GABAergic axons that express neuronal-nitric oxide synthase (nNOS) and are thought to originate from local inhibitory interneurons. In the rat, the nNOS inhibitory cells belong to a distinct functional population that differs from other inhibitory interneurons in terms of somatostatin receptor (sst2A) expression and also in responsiveness to painful stimuli. There is a population of inhibitory interneurons that express green fluorescent protein (GFP) in lamina II of mice in which GFP is under control of the prion promoter (PrP) and the great majority of these cells also express nNOS. In this part of the study, the inhibitory synaptic input from nNOS-containing GFP boutons to giant lamina I cells was investigated. The great majority of lamina I projection neurons express NK1 receptor; therefore, the possibility that lamina I NK1r-expressing projection neurons received innervation from GFP+/nNOS+ axons was also tested. Since retrograde tracing technique was not used in this part of the study, lamina I projection cells were identified based on the observations made in the previous studies in the rat. Lamina I giant cells were recognized with antibodies against glycine receptor associated protein gephyrin as well as VGLUT2 and VGAT boutons, all of which provide dense innervation to these cells while only those lamina I NK1cells were included in the sample that were large and strongly immunoreactive for NK1r. The results indicated that although GFP axons accounted for only 7-9% of the GABAergic boutons in superficial dorsal horn, they provided over 70% of the inhibitory synapses on most of the giant cells in the PrP-GFP mouse and the great majority of these boutons also contained nNOS. Moreover, a subset of large lamina I NK1r-expressing cells (18/60) received a substantial inhibitory input (> 30%) from GFP+ boutons while the majority of these neurons showed sparse (< 15%) synaptic input. Recently, it has been reported that loss of some inhibitory interneurons in mice lacking the transcription factor Bhlhb5 results in exaggerated itch, and the cells that are lost include many of those that would normally express nNOS. Therefore, in the final set of experiments was designed to test whether there is a reduction in the inhibitory synaptic input to the giant cells in Bhlhb5-/- mouse. Spinal cord sections from Bhlhb5-/- mice and the wild type littermates were processed and analysed to determine any difference in the inhibitory nNOS input to lamina I giant cells belonging to either group. The giant cells from the knockout mice showed a substantial reduction (~80%) in their inhibitory nNOS input; with a moderate reduction in their overall GABAergic input (~35%). There was a considerable increase in nNOS-/VGAT+ boutons in the Bhlhb5-/- mouse (18 ± 4.6 and 37.7 ± 8.2/100 µm of the dendrite in WT and KO, respectively), suggesting some compensation from other nNOS-negative inhibitory interneurons. These results suggest that the loss of nNOS-containing inhibitory synaptic input to lamina I projection cells may contribute to the abnormal scratching behaviour seen in the Bhlhb5-/- mouse. This raises the possibility that the giant cells and a subset of large lamina I NK1r-expressing cells are involved in perception of itch.
2
Lawson, Jeffrey J. "Encoding of periodic skin stimuli by spinal dorsal horn neurons". Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1654.
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Thesis (Ph. D.)--West Virginia University, 2000.Title from document title page. Document formatted into pages; contains ix, 140 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 123-137).
3
Jennings, Ernest Albert. "Cutaneous afferent evoked activity in the postnatal rat spinal cord". Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369052.
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4
Vu, Hung. "Mechanisms of rapid receptive field reorganization in rat spinal cord". Thesis, University of North Texas, 2002. https://digital.library.unt.edu/ark:/67531/metadc3197/.
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Rapid receptive field (RF) reorganization of somatosensory neurons in the rat dorsal horn was examined using extracellular single unit recording. Subcutaneous injection of lidocaine into RFs of dorsal horn neurons results in expansion of their RFs within minutes. The expanded RFs appear adjacent to or/and proximal to original RFs. Out of 63 neurons tested, 36 (58%) show RF reorganization. The data suggest that dorsal horn of spinal cord is one of the initial sites for RF reorganization. The neural mechanisms of this effect are not well understood. We propose that changes in biophysical properties (membrane conductance, length constant) of the neurons resulting from lidocaine injection contribute to RF reorganization. Iontophoretic application of glutamate onto dorsal horn neurons that show lidocaine induced RF's expansion were used to test the model. Application of glutamate produced reduction of reorganized RFs in 9 of 20 (45%) tested cells. Application of NBQX produced no effect on either original or expanded RFs indicate that RF shrinkage effects of glutamate involve NMDA receptors. The results are consistent with the prediction of the proposed model. Subcutaneous injection of capsaicin into tactile RFs of low threshold mechanoreceptive dorsal horn neurons produced no effect on the RF sizes that are consistent with other studies. Following the injection, the original RFs were completely silenced (46%) or remained responsive (54%).
5
Al, Ghamdi Kholoud Saad. "Populations of spinal cord dorsal horn neurons and their role in nociception". Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3425/.
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Nociception involves detection of tissue damage by specialized receptors; nociceptors. These convey information to the first synaptic relays in the dorsal horn of the spinal cord. Within the dorsal horn itself are the dorsal horn neurons which can be divided into two broad classes, based on their axonal projections: projection neurons and interneurons. The neurokinin 1 receptor (NK1r), the main target for substance P, is expressed by most projection neurons and many interneurons in the dorsal horn. These NK1r-expressing neurons show a bimodal size distribution in lamina I. The 1st part of the project tested the hypothesis that large NK1r-immunoreactive cells in this lamina are projection neurons, while the small cells are interneurons. Rats were anaesthetised and received injections of tracers into two supraspinal areas that are likely to label all contralateral lamina I projection neurons. The rats were re-anaesthetized and perfused 3 days later and 1341 NK1r-positive cells were analysed, of which 441 were retrogradely labelled. Cross-sectional soma areas of projection neurons were larger than those of cells that were not retrogradely labelled. This difference was highly significant. Nearly all (99.4%) of the NK1r-expressing cells that were not retrogradely labelled had soma areas <200 microm2, while only 9.8% of the retrogradely labelled NK1r-expressing cells had somata <200 microm2. These results provide a means of distinguishing lamina I NK1r-expressing projection neurons from interneurons based on their soma sizes without the need of retrograde tracing surgeries. Lamina I contains another population of projection neurons that lack or weakly express the NK1 receptor and consists of very large cells: giant cells, which are coated with the glycine and gamma-aminobutyric acid (GABA) receptor associated protein, gephyrin. There is also a group of large NK1r-expressing projection neurons with cell bodies in laminae III-IV and dendrites that pass dorsally to enter lamina I. Extracellular signal-regulated kinase (ERK) is expressed in dorsal horn neurons and is activated (phosphorylated) by noxious stimuli. In the 2nd part of the project, ERK phosphorylation in NK1r-expressing neurons as well as in lamina I giant cells was investigated following different type of noxious stimuli. Anaesthetised rats received noxious cutaneous, deep or visceral stimuli. They remained anaesthetized for 5 min after the end of the stimulus, and were then fixed by perfusion. Spinal cord sections were immunoreacted to reveal NK1r, gephyrin and phosphorylated ERK (pERK). Among the NK1r-expressing lamina I neurons, pERK was detected in both projection (somata >200 microm2) neurons and interneurons, with a significantly higher proportion in the larger cells, after all types of noxious stimulation. There was no significant difference in the frequency of pERK expression between the three morphological classes (fusiform, pyramidal and multipolar) of lamina I NK1r-expressing projection neurons after these stimuli. Most of the giant cells contained pERK after noxious cutaneous stimuli, but few did so following noxious deep stimulation. Only a few of laminae III-IV NK1r-expressing projection cells contained pERK after noxious deep or visceral stimulation, and the labelling in these was very weak. Results from the present study indicate that different types of neurons have different roles in conveying nociceptive information. The superficial dorsal horn (SDH) is also a vital area for modulating nociception and contains large number of excitatory and inhibitory interneurons. Glutamate, released by primary afferents and local excitatory neurons, acts on G-protein-coupled metabotropic glutamate receptors (mGlus). Group I mGlus (mGlu1 and mGlu5) are strongly expressed in the SDH. It has been reported that intrathecal administration of the mGlu1/5 agonist 3,5-dihydroxyphenylglycine (DHPG) induces spontaneous nociceptive behaviours, which are ERK-dependent. In the 3rd part of the project, ERK phosphorylation in mGlu5-expressing neurons following the administration of DHPG was investigated. Anaesthetized rats underwent a laminectomy procedure. DHPG or saline was applied to their exposed lumbar cord for 8 minutes after which they were perfused. Sections from the lumbar spinal cord were immunoreacted to reveal mGlu5, pERK and one of various markers for excitatory or inhibitory interneurons. Following DHPG (but not saline), numerous pERK-positive cells were seen in the SDH, particularly lamina II, and the great majority of these were mGlu5-positive. ERK phosphorylation was detected in both inhibitory and excitatory mGlu5-expressing cells, suggesting that type I mGlus have a complex role in nociceptive processing.
6
Suthamnatpong, Ornsiri. "Organisational aspects of the superficial dorsal horn of the lumbar spinal cord". Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263765.
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Nagy, Gergely György. "Glutamate receptors in the spinal cord with emphasis on the dorsal horn". Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/30731/.
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Glutamate is the principal excitatory neurotransmitter throughout the CNS, including the spinal cord. It acts on ionotropic (iGluR) and metabotropic glutamate receptors. Three iGluR families have been identified by the development of more-or-less selective agonists: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors. Both AMPA (GluR1-4) and NMDA (NR1, NR2A-D) receptors have been detected in the spinal cord and these play a major role in physiological processes such as fast excitatory transmission, synaptic plasticity and neuronal development. In addition, they have also been implicated in pathological conditions including neuropathic pain and neurodegenerative disorders. However, very little is known about the synaptic distribution of these receptors in the spinal gray matter. This is because conventional immunocytochemical techniques, generally used to investigate the location of proteins in the CNS, fail to detect these subunits at synapses due to the presence of an elaborate protein meshwork associated with the postsynaptic membrane, which masks synaptic receptors. Postembedding immunocytochemistry on freeze-substituted, Lowicryl-embedded material is a technique which has been used exclusively for the detection of synaptic AMPA and NMDA receptors. This project initially set out to use this method to examine these receptors on neurons of the adult rat spinal cord, with emphasis on their involvement in the sensory processing of the dorsal horn. With antibodies against the GluR1, GluR2/3, NR1, NR2A and NR2B subunits, heavy labelling was observed at many asymmetrical synapses and where the plane of section was perpendicular to the cleft, most of the immunogold particles were associated with the postsynaptic density. To examine the receptor expression pattern of selected cell populations a new method was developed which involved the combination of postembedding electron microscopy with immunofluorescence and confocal microscopy. However, during the course of this study heavy immunogold labelling of dense-cored vesicles (dcvs) inside axonal boutons was observed with all NMDA antibodies. Several studies have found iGluRs in primary afferent terminals in the spinal gray matter and these are thought to function as presynaptic receptor, in order to determine whether gold particles found over dcvs corresponded to presynaptic receptors in transit, immunogold reactions were carried out on transgenic mice which lacked the NR2A subunit. Surprisingly, not only did the dev labelling remain in these knock-out animals, but there was also a significant synaptic labelling. This suggested that the postembedding immunogold labelling observed with the NR2A antibody was non-specific. Since the labelling patterns were similar with other NMDA antibodies this cast doubts on the validity of the postembedding method for detecting NMDA receptors.
8
Heppenstall, Paul Alexander. "Mechanisms of neurokinin₁ receptor action in the dorsal horn of the spinal cord". Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/29799.
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This study addressed the role of neurokin1 (NK1) receptors in nociceptive transmission and their participation in a series of events involving glycine and NMDA receptor-mediated effects on spinal neurons. Using an in vivo electrophysiology protocol utilising ionosphoresis and extracellular recording from laminae III-V dorsal horn neurones of anaesthetised rats, the mechanisms of these interactions were assessed. The functions of the inflammatory cytokine leukaemia inhibitory factor (LIF) were also considered. Injury-induced alterations in the spinal expression pattern of this factor and the consequences of these changes to neuropeptide and excitatory amino acid expression were measured using in situ hybridisation. 1. The involvement of NK1 receptors in spinal pain transmission may be dependent upon the duration and intensity of the nociceptive stimulus. 2. NK1 receptors can contribute to the processing of sustained nociceptive stimuli by modulating excitatory amino acid-mediated transmission, particularly through potentiation of NMDA receptor activity. 3. LIF is a neuroactive cytokine that is associated with peripheral nerve injury. Using in situ hybridisation, the present study has examined the distribution of LIF mRNA in the spinal cord, normally or following peripheral inflammation or nerve injury and determined the consequences of intrathecally applied LIF on spinal expression of NK1 receptor and the high affinity glutamate transporter, EAAT2. In control animals, dorsal horn expression of LIF was high in superficial laminae I-II with only light expression in the deeper laminae III-V and in the ventral horn. Both peripheral inflammation and neuropathy significantly increased levels of LIF mRNA in the dorsal horn and this was most evident in the lateral parts of laminae I and II. Interactions within the spinal cord may underlie the plasticity of the dorsal horn in sensory processing. This has been discussed with reference to the regulation of short-term co-operation between NK1 and NMDA receptors by glycine and to long-term modifications of peptide and excitatory amino acid neurotransmission by altered LIF gene expression.
9
Laird, Jennifer Marie Ann. "Dorsal horn neurones in the sacral spinal cord of the rat : receptive field and encoding properties". Thesis, University of Bristol, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330080.
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Maile, Rebecca Ann. "Sensory processing in the isolated in vitro rat spinal cord with particular emphasis on opioid-related peptides, excitatory and inhibitory amino acids". Thesis, University of Southampton, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249598.
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11
Miyazaki, Yoshiya. "Xenon Has Greater Inhibitory Effects on Spinal Dorsal Horn Neurons than Nitrous Oxide in Spinal Cord Transected Cats". Kyoto University, 2000. http://hdl.handle.net/2433/181269.
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12
Stewart, Anika Louise. "Which neurones in the superficial dorsal horn of the rat spinal cord mediate acute itch?" Thesis, University of Liverpool, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425704.
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Lever, Isobel Jane. "The release of two neuromodulators : BDNF and substance P from the isolated spinal cord dorsal horn". Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407449.
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Rottkamp, Catherine Anne-Marie. "The Role of Hox Cofactors in Vertebrate Spinal Cord Development". Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1194575822.
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Ahmed, Sheikh Maie Idil. "Nociceptin and the ORLâ‚ receptor : analgesic mechanisms and interactions with dorsal horn neurones in rat spinal cord". Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423550.
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Perez, Sanchez Jimena. "Unconventional components of inhibition that contribute to the regulation of sensitization in the spinal cord dorsal horn". Doctoral thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/33255.
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La corne dorsale de la moelle épinière contient une population diversifiée de neurones qui sont responsables de l'intégration et de la transmission de l'information liée à la douleur vers le cerveau. L'excitabilité de ces neurones est largement contrôlée par l'acide γ- aminobutyrique (GABA) et la glycine, les deux principaux neurotransmetteurs inhibiteurs du système nerveux central. L'inhibition synaptique conventionnelle est médiée par des récepteurs GABAA et glycine perméables aux chlorures, situés à l’opposé des terminaux présynaptiques. Cependant, un sous-ensemble différent de ces récepteurs est situé à l'extérieur de la synapse et offre une diversité fonctionnelle supplémentaire d'inhibition. Les études présentées dans cette thèse ont utilisé une grande variété d'approches pour explorer deux composantes non conventionnelles de l'inhibition dans la régulation de la transmission liée à la douleur dans la corne dorsale de la moelle épinière. Le premier est le rôle des récepteurs GABAergiques non synaptiques qui produisent une inhibition tonique; le seconde est la régulation des gradients de chlorure intracellulaire qui déterminent la force de l'inhibition GABAergique. Les résultats montrent qu'il existe un gradient d'inhibition à travers la corne dorsale, avec une inhibition plus faible dans les niveaux superficiels, et de plus en plus forte en profondeur. Ceci est démontré par une contribution différentielle des récepteurs GABAA contenant des sous-unités α5 (α5GABAAR) à l'inhibition tonique à travers la corne dorsale de la moelle épinière. L'activité basale de ces récepteurs n'est pas assez forte pour contraindre la sensibilisation à l'information liée à la douleur, mais contribue à la récupération de ces états sensibilisés. Le renforcement de l'activité de αGABAARs ne limite pas non plus la sensibilisation. En revanche, l'activité d'autres récepteurs GABAA producteurs d'inhibition tonique, à savoir ceux contenant des sous-unités δ (δGABAAR), peut être améliorée pour diminuer la sensibilisation dans la corne dorsale. D'autre part, il y a aussi un gradient dans l'homéostasie du chlorure, qui affecte la façon dont les différents neurones intègrent les entrées synaptiques. En fait, j'ai decouvert que l'homéostasie du chlorure module la propension et la stabilité de la plasticité synaptique. Une activité plus élevée de l'extrudeur neuronal du chlorure (KCC2), telle que celle présente dans les niveaux plus profonds de la corne dorsale, est directement liée à une reduction de la potensialisation a long-terme (LTP). Inversement, une faible capacité d'extrusion de chlorure dans les niveaux superficiels conduit à une LTP accentué dans la corne dorsale. En conclusion, j'ai découvert un gradient d'inhibition à travers la corne dorsale qui détermine la sensibilisation de l'information nociceptive. Une inhibition faible aux niveaux superficiels conduit à une plasticité synaptique améliorée et sans contrainte, alors qu'une inhibition plus forte contraint la plasticité aux niveaux plus profonds de la corne dorsale.The dorsal horn of the spinal cord contains a diverse population of neurons that are responsible for the integration and transmission of pain-related information into the brain. The excitability of these neurons is largely controlled by γ-aminobutyric acid (GABA) and glycine, the two main inhibitory neurotransmitters in the central nervous system. Conventional synaptic inhibition is mediated by chloride-permeable GABAA and glycine receptors, located directly opposite to presynaptic terminals. However, a different subset of these receptors is located outside the synapse and provides further functional diversity of inhibition. The studies presented in this thesis employed a wide variety of approaches to explore two non-conventional components of inhibition in the regulation of pain-related transmission in the dorsal horn of the spinal cord. The first is the role of non-synaptic GABAergic receptors that produce tonic inhibition; the second is the regulation of intracellular chloride gradients that determine the strength of GABAergic inhibition. The results show that there is a gradient of inhibition across the dorsal horn, with weaker inhibition in superficial levels, and increasingly stronger in deeper levels. This is evidenced by a differential contribution of α5 subunit-containing GABAA receptors (α5GABAARs) to tonic inhibition across the dorsal horn of the spinal cord. Importantly, the basal activity of these receptors is not strong enough to counter sensitization of pain-related information but contributes to the recovery from these sensitized states. Enhancing the activity of α5GABAARs also does not constrain sensitization. In contrast, the activity of other tonicinhibition- producing GABAA receptors, namely those that contain δ subunits (δGABAARs), can be enhanced to decrease sensitization in the dorsal horn. On the other hand, there is a also gradient in chloride homeostasis, which affects how different neurons integrate synaptic inputs. In fact, I found that chloride homeostasis modulates the propensity and stability of synaptic plasticity. As such, higher activity of the neuronal chloride extruder (KCC2), such as that present in deeper levels of the dorsal horn, is directly linked to a stable, or constrained, long-term potentiation (LTP). Conversely, low chloride extrusion capacity in superficial levels leads to enhanced and unstable LTP in the dorsal horn. In conclusion, I uncovered a gradient of inhibition across the dorsal horn that shapes the sensitization of nociceptive information. Weak inhibition at superficial levels leads to enhanced and unconstrained synaptic plasticity, whereas stronger inhibition stabilizes plasticity at deeper levels of the dorsal horn
17
De, Koninck Yves. "Physiology, chemistry and immunocytochemistry of selected synaptically elicited responses in dorsal horn neurones aof the cat spinal cord". Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=70211.
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The studies presented in this thesis relate to the physiological, chemical and immunocytochemical characterization of specific synaptically elicited responses following activation of defined sensory inputs to dorsal horn neurones in the spinal cord of the cat.Low-threshold mechanical stimulation of the skin produced two types of inhibitory postsynaptic potential (IPSP) in dorsal horn neurones. One was shown to involve $ gamma$-aminobutyric acid (GABA) acting on a GABA$ sb{ rm A}$ receptor and the other one involves adenosine acting on a P$ sb1$-purinergic receptor. The adenosine-mediated IPSP is mediated by activation of ATP-sensitive K$ sp+$ channels. Further characterization of these IPSPs revealed that the adenosine-mediated IPSP is involved in a system responding optimally to repetitive mechanical stimulation.
Stimulation of hair afferents produced EPSPs which are mediated by an excitatory amino acid. Characterization of the input from single hair afferents to single dorsal horn neurones revealed that the central excitatory response to guard-hair afferent input, but not that to down-hair afferent input is subject to a prolonged GABA$ sb{ rm A}$-mediated inhibitory mechanism.
The response to noxious cutaneous stimulation involves at least two types of EPSP in dorsal horn neurones. The fast EPSP in response to a brief stimulus is probably elicited by an excitatory amino acid, whereas sustained noxious stimulation elicits a slow, prolonged EPSP mediated by substance P acting on the NK-1 receptor.
These results demonstrate the participation of specific chemical mechanisms in the mediation of specific physiological responses in identifiable sensory pathways in the spinal cord.
18
Maie, I. A. S. "Nociceptin and the ORL-1 receptor : analgesic mechanisms and interactions with dorsal horn neurones in rat spinal cord". Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444486/.
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There is a need to improve our understanding of the mechanisms of pain, especially neuropathic pain in order to develop new analgesic drugs based on opioids. In recent years, the cloning of the novel opioid receptor like-1 (ORLi/NOP) receptor and studies on the effectiveness of opioids in pain models provides a basis for potential novel therapy. This thesis is based on nociceptin/orphanin FQ and its receptor ORLi, which represent a novel peptide/receptor system pharmacologically different from classical opioid systems. Nociceptin regulates several biological functions, both at the peripheral and central levels therefore, the ORLi receptor may be viewed as a novel target for drug development. However, the pharmacology of this receptor is still under study, with few molecules selectively acting on this receptor. Little is known about the physiological roles of this new opioid system. Using an in vivo electrophysiology study, spinal effects of nociceptin were investigated on deep dorsal horn neurones in normal, sham operated and neuropathic rats. Nociceptin induced a greater dose-dependent inhibition in normal animals when compared with the neuropathic and sham operated animals which were the least inhibited. Additionally to clarify the role of nociceptin and its receptor in the spinal processing of pain a non peptide antagonist and agonist of nociceptin were studied. Another objective of this thesis was to study the interaction between nociceptin and cholecystokinin (CCK), an anti-opioid peptide. CCK enhanced the inhibitory effect of nociceptin in sham operated and neuropathic animals, whereas in normal animals CCK had the expected antiopioid action. Furthermore, this thesis emphasizes the importance of opioid receptors located on lamina I expressing NK1 receptors in the modulation of spinal analgesia of nociceptin when compared to D-Pen2, D-Pen5 enkephalin (DPDPE), a delta-opioid agonist. Finally, this thesis suggests a potential therapeutic value of oxytocin in the treatment of neuropathic pain.
19
Dolique, Tiphaine. "Déséquilibre excitation/inhibition dans la moelle épinière dorsale en situation de douleurs chroniques : rôle des molécules d’adhérence neuroligines". Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21820/document.
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En état de douleur chronique, la sensibilisation centrale s’accompagne d’une modification de l’équilibre excitation/inhibition en faveur d’une excitation accrue de la corne dorsale de la moelle épinière. Cet équilibre implique des molécules d’adhérence telles que les neuroligines postsynaptiques (NLs). Dans une première partie de notre travail de thèse, nous avons étudié la régulation éventuelle de ces protéines dans un modèle de douleur neuropathique (Spinal Nerve Ligation, SNL) chez le rat. Nos données ont montré une surexpression inattendue de la NL2, généralement associée à l’inhibition, alors que l’expression de la NL1, généralement associée à l’excitation, ne change pas. Le blocage de l’expression de NL2 in vivo par application intrathécale de siRNA, a produit des effets anti-nociceptifs réversant de façon significative l’allodynie mécanique observée chez les rats SNL. L’étude ultérieure des partenaires pré- et postsynaptiques de NL2, a démontré une co-variation spécifique avec PSD95, une protéine d’échafaudage des synapses excitatrices. De plus, une approche par co-immunoprécipitation a mis en évidence une augmentation significative des interactions protéiques NL2 /PSD95 chez les rats SNL. Enfin, cette association inhabituelle en condition neuropathique, est apparue liée à la surexpression spécifique de NL2(-), un variant d’épissage de NL2 normalement minoritaire en condition physiologique. La surexpression, l’augmentation d’association avec PSD95, et l’effet pro-nociceptif inattendu de la NL2 « inhibitrice » en condition de douleur neuropathique, indiquent une permutation fonctionnelle de la NL2 de l’inhibition vers l’excitation modifiant le rapport synaptique en faveur d’une excitation globale plus élevée dans la corne dorsale.Dans une deuxième partie du travail, nous avons exploré le rôle des molécules d’adhérence NLs dans la sensibilisation spinale associée à un autre type de douleur chronique, à savoir la douleur cancéreuse, sur un modèle de cancer de l’os chez le rat. L’étude de l’expression des NLs et de leurs partenaires, a montré une augmentation d’expression spécifique de la NL1 et de S-SCAM, une autre protéine d’échafaudage des synapses excitatrices. D’autre part, d’après la littérature, ce modèle se caractérise par une importante activation gliale dans les cornes dorsales de la moelle épinière, se traduisant notamment par une astrogliose massive. Cependant, nous avons montré que dans le modèle utilisé, il n’y avait aucune variation ni de marqueurs classiques de l’activation astrocytaire (GFAP, S100β), ni des marqueurs microgliaux (OX-42 et Iba1). Au contraire, tous ces paramètres étaient effectivement augmentés dans la corne dorsale ipsilatérale d’animaux neuropathiques. Ces résultats suggèrent que, contrairement à ce qui a été décrit précédemment, la douleur cancéreuse d’origine osseuse n’est pas nécessairement corrélée à une surexpression spinale des marqueurs de la glie réactive, tandis que la douleur neuropathique l’est.En conclusion, nos résultats obtenus dans le modèle de douleur cancéreuse montrent un phénotype concernant des molécules impliquées dans la formation, la spécification et la modulation des synapses, bien différent de celui que nous avons mis en évidence dans le modèle de douleur neuropathique. Nous montrons notamment dans les deux modèles, une implication bien distincte des molécules d’adhérence NLs et de la glie confortant les données de la littérature indiquant que ces deux grandes catégories de douleur chronique ont chacune une signature propre. De plus, nos résultats ouvrent la perspective d’identifier de nouveaux diagnostics et/ou de nouvelles possibilités thérapeutiques, en ciblant spécifiquement les NLsIn chronic pain states, central sensitization is associated with a modification in the excitation/inhibition balance toward increased excitation in the spinal dorsal horn. This balance involves adhesion molecules such as the postsynaptic Neuroligins (NLs). In a first part of our thesis work, we investigated the putative regulation of these proteins in the Spinal Nerve Ligation (SNL) model of neuropathy in the rat. Our data showed an unexpected upregulation of NL2, usually associated to inhibition, whereas expression of NL1, usually associated to excitation, did not change. The in vivo expression blockade of NL2 by intrathecal injection of siRNAs, produced specific antinociceptive effects, significantly reversing the SNL-induced mechanical allodynia. Subsequent study of pre- and postsynaptic NL2 partners, demonstrated a specific co-variation with PSD95, a scaffolding protein of excitatory synapses. Moreover, a co-immunoprecipitation approach showed a significant increase of NL2/PSD95 protein interactions in SNL rats. Finally, this unusual association in neuropathic conditions, appeared to be linked to specific over-expression of NL2(-), a NL2 splice variant usually a minority in physiological conditions. Over-expression, increased association with PSD95, and unexpected pronociceptive effect of the “inhibitory” NL2 in neuropathic pain condition, suggest a functional shift of NL2 from inhibition to excitation changing the synaptic ratio toward higher overall excitation in the dorsal horn.In a second part of our work, we investigated the role of the NLs adhesion molecules in spinal sensitization associated with another type of chronic pain, namely cancer pain, using a rat model of bone cancer. The study of the expression of NLs and partners, showed a specific increase in the expression of NL1 and S-SCAM, another postsynaptic scaffolding protein at excitatory synapses. Moreover, according to the literature, this model is characterized by a strong glial activation in the spinal dorsal horn, identified especially by a massive astrogliosis. However, we showed that in the bone cancer model used, there was no variation, neither in the classical markers of astrocyte activation (GFAP, S100β), nor in microglial markers (OX-42 et Iba1). On the contrary, all these parameters did actually increase in the ipsilateral dorsal horn of SNL neuropathic rats. These results suggest that, at odd with what was previously described, bone cancer pain is not necessarily correlated with a spinal overexpression of markers of reactive glia, whereas neuropathic pain is.In conclusion, our results obtained with the cancer pain model, show that the molecules involved in the formation, specification and modulation of synapses, yield a phenotypes clearly different to the one evidenced in the model of neuropathic pain. More particularly, we show in the two models, a well distinct involvement of the NL adhesion molecules and of glia, reinforcing reports from the literature, which indicate that the two important categories of chronic pain, cancer and neuropathic, each have a peculiar signature. Moreover, our results raise the possibility that new diagnosis and/or new therapeutic possibilities may emerge from targeting NL expression
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Pitcher, Mark H. "The effects of persistent peripheral inflammation on the ultrastructural localization of spinal cord dorsal horn group I metabotropic glutamate receptors /". Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98770.
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Persistent peripheral inflammation is thought to induce functional plasticity of spinal dorsal horn neurons, and may produce changes in glutamate receptor expression. Alterations in expression and cellular localization of group I metabotropic glutamate receptors (mGluR1alpha and mGIuR5) is important in various neuronal systems, and these receptors are also known to modulate nociceptive neurotransmission in the spinal dorsal horn. The aim of the present study is to determine whether persistent inflammation produces alterations in ultrastructural localization of mGluR1alpha and mGluR5 in the dorsal horn of the spinal cord. Persistent inflammation was induced in rats by an intraplantar hindpaw injection of complete Freund's adjuvant (CFA). Three days after the CFA injection, rats were perfused with fixatives, and spinal cords were removed and the lumbar segments L3-L5 were sectioned using a vibratome. Using pre-embedding immunocytochemical protocols for electron microscopy, we quantified immunogold-labeled mGluR1alpha and mGluR5, in lamina IV-V and I-II, respectively, in the spinal dorsal horn of both CFA-treated rats and untreated control rats. Compared to untreated rats, CFA-treated rats had a significant increase in membrane-associated mGluR5 immunogold-labeled particles in lamina I-II neurons. No change in the ratio of membrane vs. intracellular mGluR1alpha receptors was found in CFA-treated rats, however membrane-bound mGluR1alpha moved closer to the synapse in CFA-treated as compared with untreated rats. These findings suggest that persistent peripheral inflammation elicits increased availability of spinal dorsal horn group I mGluR's for synaptically-released glutamate binding. Thus, trafficking of Group I mGluR's may underlie the development of plastic changes in spinal dorsal horn neurons and associated persistent inflammation-induced chronic pain.
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Wood, Malcolm S. "Characterization of opioid binding sites in spinal cord and other tissues". Thesis, Loughborough University, 1988. https://dspace.lboro.ac.uk/2134/25215.
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The binding of [³H]opioid ligands to homogenates prepared from the spinal cords of rat and other species has been studied. Similar numbers of sites were seen in all areas of the cord when measured in a rostrocaudal direction. There was found to be approximately 2 x higher density of sites in the dorsal half of the cord compared with the ventral half. Binding studies suggested a similar relative distribution of mu, delta and kappa sites in all areas of the cord. The results are discussed in relation to the reported distribution of opioid peptides. In the above study the kappa binding site was defined as the binding of [³H] unselective opioids in the presence of cold ligands to suppress binding to mu- and delta-sites. Competitive binding assays, however, suggested this site did not have the properties of a single homogeneous group. Approximately 50% of the apparent kappa binding was consistent with a classical kappa site. Saturated binding assays afforded Bmax values which suggested lower 'true' kappa site numbers than previously supposed, values which were confirmed using the kappa peptide' [³H]Dynorphin A-(1-9), and the kappa selective [³H]U-69593. Heterogeneity was also seen in other central nervous system tissues. The heterogeneous nature of the kappa site may be due to different sites, due to interactions at a non-opioid site or may represent different conformations of the same site. The second possibility was discounted since observed binding followed the cellular distribution of the plasma marker Na+/K+-ATPase was stereoselective for levorphanol over dextrorphan, and fully displaceable by naloxone. The third possibility was investigated by studying the role of Na+ and MG2+ ions, which are reported to affect receptor conformation in binding assays employing brain tissues. None of the results obtained suggested that conformational changes were responsible for the observed effects, although the experiments were not exhaustive.
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Ben, Ayed Sara [Verfasser], e Hilmar [Akademischer Betreuer] Bading. "Ca2+ signalling and its consequences in the mouse spinal cord dorsal horn under chronic pain / Sara Ben Ayed ; Betreuer: Hilmar Bading". Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/1197056777/34.
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Merighi, Adalberto. "Light and electron microscopical studies on the distribution of peptides and 'classical' neurotransmitters in dorsal root ganglion cells and in the dorsal horn of the spinal cord". Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46446.
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Bailey, Andrea Lee. "A behavioural and morphological analysis of compromised primary afferent C-fibre input to the superficial dorsal horn of the rat spinal cord". Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66754.
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Neuropathic pain is caused by direct or indirect damage of the central nervous system or of primary afferent fibres (PAF). Small diameter C-fibres (C-PAF) are of great interest as they are responsible for the transduction of pain-related signals arising from the periphery. The adult C-fibre neuronal populations can be distinguished by their neuropeptide expression profile. The peptidergic population expresses neuropeptides such as substance P (sP) and calcitonin gene-related peptide (CGRP). The non-peptidergic C-fibres express the cell surface glycoproteins binding the plant lectin IB4 and lack neuropeptides. Non-peptidergic afferents are known to play a role in nociceptive transmission; however our understanding of the nature of this information and how it is processed by these afferents in the spinal cord is limited. In this thesis, we focused on examining the morphological, neurochemical and behavioural consequences of compromised C-PAF input to the superficial dorsal horn. Our approach was two-fold: a) to study the effects of a constriction injury of the sciatic nerve; b to study the effects of selectively ablating the IB4-binding sub-population of C-PAFs by means of an intra-sciatic injection of IB4-Saporin. In the peripheral nerve lesion study we examined the time-related effects of a constriction neuropathy on the peptidergic and non-peptidergic C-PAFs using neurochemical markers for each neuronal population. We observed a transient loss of IB4-binding in lamina II, resultant from the degeneration of CIa synaptic glomeruli. Paw withdrawal latencies to noxious heat stimuli were significantly reduced in neuropathic animals throughout the 3 week time course. Sensitivity to cold stimuli was also significantly altered in neuropathic animals. Paw withdrawal thresholds to innocuous and noxious mechanical stimulation were significantly reduced in neuropathic animals. We did not detect any change in the deLa douleur neuropathique est causée par des lésions des fibres afférentes primaires. Les fibres nerveuses de type C (non-myélinisées) sont d'un intérêt particulier, étant responsables de la transmission des influx douloureux provenant de la périphérie. La population de fibres nerveuses C est hétérogène: a) la population peptidergique contient des neuropeptides comme la substance P (sP) et le peptide lié au gène de la calcitonine (CGRP); b) la population non-peptidergique a la capacité de se lier à la lectine IB4. Notre compréhension de la nature de l'information nociceptive et des mécanismes impliqués dans le traitement de celle-ci par ces fibres afférentes non-peptidergiques dans la moelle épinière restent limités. Dans cette thèse, nous avons étudié les conséquences morphologiques, neurochimiques et comportementales des lésions des fibres afférentes primaires de type C (C-PAFs) dans la corne dorsale superficielle. Cet effort fut mené de deux façons: soit par des lésions produites par constriction du nerf sciatique, soit par suppression sélective de la sous-population de C-PAFs se liant à IB4. L'observation des terminaisons des PAFs se liant à IB4 dans la couche II révélait la perte passagère du marquage d'IB4 résultant de la dégénérescence des glomérules synaptiques CIa. Des tests mesurant les temps de retrait de patte en réponse à des stimulations mécaniques, thermiques chaudes et froides appliquées à la périphérie furent effectués chez ces animaux. Spécifiquement, les seuils de retrait étaient plus faibles lors des tests de nociception thermique effectués au cours des trois semaines d'étude. La réactivité aux stimulations froides était également significativement altérée chez les animaux neuropathiques. Les seuils de retraits de patte vis-à-vis les stimulations mécaniques étaient significativement réduits chez les animaux neuropathique
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Plenderleith, M. B. "The effects of neonatal capsaicin treatment on the functional properties of sensory neurones in the dorsal horn of the rat spinal cord". Thesis, University of Bristol, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356742.
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Dhanasobhon, Dhanasak. "Spinal cholinergic system and chronic pain". Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ090/document.
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Chez les rongeurs et humains, un « tonus » cholinergique spinal endogène modulant les comportements nociceptifs (douloureux) a été décrit. Une source potentielle de cette acétylcholine sont les interneurones cholinergiques de la corne dorsale (CD) de la moelle épinière. Nos objectifs étaient les suivants : (1) caractériser le « tonus » cholinergique spinal responsable de l’établissement des seuils mécaniques nociceptifs et (2) élucider le rôle des neurones cholinergiques CD dans la modulation de l'information sensorielle chez des animaux naïfs et neuropathiques. Nous avons confirmé la présence d'un « tonus » cholinergique qui module les seuils mécaniques et démontré qu'il est encore présent, bien qu'il soit modifié, après une neuropathie. Les interneurones cholinergiques reçoivent des entrées excitatrices localisées sur des segments plus distants et reçoivent généralement une faible fréquence d’entrées inhibitrices. De plus, ils sont indirectement reliés par des afférences primaires nociceptives qui expriment TRPV1, ce qui démontre leur implication dans le circuit nociceptif. Dans les conditions neuropathiques, les entrées des neurones LIII / IV ne sont pas affectées après une lésion du nerf périphérique. Une meilleure compréhension du système cholinergique spinal peut ouvrir la voie à une thérapie alternative contre la douleurAn endogenous spinal cholinergic tone modulating nociceptive (painlike) behaviors has been demonstrated in rodents and humans. One potential source of this acetylcholine is the spinal Dorsal Horn (DH) cholinergic interneurons. Our objectives were to: (1) characterize the spinal cholinergic tone establishing mechanical nociceptive thresholds and (2) to elucidate the role of DH cholinergic neurons in the modulation of sensory information of naïve and neuropathic animals. We have confirmed the presence of a cholinergic tone modulating mechanical thresholds and demonstrated that it is still present, although altered, after neuropathy. The DH cholinergic interneurons receive excitatory inputs from distant spinal segments and generally receive lower inhibitory inputs. In addition, they are indirectly connected by a subset of nociceptive primary afferents expressing TRPV1, demonstrating their involvement in nociceptive processing. In neuropathic spinal circuits, the inputs to LIII/IV neurons appears to be unaffected after injury. Better understanding the spinal cholinergic system can pave way to alternative pain therapy
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Morgan, Elise. "The in vitro rat spinal cord : an investigation into the role of excitatory glutamate in nociception using electrophysiological and immunohistochemical techniques". Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313208.
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Ford, Neil C. "The role of voltage-independent cation channels in shaping spinal nociceptive circuit output and pain sensitivity in developing rodents". University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1530798481340688.
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Seibt, Frederik. "Effets de la noradrénaline sur les transmissions synaptiques dans la corne dorsale de la moelle épinière de rat". Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ029/document.
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La corne dorsale de la moelle épinière (CDME) est un site d’intégration et de modulation de l’information somatosensorielle. Les laminae profondes de la CDME jouent un rôle important dans la modulation des informations nociceptives. Notre objectif a été de caractériser les effets de la NA sur la transmission synaptique des laminae profondes de la CDME. Nous montrons que la NA facilite la transmission synaptique inhibitrice dans les laminae III-V de la CDME. Ce phénomène met en jeu l’activation d’adrénocepteurs alpha1, alpha2, et bêta et nécessite une communication interlaminaire intacte entre les laminae III-IV et V. L’inhibition du métabolisme glial produit les mêmes effets qu’une section mécanique entre les laminae IV et V. Une interaction entre les cellules gliales et les neurones des laminae profondes la CDME semble donc indispensable à l’effet facilitateur de la NAThe dorsal horn of the spinal cord (DH) is an important site of integration and modulation of somatosensory information and deep laminae of the DH play an important role in the modulation of nociceptive information in the neuronal network of the spinal cord.Our aim was to characterize the effects of NA on synaptic transmission in deep laminae of the DH.We show that NA facilitates inhibitory synaptic transmission in laminae III-IV of the DH. This phenomenon involves the activation of alpha1, alpha2, and beta adrenoceptors and requires intact interlaminar communications between laminae III-IV and V. Glial cell metabolism inhibition has the same consequences as a mechanical section between laminae IV and V. These results indicate that an interaction between glial cell and deep laminae neurons of the DH seems essential for the facilitatory effect of NA on inhibitory synaptic communications in laminae III-IV of the DH
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Gerke, Michelle Barbara. "Characterisation of the expression of cell-surface carbohydrates by primary sensory neurones and their applications in the study of pain". Thesis, Queensland University of Technology, 2000.
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Mesnage, Bruce. "Système cholinergique et modulation de la transmission nociceptive spinale". Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ122/document.
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L’acétylcholine (ACh) endogène de la corne dorsale de la moelle épinière (CDME) exerce une analgésie puissante utilisée en clinique, dont la source et les mécanismes demeurent inconnus. Elle siège probablement au niveau d’un plexus de fibres cholinergiques de la CDME d’origine non-élucidée. Dans ce contexte, nous avons pu établir que ce plexus est principalement issu d’interneurones cholinergiques spinaux caractérisés dans ces travaux, qui seraient donc le substrat probable de l’analgésie décrite. Décrits comme concourant aux effets aigus et analgésiques de la morphine, nous avons, par ailleurs, pu observer que les récepteurs de l’ACh participaient également aux effets chroniques et pro-algésique de la morphine, notamment au niveau de la CDME. Ceci place donc l’ACh comme un effecteur ou intermédiaire de la morphine.Nos travaux suggèrent ainsi que le système cholinergique spinal pourrait constituer une cible thérapeutique alternative pour de nouveaux traitements de la douleurIn the spinal cord dorsal horn (SCDH), endogenous acetylcholine (ACh) acts as a powerful analgesia, of clinical use. Though its source and mechanisms remain unravelled, this analgesia probably lies in a plexus of cholinergic fibers (PCF) located in the SCDH and of undetermined origin. In this context, we established that the PCF mainly originates from a spinal population of cholinergic interneurons, fully characterized in this work. These are, thus, the likely substrate of the spinal cholinergic analgesia.Besides, ACh receptors (AChR) partly mediate the analgesic acute effects of morphine. In this work, we also observed that a chronically-administered AChR agonist reproduces as well the pro-algesic effects of morphine in the same conditions. Thus, ACh appears as a possible intermediary or a final effecter of the morphine pain pathways.Our data suggest that the cholinergic system could become a new putative therapeutic target in pain management and treatment
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Zell, Vivien. "Impact des glucocorticoïdes circulants sur la maturation et le fonctionnement de l'inhibition spinale GABAergique". Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ097/document.
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Les glucocorticoïdes (GC) sont des hormones stéroïdes synthétisées par les glandes surrénales. La production de ces GC est une des réponses de l’organisme pour rétablir l’homéostasie grâce à différentes actions comprenant des effets centraux sur le comportement et la douleur. C’est ce dernier qui a fait l’objet de mes travaux dans le cadre de cette thèse.Les afférences sensorielles primaires véhiculent les informations de la périphérie dans les cornes dorsales de la moelle épinière. Ces informations qui peuvent être nociceptives sont modulées par un réseau de neurones spinal avant d’être transmises et intégrées. Nous avons montré que les GC sont impliqués dans la maturation et le fonctionnement de la transmission inhibitrice faisant intervenir le neurotransmetteur GABA. Dans les cornes dorsales, cette inhibition est cruciale pour limiter les mécanismes de transmission de l’information nociceptiveGlucocorticoids (GC) are steroid hormones synthesized in adrenals following HPA axis activation. GC production is a response of the organism to alleviate homeostasis perturbations through different actions. One of them involves central neuronal modulation of behavior and pain perception.Primary afferents convey peripheral sensory information in the dorsal horns of the spinal cord. This information can be nociceptive and are modulated by a spinal neuronal network before being transmitted and integrated. We showed that GC are implied in the maturation and functioning of the inhibitory transmission involving GABA neurotransmitter. In the dorsal horns this inhibitory transmission is of major importance, limiting the processing of nociceptive information
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Kuster, Robin. "Modulation sexe-dépendante du traitement des informations nociceptives par l'inhibition GABAergique spinale". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ016.
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La plasticité à court-terme des synapses GABAergiques dans la lamina II de la moelle épinière est essentielle pour le traitement des messages nociceptifs. Cette plasticité diffère selon le type de neurone postsynaptique, excitateur ou inhibiteur. Nos résultats indiquent une modulation liée au sexe de la transmission synaptique GABAergique, et donc une modification de la plasticité des synapses GABAergiques, notamment en réponse à une inflammation périphérique aiguë. Ces modulations soulignent l'importance de la balance entre l’inhibition et l’excitation dans le traitement des informations nociceptives. Ces observations suggèrent que les mécanismes de modulation de la transmission synaptique GABAergique pourraient expliquer les disparités de sensibilité mécanique et thermique au chaud selon le sexe. Nos travaux enrichissement la compréhension des mécanismes neurobiologiques de la nociception, en tenant compte des différences liées au sexe encore trop souvent négligéesThe short-term plasticity of GABAergic synapses in the lamina II of the spinal cord is essential for processing nociceptive information. This plasticity varies depending on the type of postsynaptic neuron, whether excitatory or inhibitory. Our findings indicate a sex-specific modulation of GABAergic synaptic transmission, particularly in response to acute peripheral inflammation. These observations highlight the importance of maintaining a balance between inhibition and excitation in processing nociceptive information. They also suggest that mechanisms regulating GABAergic synaptic transmission may explain differences in mechanical and thermal sensitivity between males and females.Our work enhances understanding of the neurobiological mechanisms of nociception, considering often overlooked sex-related differences
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Saeed, Abeer Wael. "Chronic neuropathic pain and spinal dorsal horn plasticity". Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110356.
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Chronic pain is a debilitating disease with a very important socio-economic burden. The objective of this thesis was to contribute to our understanding of the normal organization of the dorsal horn of the spinal cord and its changes in chronic neuropathic pain, a form of chronic pain that sometimes follows lesions of the nervous system. Our studies focused on two important components of spinal cord pain-related circuitry, the projection neurons and their innervation by the small diameter nociceptive afferents. Spinal lamina I projection neurons have been classified, based on their morphology into fusiform, multipolar and pyramidal neurons. The two former types have been shown to respond to noxious stimuli and express the substance P receptor (NK-1r), while pyramidal neurons seldom express the NK-1r and respond to innocuous cooling only. The two main populations of small diameter nociceptive afferents are the peptidergic, which expresses the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the non-peptidergic, which is mostly devoid of neuropeptides but binds the plan lectin IB4. In the first experimental chapter, we investigated the changes that occur at the level of the spinal dorsal horn in an animal model of chronic neuropathic pain. We demonstrated a de novo expression of NK-1r by pyramidal neurons, similar to that previously observed in our laboratory in a chronic arthritis model. This phenotypic switch was associated with a dramatic increase in the peptidergic (SP-immunoreactive) innervation of this cell population, which normally is sparsely innervated by these fibers. To assess whether pyramidal neurons responded to noxious stimuli in neuropathic animals, we injected capsaicin in the hind paw, which induced a massive internalization of NK-1r on these neurons, an indication of cell activation. To assess whether a chronic pain state was needed to trigger the expression of NK-1r by pyramidal neurons, in the second experimental chapter of this thesis we used a model in which there is no chronic pain but in which previous work from our laboratory had revealed a marked increase in NK-1r in the dorsal horn. In this model, the non-peptidergic population of nociceptive afferents is specifically ablated by the injection of the neurotoxin saporin conjugated to the lectin IB4 (IB4-SAP) into the sciatic nerve. The animals did not display any pain-related behavioral changes. However, we observed a significant upregulation of NK-1r in lamina I, in neuronal types that normally expressed it (i.e. fusiform and multipolar cells), with no de novo expression by pyramidal neurons. In the third experimental chapter, we addressed the issue of whether lamina I projection neurons which express the NK-1r are innervated by non-peptidergic nociceptive afferents, as a study in a transgenic mouse model had provided data suggesting that non-peptidergic afferents had connections with deep dorsal horn neurons but not with lamina I NK-1r-expressing cells. We performed a systematic study aimed at identifying the normal connections of the non-peptidergic nociceptive fibers with lamina I neurons using both confocal and electron microscopy and we found a considerable innervation by non-peptidergic afferents on all three types of lamina I projection neurons. The results of this thesis, taken together with previous data from our lab, suggest that a chronic pain state, such as neuropathic pain, seems necessary to trigger a de novo expression of NK-1r in pyramidal neurons and their increased innervation by peptidergic afferents. Further studies are required to clarify the role, in normal nociception and chronic pain states, of the significant direct innervation of lamina I projection neurons by non-peptidergic afferents which we revealed for the first time.La douleur chronique est une condition débilitante ayant de sérieuses répercussions socio-économiques. L'objectif de cette thèse était de mieux comprendre l'organisation de la corne dorsale de la moelle épinière et les changements qui s'y produisent dans les cas de douleurs chronique neuropathique suite à une lésion du système nerveux. Nos études se sont concentrées sur deux composantes importantes des circuits de la douleur: les neurones de projection et leur innervation par les afférents nociceptifs de petit diamètre. Les neurones de projection de la couche 1 de la moelle épinière sont classées selon leur morphologie en 3 types: les neurones fusiformes, multipolaires et pyramidaux. Les deux premiers répondent aux stimuli douloureux et expriment le récepteur de la substance P (NK-1r), alors que les neurones pyramidaux n'expriment ce récepteur qu'occasionellent et répondent au froid non-douloureux. Les deux populations d'afférents principales sont les fibres de petit diamètre peptidergiques, qui expriment la substance P et le "calcitonin gene-related peptide" (CGRP), et les non-peptidergiques, qui sont dépourvues de neuropeptides et qui s'associent avec la lectine IB4. Lors du premier chapitre expérimental, nous avons étudié les changement qui se produisent dans la corne dorsale de la moelle épinière dans un modèle de douleur neuropathique chronique. Nous avons démontré une expression de novo du NK-1r sur les neurones pyramidales, un changement similaire à celui se produisant dans un modèle d'arthrite chronique. Ce changement de phénotype était associé à une augmentation significative du nombre d'appositions peptidergiques faites sur cette population neuronale, qui reçoit habituellement très peu de ces entrées. Afin de vérifier si ces récepteurs sont fonctionnels et répondent aux stimuli douloureux, nous avons injecté de la capsaicine dans la patte arrière, ce qui a mené à une internalisation du récepteur, marquant l'activation de celui-ci. Le deuxième chapitre de cette thèse vérifie si un état de douleur chronique est nécéssaire pour ce changement phénotypique, utilisant une lésion non douloureuse qui cause une augmentation signnificative du NK-1r dans la corne dorsale. Dans ce modèle, une population de nocicepteurs non peptidergiques est excise par une injection dans le nerf sciatique de la toxine saporine conjuguée à la lectine IB4 (IB4-SAP). En absence de symptômes douloureux, la couche 1 de la corne dorsale des animaux lésés a subi une augmentation générale du NK-1r mais sa distribution cellulaire est restée normale, sans expression de novo sur les cellules pyramidales.Lors du troisième chapitre de cette thèse, nous avons vérifié si les neurones de projection de la couche 1 exprimant le NK-1r recevaient des entrées des fibres nociceptives non peptidergiques, comme ce sujet était controversé suite à une publication utilisant des souris transgéniques démontrant une absence de connections de la sorte. Nous avons fait une étude systématique utilisant la microscopie confocale et électronique et avons démontré que les 3 types morphologiques de cellules de projection reçoivent des entrées non peptidergiques directes.Pris ensembles, les résultats de cette thèse suggèrent qu'une condition de douleur chronique est nécessaire pour l'expression du NK-1r sur les neurones pyramidaux et l'augmentation des entrées peptidergiques faites sur celles-ci. D'autres études seront nécessaires pour clarifier l'implication des entrées non peptidergiques faites sur les neurones de projection dans la nociception normale et dans la douleur chronique.
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Waters, Alexander Juergen. "Control of spinal nociception by the midbrain periaqueductal grey matter". Thesis, University of Bristol, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310695.
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Ganley, Robert. "Characterisation of distinct inhibitory interneuron populations in the spinal dorsal horn". Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/7003/.
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The dorsal horn of the spinal cord is the first node in the somatosensory pathway, and is an area essential for controlling the flow of sensory information sent to the brain. Interneurons constitute the vast majority of neurons in this area, and between 25-40% of those in laminae I-III are inhibitory. These inhibitory interneurons are critical for normal somatosensation, for example, by suppressing pain in the absence of noxious stimuli. Interneurons of the dorsal horn are poorly understood due to their morphological and functional diversity, and this is a major factor limiting our understanding of the neuronal circuitry of the dorsal horn. In order to better understand sensory processing in the dorsal horn it is first necessary to characterise the neurons in this area, and to determine the neuronal circuits in which they are integrated. To address this issue, two separate and non-overlapping populations of inhibitory interneurons in the dorsal horn were thoroughly characterised in terms of their morphological and physiological properties. To achieve this, whole-cell recordings were taken from neurons labelled with green fluorescent protein (GFP) under the control of the Prion promoter (PrP) and the neuropeptide Y (NPY) promoter in spinal cord slices from mice. The recording electrodes contained Neurobiotin, which filled the cells during recording and was revealed with fluorescent molecules, enabling three-dimensional reconstruction of cell bodies and dendrites and axons of neurons. Slices containing these labelled neurons were then resectioned for immunocytochemical reactions to determine their neurochemical content and their synaptic inputs and outputs. This study demonstrated that both PrP- and NPY-GFP cells were morphologically heterogeneous although neither group contained islet cells, which are a distinct morphological class of interneuron. PrP- and NPY-GFP cells in lamina II could not be distinguished from each other by using hierarchical cluster analysis with measures of somatodendritic morphology. This suggests that morphological properties may not be useful in distinguishing these populations of interneurons. The vast majority of PrP- and NPY-GFP cells either displayed tonic or initial burst firing of action potentials. However, these groups of cells showed significant differences in some of their active and passive membrane properties, such as membrane resistance, spike frequency adaptation and mV drop in action potential height. When hierarchical cluster analysis was used to group these cells in lamina II based on physiological parameters, PrP- and NPY-GFP cells could be distinguished with some accuracy. This suggests that some physiological differences may exist between these two groups. Within the PrP-GFP group there was a subset that included lamina I among its synaptic outputs, and these cells could provide inhibition to the projection neurons located in this lamina, since GFP boutons from this mouse line can form synapses with giant cells and neurokinin-1 receptor (NK1r)-expressing lamina I neurons. Some PrP-GFP cells showed immunoreactivity for neuronal nitric oxide synthase (nNOS) or galanin, and these two groups had slight morphological differences, which included their laminar location and the spread of their processes. Several experimental approaches, such as electrophysiological, pharmacological and anatomical techniques, indicated that PrP-GFP cells received input from many different types of primary afferent fibre, including peptidergic and non-peptidergic C-afferents, as well as low-threshold mechanosensory fibres. Taken together these findings establish the PrP-GFP cells as a much more functionally heterogeneous group than previously reported. NPY-GFP cells were located in laminae II and III, but were preferentially found in lamina III. The lamina III cells had dendrites with a greater dorsoventral extent than the lamina II cells, and this extent was seen be more dorsal from the soma than ventral. Many NPY-GFP cells received synaptic input from C-fibres, and a subset of those tested lacked TRPV1. Since the TRPV1-lacking C-fibres mostly correspond to the non-peptidergic C-fibres, including non-peptidergic nociceptors and C-low threshold mechanoreceptors, this suggests that NPY-GFP cells could receive input from these fibres. Dorsal root stimulation experiments showed that labelled NPY-GFP cells with somata located in lamina III often received synaptic input from unmyelinated C-fibres, and NPY-expressing neurons in lamina III could respond to noxious mechanical stimuli. A select group of NPY-GFP cells were seen to innervate putative anterolateral tract (ALT) neurons located in lamina III, which could be identified by their dense innervation by bundles of axons containing either NPY or calcitonin gene related peptide (CGRP). Taken together these data suggest that the PrP- and NPY-GFP neurons are distinct populations based on their primary afferent input and post-synaptic targets, and that more than one functional population exists within each of these groups. Despite their many differences, morphological parameters do not appear to be useful in distinguishing the PrP- and NPY-GFP cells, or detecting different functional populations within these groups. The PrP-GFP cells are more morphologically heterogeneous than previous reports suggested, and due to similar features with cells that require the transcription factor Bhlhb5 to develop, they may include a population that are involved in suppressing itch-related signals. NPY-GFP cells could play a role in limiting the spread and intensity of noxious stimuli due to their input from C-fibres, and a small subset of these could inhibit ALT neurons in lamina III. These results further support the view that different neurochemical populations of inhibitory neurons have distinct functional roles, and also highlight the complexity of the neuronal circuitry in the superficial dorsal horn.
37
Gormley, Ann Marie. "Transgenic approaches to studying the development of sensory and spinal cord neurons". Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244742.
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38
Greenspon, Charles. "Linear multi-electrode arrays for recording population data from the spinal dorsal horn". Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/52849/.
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The dorsal horn of the spinal cord is a complex laminar structure integrating exteroceptive signals from the primary afferent fibers into the central nervous system. The laminae of the spinal cord exhibit specialised roles and distinct processes occur across the axes of the dorsal horn. One of the most common in vivo approaches to recording spinal activity is single unit electrophysiology of cells that are believed to be representative of the subjects perception of stimuli. This approach has produced invaluable data but has not progressed in over half a century and fails to account for the specialised processes that occur in each lamina as well as the considerable cellular heterogeneity within and between laminae. In this thesis the use of linear multi-electrode array technology with 16 electrodes spaced 50 μm apart to have a total range of 750 μm that allows for simultaneous recordings across the laminae is developed and validated for the spinal dorsal horns of adult Sprague-Dawley rats. To do this a series of experiments were performed. The placement of the electrode was first optimised by creating a somatotopic map of evoked activity following hindpaw stimulation. A comprehensive series of electrical stimuli designed to induce differential primary afferent fiber activity were then given to establish how well the array could interpret fiber evoked activity. Mechanical and thermal stimulus paradigms were examined to evaluate the spatial distribution of responses across the dorsal horn; after optimisation the responses were then examined in the contexts of acute and chronic pain models. We found that the results of the unsorted multi-spike activity across the array correlated extremely well with predicted responses from single-unit studies in the existing literature. Fiber specific activation restricted along the dorso-ventral axis was detected as was the encoding of mechanical and thermal stimuli that were both innocuous and nocuous in nature. Comparisons between local field potentials and spike activity showed that multi-spike activity represented spinal processing of incoming signals significantly better. Induction of pain models strengthened the argument for the use of the technique by showing that it is capable of being used in both longitudinal and multi-treatment group studies. The approach produced vastly more data than the single-unit technique it builds upon with few drawbacks.
39
Kikukawa, Soki. "Regeneration of dorsal column axons after spinal cord injury in young rats". Kyoto University, 1999. http://hdl.handle.net/2433/181700.
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要旨pdfファイル:タイトル「幼若ラットにおける脊髄損傷後の索路の再生」Kyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第7731号
医博第2084号
新制||医||708(附属図書館)
UT51-99-G325
京都大学大学院医学研究科脳統御医科学系専攻
(主査)教授 金子 武嗣, 教授 柴崎 浩, 教授 川口 三郎
学位規則第4条第1項該当
40
Rydh-Rinder, Malin. "Studies on pain-related messengers and receptors in dorsal root ganglia and spinal cord /". Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4553-5/.
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Ogura, Takenori. "Three-dimensional induction of dorsal, intermediate and ventral spinal cord tissues from human pluripotent stem cells". Kyoto University, 2019. http://hdl.handle.net/2433/236613.
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Tyler, Alan Wayne. "Studies on the ionic basis of primary afferent depolarization in the isolated mammalian spinal cord". Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296523.
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Glasgow, Stacey Marie. "The role of PTF1A in spinal cord development". Access to abstract only; dissertation is embargoed until after 5/15/2007, 2006. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=155.
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Araújo, Lucas Guilherme de. "On cholecystokinin-opioid interaction in the spinal dorsal horn following peripheral nerve injury and inflammation /". Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3560-2/.
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Chen, Ying. "Study of the dorsal root reflex activity in an isolated mammalian spinal cord preparation". Thesis, University of Southampton, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359141.
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Manire, Meredith Ann. "Activating Neuron-Intrinsic Growth Pathways to Promote Spinal Cord Regeneration After Dorsal Root Injury". Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/559555.
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Biomedical SciencesPh.D.
Primary sensory axons fail to regenerate into the spinal cord following dorsal root injury leading to permanent sensory deficits. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Current approaches for promoting DR regeneration across the DREZ have had some success, but sustained, long-distance regeneration, particularly of large-diameter myelinated axons, still remains a formidable challenge. Our lab has previously shown that induced expression of constitutively active B-RAF (kaBRAF) enhanced the regenerative competence of injured DRG neurons in adult mice. In this study, I investigated whether robust intraspinal regeneration can be achieved by selective expression of kaBRAF alone or in combination with deletion of the myelin-associated inhibitors or neuron-intrinsic growth suppressors (PTEN or SOCS3). To this end, I used LSL-kaBRAF: brn3a-CreERT2 transgenic mice in which kaBRAF can be induced selectively in sensory neurons. I have also bred LSL-kaBRAF: brn3a-CreERT2 mice with triple knock-out mice lacking Nogo, Mag and OMgp or mouse lines carrying floxed alleles of PTEN or SOCS3. Single, double, and triple conditional mice were subjected to cervical DR crush and AAV2-eGFP vectors were used to selectively label regenerating axons of large-diameter neurons. I compared the extent of regeneration at 3 weeks or 2 months after DR injury using conventional anatomical and behavioral analyses. I found that kaBRAF alone promoted axon regeneration across the DREZ but did not produce significant functional recovery by two months. Supplementary deletion of Nogo, MAG, and OMgp did not improve kaBRAF-induced regeneration. Deletion of PTEN or SOCS3 individually or in combination failed to promote axon regeneration across the DREZ. In marked contrast, simultaneous deletion of PTEN, but not SOCS3, dramatically enhanced kaBRAF-mediated regeneration enabling many more axons to penetrate the DREZ and grow deep into the spinal cord. This study shows that dual activation of BRAF-MEK-ERK and PI3K-Akt signaling is an effective strategy to stimulate robust intraspinal DR regeneration and may lead to recovery of sensory function after DR injury.
Temple University--Theses
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Manire, Meredith A. "ACTIVATING NEURON-INTRINSIC GROWTH PATHWAYS TO PROMOTE SPINAL CORD REGENERATION AFTER DORSAL ROOT INJURY". Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/585310.
Texto completo da fonteResumo:
Biomedical SciencesPh.D.;
Primary sensory axons fail to regenerate into the spinal cord following dorsal root injury leading to permanent sensory deficits. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Current approaches for promoting DR regeneration across the DREZ have had some success, but sustained, long-distance regeneration, particularly of large-diameter myelinated axons, still remains a formidable challenge. Our lab has previously shown that induced expression of constitutively active B-RAF (kaBRAF) enhanced the regenerative competence of injured DRG neurons in adult mice. In this study, I investigated whether robust intraspinal regeneration can be achieved by selective expression of kaBRAF alone or in combination with deletion of the myelin-associated inhibitors or neuron-intrinsic growth suppressors (PTEN or SOCS3). To this end, I used LSL-kaBRAF: brn3a-CreERT2 transgenic mice in which kaBRAF can be induced selectively in sensory neurons. I have also bred LSL-kaBRAF: brn3a-CreERT2 mice with triple knock-out mice lacking Nogo, Mag and OMgp or mouse lines carrying floxed alleles of PTEN or SOCS3. Single, double, and triple conditional mice were subjected to cervical DR crush and AAV2-eGFP vectors were used to selectively label regenerating axons of large-diameter neurons. I compared the extent of regeneration at 3 weeks or 2 months after DR injury using conventional anatomical and behavioral analyses. I found that kaBRAF alone promoted axon regeneration across the DREZ but did not produce significant functional recovery by two months. Supplementary deletion of Nogo, MAG, and OMgp did not improve kaBRAF-induced regeneration. Deletion of PTEN or SOCS3 individually or in combination failed to promote axon regeneration across the DREZ. In marked contrast, simultaneous deletion of PTEN, but not SOCS3, dramatically enhanced kaBRAF-mediated regeneration enabling many more axons to penetrate the DREZ and grow deep into the spinal cord. This study shows that dual activation of BRAF-MEK-ERK and PI3K-Akt signaling is an effective strategy to stimulate robust intraspinal DR regeneration and may lead to recovery of sensory function after DR injury.
Temple University--Theses
48
Jeffrey, N. D. "Behavioural consequences of demyelination and remyelination in the dorsal funiculus of the rat spinal cord". Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605078.
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This project aimed to investigate the behavioural effects of demyelination, spontaneous remyelination and transplant-mediated remyelination in the dorsal funiculus of the rat spinal cord. Neurological deficits were detected on a beam walking test after photochemical ablation of the dorsal funiculus of the rat lumbar spinal cord, suggesting the potential of this test for evaluation of demyelinating lesions. The severity of the locomotor deficits correlated with the extent of tissue destruction. When an intraspinal injection of ethidium bromide was used to induce a zone of demyelination in the dorsal funiculus of the cervical spinal cord there was impairment of locomotor efficiency during beam walking. The severity of locomotor impairment in this and most subsequent experiments was related to the size of the demyelinating lesion and the severity of axonal injury. Behavioural deficits resolved spontaneously so that recovery occurred by about 5 weeks post operatively. If remyelination was inhibited by exposure of the injected region to 40 Gray of x-irradiation behavioural recovery did not occur. In another group of rats, repeated injection of gliotoxin into a remyelinated ethidium bromide lesion caused recurrence of behavioural deficits. Injection of a mixed glial cell suspension into non-repairing (irradiated) ethidium bromide lesions initially did not produce superior behavioural recovery to that observed in control (non-transplanted) animals. However, transplantation into non-irradiated lesions did not prevent behavioural recovery. The study provides strong evidence that demyelination leads to loss of normal locomotor behaviour and that remyelination restores lost function. The failure to demonstrate conclusively that transplant-mediated remyelination restores function lost because of demyelination is probably the result of extensive axonal injury during lesioning and transplantation procedures.
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Goodman, Keiser Melanie Dawn. "Postsynaptic dorsal column spinal pathway does it play a role in cardiac pain? /". Oklahoma City : [s.n.], 2009.
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Brewer, Chelsie L. "Spinal inhibitory mechanisms controlling somatosensation: maturation and neonatal injury". University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1581333223198031.
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