Gerincvelői neuronhálózatok szerveződése, pre- és posztnatális fejlődése, és plasztikus változásai neuropátiás és gyulladásos fájdalom modellekben
Title in English
Organization, pre- and postnatal development of spinal neural circuits, and their plasticity in neuropathic and inflammatory pain states
Panel
Neurosciences
Department or equivalent
Department of Anatomy, Histology and Embryology (University of Debrecen)
Participants
Eördögh, Mária Muszil, Dóra Papp, Ildikó Petkó, Mihály Szabó, Zoltán Szokol, Karolina Szűcs, Péter Veress, Gábor
Starting date
2004-01-01
Closing date
2007-12-31
Funding (in million HUF)
16.770
FTE (full time equivalent)
0.00
state
closed project
Final report
Results in Hungarian
A pályázat célul tűzte ki a gerincvelői nociceptív ingerületfeldolgozást végző és a gerincvelői szintű motoros működéseket irányító neuronhálózatok szerveződésének, kémiai tulajdonságainak, és fájdalom modellekben mutatott plaszticitásának vizsgálatát. Ennek megfelelően vizsgáltuk a nociceptív primer afferensek és a gerincvelői hátsó szarvi másodlagos érző neuronok közötti szinaptikus kapcsolatok molekuláris anatómiáját; a gerincvelő hátsó szarvi propriospinalis neuronok szinaptikus kapcsolatait, fiziológiai és neurokémiai tulajdonságait; a gerincvelő hátsó szarvi neuronhálózatok plaszticitását gyulladásos fájdalom modellben; és a gerincvelői motoros működések szabályozásában résztvevő premotor interneuronok neurokémiai tulajdoságait. Eredményeink jelentős mértékben hozzájárultak a gerincvelői neuronok morfológia, fiziológiai és neurokémiai tulajdonságainak pontosabb megértéséhez, és ezen keresztül ahhoz, hogy pontosabb képet alkothassunk a gerincvelői neuronoknak a nociceptív és motoros feladatok kivitelezésében betöltött szerepéről. Eredményeink hozzájárultak a fájdalomérzet kiváltásában szerepet játszó gerincvelői szintű szenzoros ingerület feldolgozási folyamatok pontosabb megértéséhez. Rávilágítottuk a figyelmet olyan molekulákra, amelyek eddig nem kaptak megfelelő figyelmet a fájdalomkutatásban. Eredeti megfigyeléseink kiindulópontul szolgálhatnak újabb, az eddigieknél hatékonyabb és kevésbe addiktív fájdalomcsillapító eljárások kidolgozásához.
Results in English
The aim of the project was to investigate the organization and neurochemical properties of spinal neural circuits underlying nociceptive information processing and motor control. In addition, we also intended to study the plasticity of sensory neural microcircuits of the superficial spinal dorsal horn evoked by inflammatory chronic pain. Thus, we investigated the molecular anatomy of synaptic contacts between axon terminals of nociceptive primary afferents and secondary sensory spinal neurons; synaptic interconnectivity, physiological and neurochemical properties of propriospinal neuron in the superficial spinal dorsal horn; plasticity of spinal neural microcircuits evoked by chronic subcutaneous inflammation; and the chemical properties of premotor interneurons participating in the coordination of spinal motor activities. Our results provided a substantial contribution to the understanding of the morphological, physiological and neurochemical properties of spinal neurons, and also enabled us to obtain a better understanding about nociceptive and motor activities at the level of the spinal cord. We provided new insights into the organization of pain processing spinal microcircuits, fundamental mechanisms of activity-evoked neural plasticity. We have described molecular mechanisms that have not received enough attention in pain research till now. Our original observations may assist in developing effective therapeutic strategies for chronic pain syndromes.
Papp I; Veress G; Bahaerguli N; Vereb Gy; Antal M: Expression of hyperpolarization-activated and cyclic nucleotid-gated cation channel subunit 2 in axon terminals of peptidergic nociceptive primary sensory neurons in the superficial spinal dorsal horn of rats, Clin Neurosci 57, Suppl 1: 53, 2004
Antal M; Veress G; Papp I: Postsynaptic targets of peptidergic nociceptive primary afferents that express hyperpolarization-activated and cyclic nucleotid-gated cation channel subunit 2 in laminae I-IIo of the rat spinal dorsal horn, Forum Eur Neurosci Abstr 4: 189, 2004
Szokol K; Szűcs P; Veress G; Antal M; Poisbeau P: NK1 receptor mediated increase of inhibitory input to lamina VII neurons, Clin Neurosci 57, Suppl 1: 66, 2004
Veress G; Friedlander E; Vereb Gy; Antal M: The CB1 cannabinoid receptor is present in substance P containing peptidergic primary afferents in the dorsal horn of the spinal cord of the rat, Forum Eur Neurosci Abstr 4: 110, 2004
Wéber I; Birinyi A; Shupliakov O; Antal M: Colocalization of zinc with GABA and glycine in the spinal cord, Clin Neurosci 57, Suppl 1: 72, 2004
Eördögh M; Veress G; Antal M: Colocalization of GluR1 and GluR2 subunits of AMPA receptors and neurokinin-1 receptor in laminae I-II of the rat lumbar spinal cord, Clin Neurosci 57, Suppl 1: 16, 2004
Muszil D; Veress G; Antal M: Changes in the distribution and co-localization of NK1R and GluR1 in the rat superficial dorsal horn evoked by inflammation of the hindpaw, Clin Neurosci 57, Suppl 1: 48, 2004
Coelho H; Antal M: Programmed cell death of interneuronsin the embryonic chick lumbosacral spinal cord., Clin Neurosci 58, Suppl.1: 20, 2005
Muszil D; Németh Cs; Veress G; Szűcs P; Antal M: Altered GABA synthesis in the spinal dorsal horn and its potential effect on primary afferent terminals in Freund’s adjuvant induced inflammation, Clin Neurosci 58, Suppl.1: 68, 2005
Papp I; Veress G; Antal M: Presynaptic properties and postsynaptic targets of peptidergic nociceptive primary afferents that express HCN channel subunit 2 in laminae I-II of the spinal dorsal horn, Clin Neurosci 58, Suppl.1: 74, 2005
Petkó M; Veress G; Antal M: Commissural propriospinal connections between the lateral aspects of laminae II-IV in the lumbar spinal cord, Clin Neurosci 58, Suppl.1: 76, 2005
Szűcs P; Szokol K; Antal M: Effect of HCN2 channels on synaptic transmission between C/A-delta primary afferents and lamina II neurons of the rat spinal cord, Clin Neurosci 58, Suppl.1: 93, 2005
Wéber I; Veress G; Szűcs P; Vereb Gy; Antal M; Birinyi A: Neurotransmitters of commissural interneurons in the lumbar spinal cord of neonatal rats, Clin Neurosci 58, Suppl.1: 105, 2005
Antal M; Szűcs P; Holló K; Veress G; Erdélyi F; Szabó G; Papp I: HCN2 channels modulate synaptic transmission from peptidergic nociceptive primary afferents to secondary sensory neurons in laminae I-IIo of the rat spinal dorsal horn, Soc Neurosci Abstr 171.8, 2005
Muszil D; Veress G; Antal M: Changes in the expression of AMPA receptor subunits in the mouse superficial spinal dorsal horn in inflammatory pain, Clin Neurosci 59: Suppl. 1, 48, 2006
Németh Cs; Muszil D; Szűcs P; Veress G; Antal M: GABA-B receptor expression of primary afferent fibers in the superficial dorsal horn in CFA induced peripheral inflammation, Clin Neurosci 59: Suppl. 1, 49, 2006
Petkó M; Veress G; Antal M: Synaptic relations and neurochemical properties of the medio-lateral propriospinal projection of laminae I-IV in the lumbar spinal cord, Clin Neurosci 59: Suppl. 1, 54, 2006
Szűcs p; Antal Zs; Antal M: Lamotrigine effectively blocks synaptic transmission between nociceptive primary afferents and secondary sensory neurons of the spinal dorsal horn, Clin Neurosci 59: Suppl. 1, 63, 2006
Antal M; Fukazawa Y; Eördögh M; Shigemoto R: Numbers, densities and colocalization of AMPA and NMDA receptors at individual synaptic contact areas in the superficial spinal dorsal horn, Eur J Pain 11, Suppl 1: S150-151, 2007
Papp I; Antal M: Expression of HCN2 ion channels in the superficial spinal dorsal horn of rats in Freund's adjuvant-induced inflammatory pain condition, Clin Nweurosci 60, Suppl 1: 51, 2007
Antal M; Papp I; Bahaerguli N; Veress G; Vereb Gy: Expression of hyperpolarization-activated and cyclic nucleotid-gated cation channel subunit 2 in axon terminals of peptidergic nociceptive primary sensory neurons in the, Eur J Neurosci 19: 1336-1342, 2004
Petkó M; Veress G; Vereb Gy; Storm-Mathisen J; Antal M: Commissural propriospinal connections between the lateral aspects of laminae III-IV in the lumbar spinal cord of rats, J Comp Neurol 480: 364-377, 2004
Melnick IV; Santos S; Szokol K; Szűcs P; Safranov BV: Ionic basis of tonic firing in spinal substantia gelatinosa neurons of rat, J Neurophysiol 91: 646-655, 2004
Hughes DI; Mackie M; Nagy GG; Riddell JS; Maxwell DJ; Szabó G; Erdélyi F; Veress G; Szűcs P; Antal M; Todd AJ: P boutons in lamina IX of the rodent spinal cord express high levels of glutamic acid decarboxilase-65 and originate from cells in deep medial dorsal horn, Proc Natl Acad Sci 102: 9038-9043, 2005
Papp I; Szűcs P; Holló K; Erdélyi F; Szabó G., Antal M: yperpolarization-activated and cyclic nucleotid-gated cation channel subunit 2 ion channels modulate synaptic transmission from nociceptive primary afferents containing s, Eur J Neurosci 24: 1341-1352, 2006
Wéber I; Veress G; Szűcs P; Antal M; Birinyi A: Neurotransmitter systems of commissural interneurons in the lumbar spinal cord of neonatal rats, Brain Res 1178: 65-72, 2007
Wéber I; Pukár Z; Kozák N; Antal M: Projections of primary afferent fibers to last-order premotor interneurons in the lumbar spinal cord of rats, Brain Res Bull 71: 337-343, 2007
Szűcs P; Szokol K; Veress G; Antal M; Poisbeau P: Modulation of neuronal excitability by substance P in neurons of laminae V-VII of the neonatal spinal cord, Forum Eur Neurosci Abstr 4: 107, 2004
Antal M; Eördögh M; Fukazawa Y; Shigemoto R: Numbers, densities and colocalization of AMPA- and NMDA-type glutamate receptors at individual synaptic contact areas in the superficial spinal dorsal horn of rats, Soc Neurosci Abstr 822.14, 2007
Muszil D; Veress G; Antal M;: Distribution of potassium-chloride cotransporter 2 (KCC2) in the superficial spinal dorsal horn, Clin Neurosci 60, Suppl 1: 46, 2007
