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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 19 (2004), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Activation of voltage-dependent Ca2+ channels (VDCCs) is critical for neurotransmitter release, neuronal excitability and postsynaptic Ca2+ signalling. Antagonists of VDCCs can be antinociceptive in different animal pain models. Neurons in lamina I of the spinal dorsal horn play a pivotal role in the processing of pain-related information, but the role of VDCCs to the activity-dependent Ca2+ increase in lamina I neurons and to the synaptic transmission between nociceptive afferents and second order neurons in lamina I is not known. This has now been investigated in a lumbar spinal cord slice preparation from young Sprague–Dawley rats. Microfluorometric Ca2+ measurements with fura-2 have been used to analyse the Ca2+ increase in lamina I neurons after depolarization of the cells, resulting in a distinct and transient increase of the cytosolic Ca2+ concentration. This Ca2+ peak was reduced by the T-type channel blocker, Ni2+, by the L-type channel blockers, nifedipine and verapamil, and by the N-type channel blocker, ω-conotoxin GVIA. The P/Q-type channel antagonist, ω-agatoxin TK, had no effect on postsynaptic [Ca2+]i. The NMDA receptor channel blocker D-AP5 reduced the Ca2+ peak, whereas the AMPA receptor channel blocker CNQX had no effect. Postsynaptic currents, monosynaptically evoked by electrical stimulation of the attached dorsal roots with C-fibre and Aδ-fibre intensity, respectively, were reduced by N-type channel blocker ω-conotoxin GVIA and to a much lesser extent, by P/Q-type channel antagonist ω-agatoxin TK, and the L-type channel blockers verapamil, respectively. No difference was found between unidentified neurons and neurons projecting to the periaqueductal grey matter. This is the first quantitative description of the relative contribution of voltage-dependent Ca2+ channels to the synaptic transmission in lamina I of the spinal dorsal horn, which is essential in the processing of pain-related information in the central nervous system.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Long-term potentiation (LTP) of spinal C-fibre-evoked field potentials can be induced by brief electrical stimulation of afferent C-fibres, by natural noxious stimulation of skin or by acute nerve injury. Here, we report that in urethane anaesthetized, adult rats prolonged high frequency burst stimulation of the sciatic nerve at Aδ-fibre strength produced long-term depression (LTD) of C-fibre-evoked field potentials, and also depressed the increased amplitudes of C-fibre-evoked field potentials recorded after LTP had been established (depotentiation). Electrical stimulation of Aβ-fibres failed to induce LTD or depotentiation. In spinalized rats, prolonged Aδ-fibre conditioning stimulation induced LTP rather than LTD of C-fibre-evoked field potentials. Thus, tonic descending inhibition may determine the direction of plastic changes in C-fibre-mediated synaptic transmission. Spinal application of the N-methyl-d-aspartic acid receptor antagonist D-APV blocked induction of LTD in intact rats and LTP in spinalized rats. The presently described LTD and the depotentiation of established LTP of C-fibre-evoked field potentials in spinal dorsal horn may underlie some forms of prolonged analgesia induced by peripheral nerve stimulation procedures.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 6 (1994), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Peripheral noxious stimulation leads to a rapid and transient expression of c-fos, c-jun and other immediate-early genes (IEGs) in the spinal cord. However, the role of IEG encoded transcription factors in plasticity of spinal neurons remains speculative. In the present study we have shown that superfusion of rat spinal cord with antisense oligodeoxynucleotides complementary to c-fos mRNA suppresses heat-induced c-Fos protein expression without affecting other members of the Fos and Jun family, thus providing a technique to determine the function of IEGs in vivo.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 68 (1990), S. 125-128 
    ISSN: 1432-1440
    Keywords: B-vitamins ; Spinal dorsal horn ; Afferent inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Afferent inhibition of spinal dorsal horn neuronal responses to noxious skin heating was induced by transcutaneous electrical nerve stimulation in pentobarbital-anesthetized rats. Pretreatment with B vitamins significantly enhanced this afferent inhibition, possibly due to an increase in the synthesis rate of inhibitory neurotransmitters in central neurones.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: Dorsal horn neuron ; Descending inhibition ; EEG synchronization ; Subcortical forebrain ; Basal forebrain ; Nociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In cats anaesthetized with sodium pentobarbital and 70% N2O, single lumbar dorsal horn neurons were excited by controlled noxious radiant heating of glabrous hindpaw skin. The EEG was recorded from the pericruciate cortex and posterior lateral gyrus. Subcortical forebrain sites where electrical stimulation inhibited dorsal horn neuronal heat-evoked responses contralaterally were identified by mapping the caudate nucleus, internal capsule, septum, nucleus accumbens and basal forebrain regions. Inhibitory sites were mainly located in the ventral forebrain (ventral septum, diagonal band, basal forebrain). The caudate nucleus and internal capsule had a low incidence and effectiveness of inhibitory sites. In the basal forebrain, the incidence and effectiveness of inhibitory sites decreased from caudal to rostral regions. There was a rostral limit of inhibitory sites, both medially and laterally. The magnitude of inhibition increased with graded increases in brain stimulation intensity. The mean incremental increase in inhibition was greater for caudal than for rostral basal forebrain sites. Mean stimulus currents for threshold of inhibition and for inhibition to 50% of control heat responses were lower for caudal than for rostral sites. Responses of the dorsal horn neurons to increasing temperatures of noxious skin heating were monotonic linear functions over the temperature range studied (48–53° C). Stimulation in both rostral and caudal basal forebrain decreased the slope of this stimulus-response function, with a greater decrease for caudal sites. Cortical EEG synchronization was evoked by stimulation in the caudate nucleus and rostral basal forebrain. For both regions, most synchronogenic sites did not produce descending inhibition of dorsal horn neurons. The significance of these findings in relation to descending inhibition from other brain regions and stimulation-produced analgesia is discussed.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: CNS-blocks ; Reversible inactivation ; Functional anatomy ; Lidocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The time course and extent of local anaesthetic blocks within the spinal cord of cats were evaluated. A monopolar stimulation electrode with the tip lowered into the dorsal columns (DC) 1000 μm below cord surface was used to activate antidromically DC fibers at the T13 level and evoke cord dorsum potentials at the level of the lumbar spinal cord. The amplitude of the negative deflection, the N-wave, was determined for various stimulation intensities (stimulation-response-function, SRF). Lidocaine (1%) was microinjected in volumes of 0.5 or 1.0 μl into the DC from a glass micropipette 1 mm caudal to the stimulation site. Conduction block was characterized by a reversible shift of the SRFs to higher stimulation intensities. The diameter of the blocked area in the transverse plane was evaluated from threshold intensities and was found to be 0.9±0.1 mm 4 to 30 min after the injection of 0.5 μl lidocaine and 1.6±0.36 mm 10 to 45 min after the injection of 1.0 μl lidocaine. In the sagittal plane, the diameter of the blocked area following 1.0 μl lidocaine was found to be up to 2.8 mm. The DC-block was reversible within 92 min following injection of 1.0 μl and 69 min after the injection of 0.5 μl lidocaine. The application of the present findings for blocks in other CNS structures is discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 14 (2000), S. 297-301 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Neurobiologie ; Entwicklung ; Schmerzgedächtnis ; Sensibilisierung ; Schmerzhemmung ; Keywords Neurobiology ; Development ; Sensitization ; Pain ; Descending inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. The somatosensory system of preterms and newborns differs substantially from adults. These differences are of considerable preclinical and clinical interest. Maturation of A- and C-fibre synaptic connections in the dorsal horn and development of descending inhibition from the brainstem all take place postnatally in the rat. In early stages of development there is no definite spatial sepraration in the dorsal horn between the nociceptive and the non-nociceptive system. In preterms but not in adults non-noxious stimuli can induce central sensitization. Many neurotransmitters and signalling molecules involved in pain pathways are expressed early in the developing nervous system but do not reach adult levels for a considerable period. More important, receptors are frequently transiently overexpressed or expressed in areas during development where they are not seen in the adult and may have a different functional profile. The descending pain inhibitory system that provides an important protection against central sensitization developes later than the ascending nociceptive system. Thus, during a critical period of time the immature nociceptive system is highly vulnerable. For example, neonatal circumcision in the absence of analgesia results in increased pain responses during subsequent routine vaccination months later. Conclusions. In view of the changing nature of neonatal somatosensory and pain pathways and the vulnerability of the developing nervous system to alterations in sensory stimulation it is important that preterms and newborns need the care of a specialist for prevention and treatment of pain to avoid suffer and long-term changes in the nervous system.
    Notes: Zusammenfassung Hintergrund. Das somatosensorische System weist bei Früh- und Neugeborenen eine Reihe von Besonderheiten auf, die von erheblicher präklinischer und klinischer Bedeutung sind. So sind zunächst nozizeptives und nichtnozizeptives System im Rückenmark noch nicht streng voneinander getrennt. Das hat zur Folge, dass bei Frühgeborenen niederschwellige Reize Sensibilisierungsmechanismen auslösen können, wie sie bei Erwachsenen nur durch starke Schmerzreize möglich sind. Exzitatorische und inhibitorische Neurotransmittersysteme reifen zu unterschiedlichen Zeitpunkten und die Entwicklung der körpereigenen Schmerzabwehr erfolgt später als die des nozizeptiven Systems. In einer kritischen Periode fehlt daher der wichtigste Schutzmechanismus vor peripheren und zentralen Sensibilisierungsmechanismen. Daher müssen besondere präventive Maßnahmen ergriffen werden. Schlussfolgerungen. Früh- und Neugeborene benötigen eine besonders qualifizierte Schmerzprävention und Schmerztherapie, damit Leiden und lang anhaltende Schäden sicher vermieden werden.
    Type of Medium: Electronic Resource
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