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  • 1
    In: Organometallics, American Chemical Society (ACS), Vol. 29, No. 19 ( 2010-10-11), p. 4360-4368
    Type of Medium: Online Resource
    ISSN: 0276-7333 , 1520-6041
    RVK:
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2010
    detail.hit.zdb_id: 2006302-7
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Pain Vol. 160, No. 11 ( 2019-11), p. 2612-2623
    In: Pain, Ovid Technologies (Wolters Kluwer Health), Vol. 160, No. 11 ( 2019-11), p. 2612-2623
    Abstract: Nociceptive trigeminal afferents innervating craniofacial area, eg, facial skin and cranial meninges, project to a broad region in the medullary and upper cervical dorsal horn designated as the trigeminocervical complex. Lamina I neurons in the trigeminocervical complex integrate and relay peripheral inputs, thus playing a key role in both cranial nociception and primary headache syndromes. Because of the technically challenging nature of recording, the long-range trigeminal afferent inputs to the medullary and cervical lamina I neurons were not intensively studied so far. Therefore, we have developed an ex vivo brainstem–cervical cord preparation with attached trigeminal nerve for the visually guided whole-cell recordings from the medullary and cervical lamina I neurons. Two-thirds of recorded neurons generated intrinsic rhythmic discharges. The stimulation of the trigeminal nerve produced a complex effect; it interrupted the rhythmic discharge for hundreds of milliseconds but, if the neuron was silenced by a hyperpolarizing current injection, could elicit a discharge. The monosynaptic inputs from the trigeminal Aδ, high-threshold Aδ, low-threshold C, and C afferents were recorded in the medullary neurons, as well as in the cervical neurons located in the segments C1 to C2 and, to a lesser degree, in C3 to C4. This pattern of supply was consistent with our labelling experiments showing extensive cervical projections of trigeminal afferents. Excitatory inputs were mediated, although not exclusively, through AMPA/kainate and NMDA receptors, whereas inhibitory inputs through both GABA and glycine receptors. In conclusion, the trigeminocervical lamina I neurons receive a complex pattern of long-range monosynaptic and polysynaptic inputs from a variety of the trigeminal nociceptive afferents.
    Type of Medium: Online Resource
    ISSN: 0304-3959 , 1872-6623
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1494115-6
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  • 3
    In: Pain, Ovid Technologies (Wolters Kluwer Health), Vol. 157, No. 2 ( 2016-02), p. 475-487
    Type of Medium: Online Resource
    ISSN: 0304-3959
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1494115-6
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2004
    In:  The Journal of Physiology Vol. 559, No. 2 ( 2004-09), p. 383-395
    In: The Journal of Physiology, Wiley, Vol. 559, No. 2 ( 2004-09), p. 383-395
    Abstract: Using tight‐seal recordings from rat spinal cord slices, intracellular labelling and computer simulation, we analysed the mechanisms of spike frequency adaptation in substantia gelatinosa (SG) neurones. Adapting‐firing neurones (AFNs) generated short bursts of spikes during sustained depolarization and were mostly found in lateral SG. The firing pattern and the shape of single spikes did not change after substitution of Ca 2+ with Co 2+ , Mg 2+ or Cd 2+ indicating that Ca 2+ ‐dependent conductances do not contribute to adapting firing. Transient K A current was small and completely inactivated at resting potential suggesting that adapting firing was mainly generated by voltage‐gated Na + and delayed‐rectifier K + (K DR ) currents. Although these currents were similar to those previously described in tonic‐firing neurones (TFNs), we found that Na + and K DR currents were smaller in AFNs. Discharge pattern in TFNs could be reversibly converted into that typical of AFNs in the presence of tetrodotoxin but not tetraethylammonium, suggesting that lower Na + conductance is more critical for the appearance of firing adaptation. Intracellularly labelled AFNs showed specific morphological features and preserved long extensively branching axons, indicating that smaller Na + conductance could not result from the axon cut. Computer simulation has further revealed that down‐regulation of Na + conductance represents an effective mechanism for the induction of firing adaptation. It is suggested that the cell‐specific regulation of Na + channel expression can be an important factor underlying the diversity of firing patterns in SG neurones.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    American Physiological Society ; 2004
    In:  Journal of Neurophysiology Vol. 91, No. 2 ( 2004-02), p. 646-655
    In: Journal of Neurophysiology, American Physiological Society, Vol. 91, No. 2 ( 2004-02), p. 646-655
    Abstract: Ionic conductances underlying excitability in tonically firing neurons (TFNs) from substantia gelatinosa (SG) were studied by the patch-clamp method in rat spinal cord slices. Ca 2+ -dependent K + (K CA ) conductance sensitive to apamin was found to prolong the interspike intervals and stabilize firing evoked by a sustained membrane depolarization. Suppression of Ca 2+ and K CA currents, however, did not abolish the basic pattern of tonic firing, indicating that it was generated by voltage-gated Na + and K + currents. Na + and K + channels were further analyzed in somatic nucleated patches. Na + channels exhibited fast activation and inactivation kinetics and followed two-exponential time course of recovery from inactivation. The major K + current was carried through tetraethylammonium (TEA)-sensitive rapidly activating delayed-rectifier (K DR ) channels with a slow inactivation. The TEA-insensitive transient A-type K + (K A ) current was very small in patches and was strongly inactivated at resting potential. Block of K DR rather than K A conductance by 1 mM TEA lowered the frequency and stability of firing. Intracellular staining with biocytin revealed at least three morphological groups of TFNs. Finally, on the basis of present data, we created a model of TFN and showed that Na + and K DR currents are sufficient to generate a basic pattern of tonic firing. It is concluded that the balanced contribution of all ionic conductances described here is important for generation and modulation of tonic firing in SG neurons.
    Type of Medium: Online Resource
    ISSN: 0022-3077 , 1522-1598
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2004
    detail.hit.zdb_id: 80161-6
    detail.hit.zdb_id: 1467889-5
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2004
    In:  Anesthesiology Vol. 101, No. 5 ( 2004-11-01), p. 1177-1183
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 5 ( 2004-11-01), p. 1177-1183
    Abstract: Spinal substantia gelatinosa (SG) is a site of action of administered and endogenous opioid agonists and is an important element in the system of antinociception. However, little is known about the types of neurons serving as specific postsynaptic targets for opioid action within the SG. To study the spinal mechanisms of opioidergic analgesia, the authors compared the action of mu-opioid agonist [D-Ala, N-Me-Phe, Gly-ol]-enkephalin (DAMGO) on SG neurons with different intrinsic firing properties. Methods Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the sensitivity of SG neurons to DAMGO. Results Three groups of neurons with distinct distributions in SG were classified: tonic-, adapting-, and delayed-firing neurons. DAMGO at 1 microm concentration selectively hyperpolarized all tonic-firing neurons tested, whereas none of the adapting- or delayed-firing neurons were affected. The effect of DAMGO on tonic-firing neurons was due to activation of G protein-coupled inward-rectifier K conductance, which could be blocked by 500 microm Ba and 500 microm Cs but increased by 50 microm baclofen. As a functional consequence of DAMGO action, a majority of tonic-firing neurons changed their pattern of intrinsic firing from tonic to adapting. Conclusions It is suggested that tonic-firing neurons, presumably functioning as excitatory interneurons, are primary postsynaptic targets for administered and endogenous opioid agonists in spinal SG. Functional transition of cells in this group from tonic to adapting firing mode may represent an important mechanism facilitating opioidergic analgesia.
    Type of Medium: Online Resource
    ISSN: 0003-3022
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
    detail.hit.zdb_id: 2016092-6
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  • 7
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 5 ( 2022-06-03), p. 1632-1640
    Abstract: The axon initial segment is a specialized compartment of the proximal axon of CNS neurons where action potentials are initiated. However, it remains unknown whether this domain is assembled in sensory dorsal root ganglion neurons, in which spikes are initiated in the peripheral terminals. Here we investigate whether sensory neurons have an axon initial segment and if it contributes to spontaneous activity in neuropathic pain. Our results demonstrate that myelinated dorsal root ganglion neurons assemble an axon initial segment in the proximal region of their stem axon, enriched in the voltage-gated sodium channels Nav1.1 and Nav1.7. Using correlative immunofluorescence and calcium imaging, we demonstrate that the Nav1.7 channels at the axon initial segment are associated with spontaneous activity. Computer simulations further indicate that the axon initial segment plays a key role in the initiation of spontaneous discharges by lowering their voltage threshold. Finally, using a Cre-based mouse model for time-controlled axon initial segment disassembly, we demonstrate that this compartment is a major source of spontaneous discharges causing mechanical allodynia in neuropathic pain. Thus, an axon initial segment domain is present in sensory neurons and facilitates their spontaneous activity. This study provides a new insight in the cellular mechanisms that cause pathological pain and identifies a new potential target for chronic pain management.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 1995
    In:  Pflügers Archiv European Journal of Physiology Vol. 430, No. 6 ( 1995-10), p. 879-886
    In: Pflügers Archiv European Journal of Physiology, Springer Science and Business Media LLC, Vol. 430, No. 6 ( 1995-10), p. 879-886
    Type of Medium: Online Resource
    ISSN: 0031-6768 , 1432-2013
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1995
    detail.hit.zdb_id: 1463014-X
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Society for Neuroscience ; 2022
    In:  The Journal of Neuroscience Vol. 42, No. 17 ( 2022-04-27), p. 3587-3598
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 42, No. 17 ( 2022-04-27), p. 3587-3598
    Abstract: Cervical and trigeminal afferents innervate neighboring cranial territories, and their convergence on upper cervical dorsal horn neurons provides a potential substrate for pain referral in primary headache syndromes. Lamina I neurons are central to this mechanism, as they relay convergent nociceptive input to supraspinal pain centers. Unfortunately, little is known about the interactions between trigeminal and cervical afferents supplying Lamina I neurons. Here, we used rats of both sexes to show that cervical and trigeminal afferents interact via presynaptic inhibition, where monosynaptic inputs to Lamina I neurons undergo unidirectional as well as reciprocal presynaptic control. This means that afferent-driven presynaptic inhibition shapes the way trigeminal and cervical Aδ-fiber and C-fiber input reaches Lamina I projection neurons (PNs) and local-circuit neurons (LCNs). We propose that this inhibition provides a feedforward control of excitatory drive to Lamina I neurons that regulates their convergent and cervical-specific or trigeminal-specific processing modes. As a consequence, disruption of the trigeminal and cervical afferent-driven presynaptic inhibition may contribute to development of primary headache syndromes. SIGNIFICANCE STATEMENT Cervical and trigeminal afferents innervate neighboring cranial territories, and their convergence on upper cervical dorsal horn neurons provides a potential substrate for pain referral in primary headache syndromes. Lamina I neurons are central to this mechanism as they relay convergent nociceptive input to supraspinal pain centers. Here, we show that cervical and trigeminal afferents interact via presynaptic inhibition, where inputs to Lamina I neurons undergo unidirectional as well as reciprocal control. The afferent-driven presynaptic inhibition shapes the trigeminocervical Aδ-fiber and C-fiber input to Lamina I neurons. This inhibition provides control of excitatory drive to Lamina I neurons that regulates their convergent and cervical-specific or trigeminal-specific processing modes. Disruption of this control may contribute to development of primary headache syndromes.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2022
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    American Physiological Society ; 2008
    In:  Journal of Neurophysiology Vol. 99, No. 2 ( 2008-02), p. 617-628
    In: Journal of Neurophysiology, American Physiological Society, Vol. 99, No. 2 ( 2008-02), p. 617-628
    Abstract: Thin afferent axons conduct nociceptive signals from the periphery to the spinal cord. Their somata express two classes of Na + channels, TTX-sensitive (TTX-S) and TTX-resistant (TTX-R), but their relative contribution to axonal conduction and synaptic transmission is not well understood. We studied this contribution by comparing effects of nanomolar TTX concentrations on currents associated with compound action potentials in the peripheral and central branches of Aδ- and C-fiber axons as well as on the Aδ- and C-fiber-mediated excitatory postsynaptic currents (EPSCs) in spinal dorsal horn neurons of rat. At room temperature, TTX completely blocked Aδ-fibers (IC 50 , 5–7 nM) in dorsal roots (central branch) and spinal, sciatic, and sural nerves (peripheral branch). The C-fiber responses were blocked by 85–89% in the peripheral branch and by 65–66% in dorsal roots (IC 50 , 14–33 nM) with simultaneous threefold reduction in their conduction velocity. At physiological temperature, the degree of TTX block in dorsal roots increased to 93%. The Aδ- and C-fiber-mediated EPSCs in dorsal horn neurons were also sensitive to TTX. At room temperature, 30 nM blocked completely Aδ-input and 84% of the C-fiber input, which was completely suppressed at 300 nM TTX. We conclude that in mammals, the TTX-S Na + channels dominate conduction in all thin primary afferents. It is the only type of functional Na + channel in Aδ-fibers. In C-fibers, the TTX-S Na + channels determine the physiological conduction velocity and control synaptic transmission. TTX-R Na + channels could not provide propagation of full-amplitude spikes able to trigger synaptic release in the spinal cord.
    Type of Medium: Online Resource
    ISSN: 0022-3077 , 1522-1598
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 80161-6
    detail.hit.zdb_id: 1467889-5
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