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  • 1
    Electronic Resource
    Electronic Resource
    Was ist ein Nozizeptor? (1997)
    Springer
    Der Anaesthesist 46 (1997), S. 142-153 
    Details
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Sinnesrezeptor ; Nozisensor ; Schmerzempfindung ; Freie Nervenendigung ; Aδ- und C-Fasern ; Noxischer Reiz ; Polymodaler Nozizeptor ; Schlafender Nozizeptor ; Chemonozizeption ; Sensorische Endigung ; Rezeptive Abschnitte ; Neurogene Entzündung ; Antinozizeptive Therapie ; Key words Sensory receptor ; Nocisensor ; Pain ; Free nerve ending ; Aδ and C fibres ; Noxious stimulus ; Polymodal nociceptor ; Silent nociceptor ; Sensitisation ; Sensory ending ; Receptive sites ; Neurogenic inflammation ; Antinociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Introduction: Nociceptors can be defined as sensory receptors that are activated by noxious stimuli that damage or threaten the body’s integrity. Nociceptors belong to the slowly conducting afferent Aδ and C fibres. They are classified according to their responses to mechanical, thermal, and chemical stimuli. Skin nociceptors: In the skin, high-threshold mechano-nociceptors (HTMs) and mechano-heat nociceptors of A and C fibres (AMHs and CMHs) are frequently found. CMHs are usually called polymodal C fibres (CPMs) if they also show chemosensitive properties. Sensations of sharp pain are evoked by intraneural microstimulation of nociceptive Aδ fibres, whereas stimulation of C fibres causes dull pain sensations. Nociceptors of deep tissues and viscera: Slowly conducting afferents of deep tissues (muscles, joints) are primarily classified according to their mechanosensitivity. High-threshold afferents in somatic and visceral tissues are specifically activated by noxious mechanical stimuli. Many visceral afferents, however, are already activated by peristaltic contractions encoding the stimulus intensity over a wide range. High proportions of somatic and visceral nociceptors can be excited or sensitised by various irritants and inflammatory mediators such as capsaicin, bradykinin, prostaglandins, leukotrienes, serotonin, histamine, and free radicals. As a special class of nociceptors, mechano-insensitive or „silent” afferents have been found in nearly all tissues. Silent afferents become mechanosensitive only after long noxious stimulation, e.g., during an inflammation. Free nerve endings:„Free nerve endings”, which are regarded as the morphological correlatives of nociceptors, usually consist of bundles of unmyelinated fibres. With electron microscopy varicose segments of the sensory axon are visible that are characterised by free areas of axolemma, accumulations of mitochondria and vesicles, and a modified axoplasm. These presumptive receptive sites are periodically arranged along the whole course of the sensory endings at a length of up to several hundred microns. Additionally, the fine sensory endings are branched, forming tree-like structures, and frequently innervate different types of tissues. Studies correlating structure and function of articular afferents provide evidence for a close relationship between topographical and functional properties of sensory endings. High-threshold afferents (nociceptors) seem to terminate in structures of dense connective tissue. Proportions of nociceptors contain neuropeptides such as substance P and calcitonin gene- related peptide, which are released from the activated nociceptive terminals and cause neurogenic inflammation, including precapillary vasodilatation and postcapillary plasma extravasation. Pain treatment: Experimental and clinical progress has been achieved in using the nociceptor as a target for chemical antinociception and treatment of pain. Substances that act directly or indirectly on the nociceptor are steroidal and non-steroidal analgesics, capsaicin analogs, bradykinin antagonists, opioids, and (in the trigeminal system) 5-hydroxytryptamine agonists.
    Notes: Zusammenfassung Einleitung: Nozizeptoren sind Sinnesrezeptoren für noxische (den Organismus schädigende oder bedrohende) Stimuli. Sie gehören zu den langsam leitenden Afferenzen der Gruppen III (Aδ-) und IV (C-Fasern) und werden funktionell nach ihren Antworteigenschaften bei mechanischer, thermischer und chemischer Stimulation klassifiziert. Nozizeptoren der Haut: In der Haut unterscheidet man hochschwellige Mechano- Nozizeptoren (high-threshold mechano- nociceptors, HTMs), welche vorwiegend von Aδ-Fasern gebildet werden, von mechano- und hitzesensiblen Nozizeptoren, die entweder zu den Aδ- (A mechano-heat nociceptors, AMHs) oder den C-Afferenzen (C mechano-heat nociceptors, CMHs) gerechnet werden. Intraneurale Mikrostimulation von nozizeptiven Aδ-Fasern der Haut ruft eine scharfe, Stimulation von C-Fasern eine dumpfe Schmerzempfindung hervor. Nozizeptoren des tiefen Gewebes und der Viszera: Aδ- und C-Afferenzen der tiefen Gewebe (Muskeln, Gelenke) werden vorwiegend nach ihrer Mechanosensibilität klassifiziert; hochschwellige Afferenzen sind nur durch noxische mechanische Stimuli erregbar (Spezifitätskonzept der Nozizeption). Obwohl auch ein kleiner Teil der viszeralen Nozizeptoren mechanisch hochschwellig ist, werden die meisten bereits durch normale peristaltische Kontraktionen erregt und folgen somit mehr einem Intensitätskonzept. Eine besondere Klasse von Nozizeptoren stellen mechanisch insensible oder „schlafende” Nozizeptoren dar. Sie werden erst bei langdauernden noxischen Ereignissen wie z.B. einer Entzündung mechanosensitiv. Freie Nervenendigungen: Die sog. „freien Nervenendigungen”, die als morphologisches Korrelat der Nozizeptoren angesehen werden, bestehen meist aus Bündeln unmyelinisierter Nervenfasern, welche bäumchenartig verzweigt sind. Mutmaßlich rezeptive Stellen finden sich entlang der Verzweigungen des gesamten „sensorischen Endbäumchens”. In einem Teil der Nozizeptoren wurden „sensorische” Neuropeptide wie Substanz P und CGRP nachgewiesen, welche bei Erregung der Nervenfasern freigesetzt werden und zu einer neurogenen Entzündung mit präkapillärer Vasodilatation und postkapillärer Plasmaextravasation führen. Schmerztherapie: Mit dem Ziel einer peripher wirkenden Pharmakotherapie von Schmerzen wird experimentell und klinisch versucht, die Aktivität des nozizeptiven Systems auf der Ebene der Nozizeptoren zu hemmen. Zu den direkt oder indirekt am Nozizeptor wirkenden Substanzen gehören steroidale und nicht-steroidale Analgetika, Capsaicin-Analoga, Bradykinin-Antagonisten, Opioide und (im trigeminalen System) 5-HT1-Agonisten.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001010050384
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  • 2
    Electronic Resource
    Electronic Resource
    Morphological characteristics of the innervation of the cat's knee joint (1988)
    Springer
    Inflammation research 25 (1988), S. 225-227 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The peripheral and central terminals of primary afferents of the cat's knee joint were studied with light- and electron microscopy (including HRP-transprot methods). The majority of these afferent fibres are unmyelinated or thinly myelinated. In the periphery, they terminate in non-corpuscular endings. A dense network of branching nerve fibres surround the blood vessels to terminate at the vessel walls or in the adjacent dense collagenous tissue. Besides the terminals the fibres show preterminal bulges which are assumed to represent additional transduction sites. This implies that the whole distal fibre portion has a receptive function. The spinal projection is located in lamina I and V–VII of the dorsal horn. This location parallels that of muscular and visceral fibres, pointing to the possibility of a common projection pattern for deep somatic afferent fibres in the spinal cord of the cat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01965018
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  • 3
    Electronic Resource
    Electronic Resource
    The effects of phorbol ester on slowly conducting afferents of the cat's knee joint (1993)
    Springer
    Experimental brain research 92 (1993), S. 391-398 
    Details
    ISSN: 1432-1106
    Keywords: Joint afferents ; Nociception ; Transduction ; Phorbol esters ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of β -phorbol 12, 13-dibutyrate (PDBu) on the discharge properties of slowly conducting knee joint afferents (group III and group IV fibers) were studied to determine the role of protein kinase C in nociception. Extracellular single unit recordings were made from small filaments dissected from the medial articular nerve in cats anesthetized with alphachloralose. PDBu was applied intra-arterially close to the joint in concentrations of 10-6 up to 10-4 M. The afferents were classified as low-threshold and high-threshold units with regard to their sensitivity to passive noxious and innocuous movements of the knee joint. Following PDBu application, an excitation occurred in 28% of the group III and in 40% of the group IV fibers. An enhancement of responses to passive movements of the joint (sensitization) occurred in 37% of group III and 19% of group IV afferents. In summary, 37.5% of the low-threshold and 50% of the high-threshold fibers proved to be sensitive to PDBu. Most of the PDBu-positive units responded also to bradykinin, whereas only a few PDBu-positive units were sensitive to prostaglandin I2 and E2. We conclude from these results that, in a distinct population of slowly conducting joint afferents, protein kinase C is likely to be involved in the process of transduction. Thus, pain and hyperalgesia may be mediated at least partly by intracellular mechanisms that are linked to protein kinase C.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229027
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  • 4
    Electronic Resource
    Electronic Resource
    Aktivierung trigeminaler Hirnstammneurone durch chemische Stimulation der Dura mater encephali (1997)
    Springer
    Der Schmerz 11 (1997), S. 322-327 
    Details
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Kopfschmerz ; Trigeminale Nozizeption ; Dura mater ; Chemonozizeption ; Key words Headache ; Trigeminal nociception ; Dura mater ; Chemonociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Introduction: Headache is thought to be generated by nociceptive processes within the meninges, followed by activation of trigeminal neurons within the brainstem. The noxious stimuli initially involved in these nociceptive processes are unknown. A preparation was developed in the barbiturate-anesthetized rat, in which the activation of trigeminal brain stem neurons by selective local stimulation of the dura mater could be observed. Methods: The dura mater encephali was exposed by trepanizing the parietal bone up to the sagittal superior sinus. The surface of the dura was stimulated with electrical pulses using bipolar electrodes. Extracellular recordings were made from neurons in the subnucleus interpolaris and caudalis of the spinal trigeminal nucleus. Neurons driven by meningeal afferents were identified by electrical stimulation and by probing their receptive fields on the dura mater. For chemical stimulation a combination of several inflammatory mediators (bradykinin, serotonin, histamine and prostaglandin E2, each 10−4 M, pH 6.1) was topically applied to the dura mater or injected through a catheter into the sagittal sinus. Results: Most of the trigeminal brain stem neurons with input from the parietal dura mater had convergent input from the facial skin with preponderance of the periorbital region. A high proportion of neurons (69%) could be activated by the combination of inflammatory mediators administered to the dura mater. Conclusion: We conclude that chemical stimuli activating the meningeal nociceptive system may play a decisive role in the generation of headache. This is particularly relevant for the nociceptive processes during neurogenic inflammation, which is believed to be an important step in the pathophysiology and development of migraine pain. The preparation presented here may be a valuable model for further studying the neurophysiological changes that are involved in the generation of headache.
    Notes: Zusammenfassung Als Modell zum Studium der nozizeptiven Vorgänge, die von den Hirnhäuten ausgehen und beim Menschen für die Entstehung von Kopfschmerzen verantwortlich gemacht werden, wurde eine Präparation entwickelt, bei der die Aktivität trigeminaler Hirnstammneurone unter mechanischer und chemischer Stimulation der freigelegten parietalen Dura mater encephali bei Ratten in Barbituratnarkose registriert werden kann. Extrazelluläre Ableitungen wurden von 36 Neuronen im Subnucleus interpolaris/caudalis des trigeminalen Hirnstammkernes vorgenommen. Diese Neurone hatten rezeptive Felder, die entlang der A. meningea media und des Sinus sagittalis superior angeordnet waren. Alle diese Neurone wiesen zusätzlich kutane rezeptive Felder im Gesichtsbereich auf, die besonders häufig periorbital und frontal lokalisiert waren. Die Mehrzahl (69%) der trigeminalen Hirnstammzellen ließ sich durch eine Mischung aus verschiedenen Entzündungsmediatoren (Bradykinin, Serotonin, Histamin, Prostaglandin E2, alle in einer Konzentration von 10−4 M) mit einem pH von 6,1 aktivieren, wenn diese topisch auf die freigelegte Dura mater appliziert wurde. Die Injektion der Mischung in den Sinus sagittalis superior erregte die Hälfte der Neurone, die in der Nähe des Sinus ein rezeptives Feld aufwiesen. Die Ergebnisse werden im Hinblick auf die Verteilung der rezeptiven Felder, die wirksamen Stimuli und deren mögliche Relevanz für die meningeale Nozizeption und die Kopfschmerzentstehung diskutiert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004820050104
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  • 5
    Electronic Resource
    Electronic Resource
    Was ist ein Nozizeptor? (1997)
    Springer
    Der Schmerz 11 (1997), S. 353-366 
    Details
    ISSN: 1432-2129
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Viele Nozizeptoren können durch noxische Reize, insbesondere durch Hitze sowie irritierende und inflammatorische Substanzen (z.B. Bradykinin, Prostaglandin I2, NO, Leukotriene, TNF, Interleukine usw.) sensibilisiert werden. Dies führt zur Schwellenerniedrigung des Rezeptors und häufig zu einer Vergrößerung des rezeptiven Felds. Antidrome elektrische Stimulation von nozizeptiven Afferenzen ruft Entzündungszeichen wie Vasodilatation und Extravasation von Blutplasma hervor. Mediatoren dieser neurogenen Entzündung sind die Neuropeptide Substanz P, Neurokinin A und CGRP. Mit dem Ziel einer peripher wirkenden Pharmakotherapie von Schmerzen wird experimentell und klinisch versucht, die Aktivität des nozizeptiven Systems auf der Ebene der Nozizeptoren zu hemmen. Zu den direkt oder indirekt am Nozizeptor wirkenden Substanzen gehören steroidale und nicht-steroidale Analgetika, Capsaicin-Analoga, Bradykinin-Antagonisten, Opioide und (im trigeminalen System) 5-HT1-Agonisten.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004820050110
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    Paper (German National Licenses)
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