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  • 1
    ISSN: 1432-1106
    Keywords: Joint ; Pain ; Inflammation ; Spinal cord ; Ascending tracts ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Recordings were made from 16 ascending tract cells in the spinal cords of anaesthetized, spinalized cats before and after an acute arthritis was produced by injection of kaolin and carrageenan into the knee joint. 2. The responses tested routinely were to passive flexion of the knee, an innocuous movement. In some cases, responses to other movements were also tested, and changes in background discharge rates were monitored. 3. Control recordings for a period of 1 h or in 3 cases of 3 h indicated that the responses to flexion were reasonably stationary. 4. Four tract cells that initially showed little or no response to flexion of the knee joint developed large responses within 1 to 2 h after inflammation of the joint. 5. Another 9 cells were tested that had responses to flexion of the knee joint prior to inflammation. In 6 cases, inflammation produced enhanced static or transient responses. In 2 cases, the effect of flexion was initially inhibitory or variable, but after inflammation these cells showed large excitatory responses. In the other case, inflammation had no effect. Background discharges were increased by inflammation in 6 of these 9 cells. 6. The effect of inflammation of the knee joint was tested on 3 tract cells that had no clearly defined receptive field in the knee. In 1 case, a response developed to knee flexion after acute inflammation was produced. In the other 2 cases, there were initially responses to knee flexion, but these were unchanged by inflammation. 7. Two of the cells tested had bilateral receptive fields in or around the knee joints. Inflammation of one knee joint enhanced the responses to flexion of the same but not of the contralateral knee in one case but greatly increased the responses to flexion of both knees in the other case. 8. Injections of prostaglandin (PGE2) caused an enhancement of the responses to knee flexion beyond that caused by inflammation in 5 of 7 cases. One cell whose responses to flexion of the knee were unaffected by inflammation showed inhibitory responses to prostaglandin injections into the inflamed knee joint. 9. The effects of inflammation on the responses of ascending tract cells of the spinal cord appear to serve as a useful neural model of the events responsible for the development of arthritic pain.
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  • 2
    ISSN: 1432-1106
    Keywords: Joint ; Spinal cord ; Pain ; Ascending tracts ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (“s” cells), 17 neurones excited by receptors in deep tissues (“d” cells), 15 units with a convergent input from receptors in skin and deep tissues (“sd” cells), and 25 neurones with a convergent input from the knee joint and either skin (“sj” cells), deep tissues (“dj” cells) or both (“sdj” cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. “S” and “sj” cells were found almost exclusively in the dorsal horn, whereas many “d”, “sd”, “sdj” and “dj” units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (“sj” cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (“sdj” cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 “dj” cells, the receptive fields included not only the knee joint but also deep fields like those of “sdj” cells. 6. Cutaneous receptive fields were classified as “low threshold” (cells excited best by innocuous intensities of mechanical stimulation), “wide dynamic range” (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.
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  • 3
    ISSN: 1432-1106
    Keywords: Key words N-type calcium channel ; Mustard oil ; Central sensitization ; Nociception ; Pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Administration of the N-type calcium channel antagonist ω-conotoxin GVIA to the spinal cord reduces spinal neuronal responses to innocuous and noxious pressure applied to the knee, both in rats with normal knees and in rats in which a knee inflammation has induced a state of hyperexcitability in spinal neurons (Neugebauer et al. 1996, J Neurophysiol 76: 3740–3749). In the present experiments we studied whether the development of hyperexcitability of spinal neurons induced by intra-articular injection of mustard oil, an excitant of C-fibres, can be influenced by spinal pretreatment with ω-conotoxin GVIA. In anaesthetized rats, responses of wide-dynamic-range neurons were recorded in the spinal dorsal horn when standardized stimulation with innocuous and noxious pressure was applied to the knee and ankle joints. Injection of mustard oil into the knee joint cavity caused an initial neuronal discharge followed by an early (peaking at about 15 min) and a late (after 60 min) facilitation of responses to innocuous and noxious stimulation of the knee. Responses to ankle stimulation showed only the late facilitation. When ω-conotoxin GVIA (20 μl, 1 μM) was applied into a small trough onto the spinal cord above the recording site the responses to articular stimulation were reduced. Furthermore, when mustard oil was injected while ω-conotoxin GVIA was on the spinal cord, the early increase in the neuronal responses to innocuous pressure on the knee and the late increase in responses to noxious pressure on the ankle were significantly smaller than those observed in rats not treated with ω-conotoxin GVIA; the drop in the responses to noxious pressure on the knee was not significant. Thus the spinal application of ω-conotoxin GVIA reduced but did not completely prevent the fast and slow development of neuronal hyperexcitability of spinal cord neurons produced by a prompt and strong excitation of afferent C-fibres. This suggests that N-type calcium channels are important for the development of spinal cord hyperexcitability.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 72 (1988), S. 219-224 
    ISSN: 1432-1106
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 5
    ISSN: 1432-1106
    Keywords: [K+]0 Spinal cord ; Posterior articular nerve ; Knee joint ; Inflammation ; Pain ; Arthritis ; Nociception ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 20 cats anaesthetized with alpha-chloralose and spinalized at the thoracolumbar junction we investigated the role of stimulation induced accumulation of extracellular potassium in the spinal cord in the processing of nociceptive discharges from the knee joint. For that we electrically stimulated the posterior articular nerve of the knee. We further performed innocuous and noxious stimulation of the knee and of other parts of the leg and studied the effect of an acute inflammation of the knee on [K+]0 in the spinal cord. Innocuous stimulation of the skin (brushing or touching) and innocuous movements in the knee joint all induced rises in [K+]0 which were maximal at recording depths of 1500 to 2200 μm below the surface of the cord dorsum. Peak increases were 0.4 mM for touching the leg and 1.7 mM during rhythmic flexion/ extension of the knee joint. Noxious stimulation of the skin, the paw, the tendon and noxious movements of the knee joint also produced rises in [K+]0, which were somewhat larger for the individual types of stimuli than those produced by innocuous intensities. Electrical stimulation of the posterior articular nerve induced rises in [K+]0 by up to 0.6 mM. Stimulus intensities sufficient to activate unmyelinated group IV fibers were only slightly effective in raising [K+]0 above the levels reached during stimulation of myelinated group II and III fibers. During development of an acute inflammation of the knee joint (induced by kaolin and carrageenan), increases in [K+]0 and associated field potentials became larger by about 25%. We assume that this reflects an increase in neuronal responses. In conclusion, changes in [K+]0 in the spinal cord are some-what larger during noxious stimulation than during innocuous stimulation. The absolute level reached depended more on the site and type of stimulation than on the actual stimulus intensity itself. Hence a critical role of spinal K+ accumulation for nociception is unlikely.
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  • 6
    ISSN: 1432-1106
    Keywords: Pain ; Inflammation ; Descending inhibition ; Nociception ; Spinal cord ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In ten cats, single unit electrical activity was recorded in the lumbosacral spinal cord from neurones driven by stimulation of afferent fibres from the ipsilateral knee joint. Tonic descending inhibition (TDI) on the responses of these cells was measured as increases in resting and evoked activity of the neurones following reversible spinalization of the animals with a cold block at upper lumbar level. Acute inflammation of the knee joint was induced in five of the cats by the injection of kaolin and carrageenan into the joint. TDI was observed in 25 of 33 neurones recorded in normal animals (76%) and in 36 of 40 (90%) neurones recorded in animals with acute knee joint inflammation. In both kinds of preparation TDI was more pronounced in neurones recorded in the deep dorsal horn and in the ventral horn than in those recorded in the superficial dorsal horn. There was a tendency in the whole sample for TDI to be greater in neurones with input from inflamed knees. We conclude that the spinal processing of afferent information from joints is under tonic descending influences and that the amount of TDI can be altered during acute arthritis.
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  • 7
    ISSN: 1432-1106
    Keywords: Spinal cord ; Arthritis ; Nociception ; Joint ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to determine the discharge and receptive field properties of spinal cord neurons with ankle input in spinal segments L4-6 in the rat, both under control conditions and during the course of an adjuvant-induced unilateral inflammation in the ankle. The extent of receptive fields in the skin and deep tissue was assessed using brush, pinch and compression stimuli. Neurons were categorized as nociceptive-specific or wide-dynamic-range neurons on the basis of their response thresholds and responses to suprathreshold stimuli. At all stages of inflammation (2, 6, 13 and 20 days post inoculation) the population of neurons with ankle input showed differences from the population of neurons with ankle input in control rats. There was a reduction in the number of neurons that appeared as nociceptive specific and a concomitant increase in the number of neurons showing a wide-dynamic-range response profile. The receptive fields of the neurons with ankle input were markedly larger in rats with inflammation in the ankle region and mainly spread proximally on the ipsilateral hindlimb and also to the abdomen and tail in some cases. There was also an increase in the number of neurons with contralateral excitatory inputs. The mechanical thresholds at the ankle joint and proximal parts of the ipsilateral hindlimb were less in arthritic rats than in controls. The proportion of spontaneously active neurons was also increased in rats during the initial and later stages of inflammation, although there was no significant increase in the mean spontaneous discharge frequency. These data show that there are long-term changes in the receptive field and response properties of neurons in intact rats with chronic unilateral adjuvant-induced inflammation similar to those described previously in spinal cats with acute inflammation (Neugebauer and Schaible 1990). It is presumed that similar afferent and spinal mechanisms are at work under acute and chronic inflammatory conditions which produce hyperexcitability in spinal neurons with joint input.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Manuelle Medizin 35 (1997), S. 77-81 
    ISSN: 1433-0466
    Keywords: Key words Nociceptors • Sensitization • Joint pain • Neurogenic inflammation ; Schlüsselwörter Nozizeptoren • Sensibilisierung • Gelenkschmerz • neurogene Entzündung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Gelenke werden von nozizeptiven Nervenfasern (Nozizeptoren) innerviert, die ausschließlich bei Einwirkung gewebeschädigender Reize (Noxen) aktiviert werden. In der Regel führt die Erregung von Nozizeptoren beim wachen Menschen zu Schmerzen. Besonders bei entzündlichen Vorgängen werden die sensorischen Endigungen vieler Nozizeptoren im Gewebe sensibilisiert. Unter diesen Bedingungen genügen bereits normalerweise nichtnoxische bzw. nichtschmerzhafte Reize, um die Nozizeptoren zu aktivieren und Schmerzen auszulösen. Für die Sensibilisierung von Nozizeptoren ist die Wirkung von Entzündungsmediatoren wie Bradykinin und Prostaglandine wichtig. Neben ihrer sensorischen Funktion besitzen viele Nozizeptoren auch eine efferente Funktion. Durch die Freisetzung von Neuropeptiden wie Substanz P und Calcitonin-gene-related-Peptide im Gewebe bewirken sie eine neurogene Entzündung. Diese efferente Wirkung der Nozizeptoren trägt zur Entstehung entzündlicher Gewebeveränderungen bei.
    Notes: Abstract Joints are innervated by nociceptive nerve fibres (nociceptors), which are only activated by tissue-damaging stimuli. This activation causes pain in conscious humans. The sensory terminals of many nociceptors in the tissue are sensitized by inflammatory processes. Under these conditions, normally innocuous and non-painful stimuli are sufficient to activate nociceptors and to elicit pain. The effect of inflammatory mediators such as bradykinin and prostaglandins is important for the process of sensitization. In addition to their sensory function, many nociceptors have an efferent function. They evoke a neurogenic inflammation by the release of neuropeptides such as substance P and calcitonin gene-related peptide into the tissue. The efferent function of nociceptors contributes to the generation of inflammatory lesions of the tissue.
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  • 9
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In cats the injections of kaolin and carrageenan into the knee joint lead to an acute arthritis which develops within 1–3 hours. In parallel articular afferents (low, high threshold and unresponsive ones) are becoming (more) sensitive to movements in the working range of the joint and many show (enhanced) ongoing discharges. Consequently spinal nociceptive-specific and wide dynamic range neurons with afferent input from the inflamed knee develop (increased) responsiveness to gentle stimulation of the joint. But in addition most of these neurons display enhanced reactions to non-inflamed parts of their receptive fields, too, and some neurons show enlargement of their total receptive fields. These latter findings indicate that the sensitization of spinal neurons is not simply reflecting the increased afferent input from the inflamed knee but that intrinsic spinal mechanisms may participate in the sensitization process.
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  • 10
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In spinal cord neurons in anesthetized rats, the role of neurokinin A and neurokinin-2 receptors in the processing of nociceptive information from the knee joint was studied. The specific non-peptide antagonist at the neurokinin-2 receptor, SR48968, its inactive R-enantiomer, SR48965, neurokinin A, substance P and (R, S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), were administered ionophoretically close to neurons with input from the knee joint. SR48968 reduced the effects of exogenous neurokinin A, but not those of exogenous substance P and AMPA, indicating selective blockade of neurokinin-2 receptors. In most neurons with input from the normal knee joint, SR48968 reduced dose-dependently the responses to noxious pressure applied to the knee, and in ˜50% of the neurons the responses to innocuous pressure. The administration of SR48968 during the induction of an experimental joint inflammation markedly attenuated the development of inflammation-evoked hyperexcitability. In hyperexcitable neurons with input from the inflamed joint, SR48968 reduced the responses to noxious and innocuous pressure. The relative reduction of the responses was more pronounced than in neurons with input from the normal joint. None of the effects of SR48968 was mimicked by SR48965. These data show that neurokinin-2 receptors are involved in the spinal processing of nociceptive information from the normal joint. Furthermore, neurokinin-2 receptors must be coactivated at an early stage of inflammation, to allow the generation of hyperexcitability. Finally, neurokinin-2 receptors are involved in the maintenance of hyperexcitability during inflammation. In summary, spinal neurokinin-2 receptors are important in the generation of pain in the normal and inflamed joint.
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