| 1. |
- Nilsson, H-J., et al.
(författare)
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Profound inhibition of chronic itch induced by stimulation of thin cutaneous nerve fibres
- 2004
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Elsevier. - 0926-9959 .- 1468-3083. ; 18:1, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the fact that severe itch is common in many dermatological diseases, the therapeutic arsenal against itching is limited. From neurophysiological experiments, using a new technique termed cutaneous field stimulation, it is known that acute itch can be effectively relieved by stimulation of cutaneous nociceptors. METHODS: We tested the effects of cutaneous field stimulation (25 min, 16 electrodes, 4 Hz per electrode, up to 0.8 mA) on chronic itch due to atopic dermatitis. Transcutaneous electrical nerve stimulation (100 Hz, up to 26 mA) was used for comparison. In 27 patients, itch was measured just prior to, during and at regular intervals up to 12 h after either type of treatment. RESULTS: Both treatments augmented the itch sensation during ongoing stimulation, presumably reflecting an altered sensory processing in the somatosensory pathways of chronic itch patients. However, after cessation of cutaneous field stimulation, but not transcutaneous electrical nerve stimulation, the itch sensation was significantly depressed for up to 7 h. The peak inhibitory effect (about 25% of control) was reached between 1 and 5 h poststimulation. Neither treatment had any significant effect on alloknesis, as measured before and 10 min after stimulation. CONCLUSION: It is concluded that cutaneous field stimulation strongly depresses chronic itch, and is a potentially useful symptomatic treatment of itch.
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| 2. |
- Garwicz, Martin, et al.
(författare)
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Common principles of sensory encoding in spinal reflex modules and cerebellar climbing fibres.
- 2002
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Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 540:Pt 3, s. 1061-1069
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Tidskriftsartikel (refereegranskat)abstract
- An important step towards understanding the function of olivo-cerebellar climbing fibres must be to clarify what they signal. We suggest that climbing fibres projecting to paravermal cerebellum mediate highly integrated sensorimotor information derived from activity in spinal withdrawal reflex modules acting on single forelimb muscles. To test this hypothesis, cutaneous nociceptive receptive fields of spinal reflex modules were mapped and compared to those of climbing fibres. Quantitative methods were used both for mapping and for comparing receptive fields. The organization of muscle afferent input converging on individual climbing fibres was analysed in the light of results from receptive field comparisons. Individual cutaneous receptive fields in the two systems were readily matched. Matched pairs were highly similar with regard to detailed distributions of sensitivity: correlation coefficient r = 0.85; overlap of receptive field foci 72 % (average values). The olivary targets of muscle afferents from a given muscle were mainly climbing fibres with cutaneous receptive fields similar to that of the muscle itself, but to a lesser extent also other climbing fibres. In conclusion, paravermal climbing fibres apparently convey information integrating (i) cutaneous input to an individual spinal withdrawal reflex module, (ii) muscle afferent input from the output muscle of that module and (iii) muscle afferent input from muscles that constitute the output of functionally related modules. This suggests that an individual climbing fibre signals cutaneous sensory events reflecting activity of a single muscle conditional upon the functional state of the muscle itself and that of functionally related muscles.
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| 3. |
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| 4. |
- Kalliomäki, Jarkko, et al.
(författare)
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Spinal NMDA-receptor dependent amplification of nociceptive transmission to rat primary somatosensory cortex (SI).
- 2003
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Ingår i: Pain. - 1872-6623. ; 104:1-2, s. 195-200
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Tidskriftsartikel (refereegranskat)abstract
- The role of NMDA mechanisms in spinal pathways mediating acute nociceptive input to the somatosensory cortex is not clear. In this study, the effect of NMDA-antagonists on nociceptive C fibre transmission to the primary somatosensory cortex (SI) was investigated. Cortical field potentials evoked by CO2-laser stimulation of the skin were recorded in the halothane/nitrous oxide anaesthetized rat. The SI nociceptive evoked potential (EP) amplitudes were dependent on the frequency of noxious heat stimulation. The amplitudes of SI potentials evoked by CO2-laser pulses (duration 15–20 ms, stimulation energy 21–28 mJ/mm2) delivered at a frequency of 0.1 Hz were approximately 40% of the amplitudes of potentials evoked by 1.0 Hz stimulation. After intrathecal lumbar application of either of the NMDA-antagonists CPP or MK-801, the amplitudes of nociceptive SI potentials, evoked by 1.0 Hz stimulation of the contralateral hindpaw, were reduced to approximately 40% of controls. By contrast, field potentials evoked by 0.1 Hz stimulation of the hindpaw were unaffected by MK-801. SI potentials evoked by 1.0 Hz stimulation of the contralateral forepaw did not change after lumbar application of CPP or MK-801, indicating that the depression of hindpaw EPs was due to a segmental effect in the spinal cord. It is concluded that spinal NMDA-receptor mechanisms amplify the acute transmission of nociceptive C fiber input to SI in a frequency-dependent way.
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| 5. |
- Levinsson, Anders, et al.
(författare)
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Functional connections are established in the deafferented rat spinal cord by peripherally transplanted human embryonic sensory neurons
- 2000
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 12:10, s. 3589-3595
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Tidskriftsartikel (refereegranskat)abstract
- Functionally useful repair of the mature spinal cord following injury requires axon growth and the re-establishment of specific synaptic connections. We have shown previously that axons from peripherally grafted human embryonic dorsal root ganglion cells grow for long distances in adult host rat dorsal roots, traverse the interface between the peripheral and central nervous system, and enter the spinal cord to arborize in the dorsal horn. Here we show that these transplants mediate synaptic activity in the host spinal cord. Dorsal root ganglia from human embryonic donors were transplanted in place of native adult rat ganglia. Two to three months after transplantation the recipient rats were examined anatomically and physiologically. Human fibres labelled with a human-specific axon marker were distributed in superficial as well as deep laminae of the recipient rat spinal cord. About 36% of the grafted neurons were double labelled following injections of the fluorescent tracers MiniRuby into the sciatic and Fluoro-Gold into the lower lumbar spinal cord, indicating that some of the grafted neurons had grown processes into the spinal cord as well as towards the denervated peripheral targets. Electrophysiological recordings demonstrated that the transplanted human dorsal roots conducted impulses that evoked postsynaptic activity in dorsal horn neurons and polysynaptic reflexes in ipsilateral ventral roots. The time course of the synaptic activation indicated that the human fibres were non-myelinated or thinly myelinated. Our findings show that growing human sensory nerve fibres which enter the adult deafferentated rat spinal cord become anatomically and physiologically integrated into functional spinal circuits.
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| 6. |
- Levinsson, Anders, et al.
(författare)
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Spinal sensorimotor transformation: Relation between cutaneous somatotopy and a reflex network
- 2002
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 22:18, s. 8170-8182
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Tidskriftsartikel (refereegranskat)abstract
- The projection of primary afferents onto spinal interneurons constitutes the first step in sensorimotor transformations performed by spinal reflex systems. Despite extensive studies on spinal somatotopy, uncertainties remain concerning the extent and significance of representational overlap and relation to spinal reflex circuits. To address these issues, the cutaneous projection from the hindpaw and its relation to the topography of lamina V neurons encoding withdrawal reflex strength ("reflex encoders") was studied in rats. Thin and coarse primary afferent terminations in laminas II and III-IV, respectively, were mapped by wheat germ agglutinin-horseradish peroxidase and choleragenoid tracing. The functional weights of these projections were characterized by mapping nociceptive and tactile field potentials and compared with the topography of reflex encoders. Both anatomical and physiological data indicate that thin and coarse skin afferent input is spatially congruent in the horizontal plane. The representation of the hindpaw in the spinal cord was found to be intricate, with a high degree of convergence between the projections from different skin sites. "Somatotopic disruptions" such as the representation of central pads medial to that of the digits were common. The weight distribution of the cutaneous convergence patterns in laminas III-IV was similar to that of lamina V reflex encoders. This suggests that the cutaneous convergence and features such as somatotopic disruptions have specific relations to the sensorimotor transformations performed by reflex interneurons in the deep dorsal horn. Hence, the spinal somatotopic map may be better understood in light of the topography of such reflex systems.
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| 7. |
- Nilsson, Hans Jörgen, et al.
(författare)
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Long term depression of human nociceptive skin senses induced by thin fibre stimulation.
- 2003
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Ingår i: European Journal of Pain. - 1090-3801. ; 7:3, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- We have recently shown that stimulation, through a multi-electrode array, of thin nerve fibres close to the dermo-epidermal junction in the skin, produces powerful inhibition of itch and, to a lesser degree, cutaneous pain in humans. Here, we have studied the induction time and frequency dependency (range 1–10 Hz) of the inhibitory effects of such stimulation on itch, mechanical, and thermal pain, in 20 healthy subjects. Sixteen electrodes applied on the skin were consecutively stimulated using a method termed cutaneous field stimulation (CFS). The results show that different treatment periods with CFS were required for the induction of significant inhibitory effects on different nociceptive qualities: 1st heat pain (1 min), itch (3 min), 2nd heat pain (6 min), pinch evoked pain (8 min). Six to ten minutes stimulation sufficed to induce peak inhibitory effects on all these sensory qualities while longer stimulation (up to 40 min) did not cause significantly stronger inhibition. The effects on itch, 1st and 2nd heat pain lasted over 55 min after termination of CFS. There was no effect on prickle. No significant difference in inhibitory effects of different stimulation frequencies (1, 4 and 10 Hz/electrode) was found. The induction time and effective stimulation frequencies may suggest that the underlying mechanisms are similar to those of long term depression (LTD) previously described in the spinal cord in animal experiments.
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| 8. |
- Nilsson, H-J, et al.
(författare)
-
Profound inhibition of chronic itch induced by stimulation of thin cutaneous nerve fibres.
- 2004
-
Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 1468-3083 .- 0926-9959. ; 18:1, s. 37-43
-
Tidskriftsartikel (refereegranskat)abstract
- Background Despite the fact that severe itch is common in many dermatological diseases, the therapeutic arsenal against itching is limited. From neurophysiological experiments, using a new technique termed cutaneous field stimulation, it is known that acute itch can be effectively relieved by stimulation of cutaneous nociceptors. Methods We tested the effects of cutaneous field stimulation (25 min, 16 electrodes, 4 Hz per electrode, up to 0.8 mA) on chronic itch due to atopic dermatitis. Transcutaneous electrical nerve stimulation (100 Hz, up to 26 mA) was used for comparison. In 27 patients, itch was measured just prior to, during and at regular intervals up to 12 h after either type of treatment. Results Both treatments augmented the itch sensation during ongoing stimulation, presumably reflecting an altered sensory processing in the somatosensory pathways of chronic itch patients. However, after cessation of cutaneous field stimulation, but not transcutaneous electrical nerve stimulation, the itch sensation was significantly depressed for up to 7 h. The peak inhibitory effect (about 25% of control) was reached between 1 and 5 h poststimulation. Neither treatment had any significant effect on alloknesis, as measured before and 10 min after stimulation. Conclusion It is concluded that cutaneous field stimulation strongly depresses chronic itch, and is a potentially useful symptomatic treatment of itch.
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| 9. |
- Petersson, Per, et al.
(författare)
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An imaging system for monitoring receptive field dynamics
- 2001
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Ingår i: Journal of Neuroscience Methods. - 1872-678X. ; 104:2, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- The paper describes a computerized method, termed receptive field imaging (RFI), for the rapid mapping of multiple receptive fields and their respective sensitivity distributions. RFI uses random stimulation of multiple sites, in combination with an averaging procedure, to extract the relative contribution from each of the stimulated sites. Automated multi-electrode stimulation and recording, with spike detection and counting, are performed on-line by the RFI programme. Direct user interpretation of receptive field changes is made possible by a user-friendly graphic interface. A series of imaging experiments was carried out to evaluate the functional capacity of the system. RFI was tested on the receptive fields in the nociceptive withdrawal reflex (NWR) system in the rat. RFI replicates the results obtained with conventional methods and allows the display of receptive field dynamics induced by topical spinal cord application of morphine and naloxone on a minute-to-minute time scale. Data variance was estimated, and proved to be small enough to yield a stable representation of the receptive field, thereby achieving a high sensitivity in dynamic imaging experiments. The large number of stimulation and registration sites that can be monitored in parallel permits detailed network analysis of synaptic sets, corresponding to 'connection weights' between individual neurones.
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| 10. |
- Petersson, Per, et al.
(författare)
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Properties of an adult spinal sensorimotor circuit shaped through early postnatal experience.
- 2004
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 92:1, s. 280-288
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Tidskriftsartikel (refereegranskat)abstract
- During development, information about the three-dimensional shape and mechanical properties of the body is laid down in the synaptic connectivity of sensorimotor systems through adaptive mechanisms. This functional adaptation occurs through alteration of connection properties. Here, we characterize the differences between strong and weak connections in the nociceptive withdrawal reflex in adult decerebrate spinal rats, representing the preserved end product of the developmental adaptation process. Stronger excitatory reflex connections from the skin onto a muscle had relatively higher gain in their input-output relations, shorter onset latencies ( up to similar to 150 ms) and lower trial-to-trial variability in relation to response amplitude (SD similar to mean(1/2)) than weaker pathways. Although inhibitory and excitatory nociceptive receptive fields of a muscle overlap to some degree, the results indicate that the inhibitory input is not a major determinant of the gain distribution within the excitatory receptive field and vice versa. The N-methyl-D-aspartate ( NMDA) receptor antagonist, D-2-amino-5-phosphonovalerate (0.1 - 1 mug), applied topically on the spinal cord reduced the gain, whereas the response amplitude was mainly reduced by an absolute number by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor antagonist, 6-nitro-7-sulfamoylbenzo(f) quinoxaline-2,3- dione ( 1 - 10 mug). The results indicate that NMDA receptors have a critical role in gain regulation in the nociceptive withdrawal reflex system. It is suggested that after normal postnatal experience-dependent adaptation, the number of connections from a given skin site onto the reflex encoding interneurons is a major determinant of the difference in gain.
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