| 1. |
- Nilsson, H-J., et al.
(author)
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Profound inhibition of chronic itch induced by stimulation of thin cutaneous nerve fibres
- 2004
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In: Journal of the European Academy of Dermatology and Venereology. - : Elsevier. - 0926-9959 .- 1468-3083. ; 18:1, s. 37-43
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Journal article (peer-reviewed)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. |
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| 3. |
- Ljungquist, B, et al.
(author)
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Discrepancies between cortical and behavioural long-term readouts of hyperalgesia in awake freely moving rats
- 2016
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In: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 20:10, s. 1689-1699
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is still unclear to what extent the most common animal models of pain and analgesia, based on indirect measures such as nocifensive behaviours, provide valid measures of pain perception.METHODS: To address this issue, we developed a novel animal model comprising a more direct readout via chronically (>1 month) implanted multichannel electrodes (MCE) in rat primary somatosensory cortex (S1; known to be involved in pain perception in humans) and compared this readout to commonly used behavioural pain-related measures during development of hyperalgesia. A translational method to induce hyperalgesia, UVB irradiation of the skin, was used. Localized CO2 laser stimulation was made of twenty skin sites (20 stimulations/site/observation day) on the plantar hind paw, before and during the time period when enhanced pain perception is reported in humans after UVB irradiation.RESULTS: We demonstrate a 2-10 fold significant enhancement of cortical activity evoked from both irradiated and adjacent skin and a time course that corresponds to previously reported enhancement of pain magnitude during development of primary and secondary hyperalgesia in humans. In contrast, withdrawal reflexes were only significantly potentiated from the irradiated skin area and this potentiation was significantly delayed as compared to activity in S1.CONCLUSIONS: The present findings provide direct evidence that chronic recordings in S1 in awake animals can offer a powerful, and much sought for, translational model of the perception of pain magnitude during hyperalgesia. WHAT DOES THIS STUDY ADD?: In a novel animal model, chronic recordings of nociceptive activity in primary somatosensory cortex (S1) in awake freely moving rats are compared to behavioural readouts during UVB-induced hyperalgesia. Evoked activity in rat S1 replicates altered pain perception in humans during development of hyperalgesia, but withdrawal reflexes do not.
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| 4. |
- Biro, T, et al.
(author)
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How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches
- 2005
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In: Experimental Dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 14:3, s. 225-225
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Journal article (peer-reviewed)abstract
- While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.
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| 5. |
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| 6. |
- Holmkvist, Alexander Dontsios, et al.
(author)
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Local delivery of minocycline-loaded PLGA nanoparticles from gelatin-coated neural implants attenuates acute brain tissue responses in mice
- 2020
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In: Journal of Nanobiotechnology. - : Springer Science and Business Media LLC. - 1477-3155. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: Neural interfaces often elicit inflammatory responses and neuronal loss in the surrounding tissue which adversely affect the function and longevity of the implanted device. Minocycline, an anti-inflammatory pharmaceutics with neuroprotective properties, may be used for reducing the acute brain tissue responses after implantation. However, conventional administration routes require high doses which can cause adverse systemic side effects. Therefore, the aim of this study was to develop and evaluate a new drug-delivery-system for local and sustained administration of minocycline in the brain. Methods: Stainless steel needles insulated with Parylene-C were dip-coated with non-crosslinked gelatin and minocycline-loaded PLGA nanoparticles (MC-NPs) were incorporated into the gelatin-coatings by an absorption method and subsequently trapped by drying the gelatin. Parylene-C insulated needles coated only with gelatin were used as controls. The expression of markers for activated microglia (CD68), all microglia (CX3CR1-GFP), reactive astrocytes (GFAP), neurons (NeuN) and all cell nuclei (DAPI) surrounding the implantation sites were quantified at 3 and 7 days after implantation in mice. Results: MC-NPs were successfully incorporated into gelatin-coatings of neural implants by an absorption method suitable for thermosensitive drug-loads. Immunohistochemical analysis of the in vivo brain tissue responses, showed that MC-NPs significantly attenuate the activation of microglial cells without effecting the overall population of microglial cells around the implantation sites. A delayed but significant reduction of the astrocytic response was also found in comparison to control implants. No effect on neurons or total cell count was found which may suggest that the MC-NPs are non-toxic to the central nervous system. Conclusions: A novel drug-nanoparticle-delivery-system was developed for neural interfaces and thermosensitive drug-loads. The local delivery of MC-NPs was shown to attenuate the acute brain tissue responses nearby an implant and therefore may be useful for improving biocompatibility of implanted neuro-electronic interfaces. The developed drug-delivery-system may potentially also be used for other pharmaceutics to provide highly localized and therefore more specific effects as compared to systemic administration.
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| 7. |
- Kalliomäki, J, et al.
(author)
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Differential effects of a distant noxious stimulus on hindlimb nociceptive withdrawal reflexes in the rat.
- 1992
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In: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 4:7, s. 648-652
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Journal article (peer-reviewed)abstract
- Recent studies indicate that the nociceptive withdrawal reflexes to individual muscles are evoked by separate reflex pathways. The present study examines whether nociceptive withdrawal reflexes to different muscles are subject to differential supraspinal control in rats. A distant noxious stimulus was used to activate a bulbospinal system which selectively inhibits ‘multireceptive’ neurons (i.e. neurons receiving excitatory tactile and nociceptive inputs) in the dorsal horn of the spinal cord. Withdrawal reflexes, recorded with electromyographic techniques in single hindlimb muscles, were evoked by standardized noxious pinch. Thirty‐seven rats, anaesthetized with halothane and nitrous oxide, were used. Whereas withdrawal reflexes to the extensor digitorum longus and brevis, tibialis anterior and biceps posterior muscles were strongly inhibited, reflexes to interossei muscles were potentiated during noxious pinch of the nose. Reflexes to peronei muscles were not significantly changed. The effects on the reflexes usually had an onset latency of <0.5 s and outlasted the conditioning stimulation by up to 2 s. The monosynaptic la reflex to the deep peroneal nerve, innervating dorsiflexors of the digits and ankle, was not significantly changed during noxious pinch of the nose. Hence, the inhibitory effects on the hindlimb withdrawal reflexes induced by the conditioning stimulation were presumably exerted on reflex interneurons. It is concluded that nociceptive withdrawal reflexes to different hindlimb muscles are differentially controlled by descending pathways activated by a distant noxious stimulus. The results support our previous conclusion that there are separate nociceptive withdrawal reflex pathways to different hindlimb muscles.
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| 8. |
- Lee, Heui Chang, et al.
(author)
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Histological evaluation of flexible neural implants; Flexibility limit for reducing the tissue response?
- 2017
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In: Journal of Neural Engineering. - : IOP Publishing. - 1741-2560 .- 1741-2552. ; 14:3
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Journal article (peer-reviewed)abstract
- Objective. Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? Approach. Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (∼150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). Main results. We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. Significance. The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.
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| 9. |
- Ljungquist, Bengt, et al.
(author)
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A Bit-Encoding Based New Data Structure for Time and Memory Efficient Handling of Spike Times in an Electrophysiological Setup
- 2018
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In: Neuroinformatics. - : Springer. - 1539-2791 .- 1559-0089. ; 16:2, s. 217-229
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Journal article (peer-reviewed)abstract
- Recent neuroscientific and technical developments of brain machine interfaces have put increasing demands on neuroinformatic databases and data handling software, especially when managing data in real time from large numbers of neurons. Extrapolating these developments we here set out to construct a scalable software architecture that would enable near-future massive parallel recording, organization and analysis of neurophysiological data on a standard computer. To this end we combined, for the first time in the present context, bit-encoding of spike data with a specific communication format for real time transfer and storage of neuronal data, synchronized by a common time base across all unit sources. We demonstrate that our architecture can simultaneously handle data from more than one million neurons and provide, in real time (< 25 ms), feedback based on analysis of previously recorded data. In addition to managing recordings from very large numbers of neurons in real time, it also has the capacity to handle the extensive periods of recording time necessary in certain scientific and clinical applications. Furthermore, the bit-encoding proposed has the additional advantage of allowing an extremely fast analysis of spatiotemporal spike patterns in a large number of neurons. Thus, we conclude that this architecture is well suited to support current and near-future Brain Machine Interface requirements.
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