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S5-4 High-frequency oscillations in cortical myoclonus
S16 subjects. We concluded that the median nerve SEP amplitude changes are associated with motor disturbances in ALS. The cortical potential enhancement of SEPs with moderate weakness in ALS might reflect some compensatory function of the sensory cortex for motor disturbances. S5-4 High-frequency oscillations in cortical myoclonus M. Alegre1,2 1 Neurosciences Area, CIMA, University of Navarra, 2 Department of Neurology and Neurophysiology, Clinica Universidad de Navarra, Pamplona, Spain Patients with cortical myoclonus have motor cortex hyperexcitability, expressed neurophysiologically in the form of high-amplitude waves in the cortical components of the somatosensory-evoked potentials (giant SSEPs). We recently studied the HFOs in a group of 20 patients with cortical myoclonus of different origins, comparing the results obtained with the amplitude and latency of the classical SSEPs waves. Nine patients had no HFOs, and another nine patients had low-amplitude and/or delayed HFOs. The remaining two patients, the only without ataxia, had very high-amplitude HFOs with a long latency. These results suggest a heterogeneity in the pathophysiology of cortical myoclonus, and point toward a possible contribution of the cerebellum in the build-up of cortical high-frequency oscillations. On the other hand, the use of deep brain stimulation has allowed the direct recording of oscillatory activity from subcortical structures in human patients. During the last years, we have recorded high-frequency activity in the SSEPs in deep structures, like the VIM nucleus of the thalamus and the subthalamic nucleus, in several patients with deep brain stimulators implanted, including two subjects with cortical myoclonus. S6. Small fiber physiology S6-1 Physiology of low threshold unmyelinated sensory fibres J. Cole1 1 CoPMRE, University of Bournemouth and Poole Hospital, UK. Though it has been known since the 1930’s that mammals, including non-humanprimates, possess a system of cutaneous afferent c-fibres which respond optimally to gentle touch rather than nociception, their presence in humans has not been widely acknowledged, nor their function understood. Recently the properties of a novel class of mechanosensitive c-fibre afferent nerves (C-Tactile: CT), found in hairy skin, have been described. Microneurographic recordings from single afferent fibres innervating hairy skin in man first showed the presence of low threshold CT afferents in man. More recent studies, recording from single CT afferents from the forearm in man during controlled tactile stimulation across a unit’s receptive field, have shown an ‘inverted U’ response-function in spike discharge frequency, with a peak at stroke velocities of ~2 cm/sec. Psychophysical data, in which participants rate the affective intensity of the stimulus (like dislike), showed an identical affective response function; with the highest pleasantness ratings also at 2 3 cm/sec. Ab afferents tuning profiles and psychophysical ratings were very different. The cortical representationof CT’s has been determined, in the absence of Ab afferent input, by recording, with fMRI, from rare patients with a complete loss of large diameter myelinated afferents, but intact C-fibre systems (and a controlpopulation). Touch with a soft brush activates posterior insular cortex, andthe orbitofrontal cortex and may inhibit sensory cortex. In these patientspure CT stimulation may give rise to a diffuse, pleasant sensation, and may also evoke a sympathetic skin response. In addition to their role insignalling the pleasantness of cutaneous sensation, CT afferents may also have a role in affective or social touch and, speculatively, some disorders of this too. S6-2 Selective stimulation of cutaneous nociceptors by intra-epidermal electrical stimulation K. Inui1 1 Department of Integrative Physiology, National Institute for Physiological Sciences In studies of sensory systems, a well-controlled stimulus is required to activate the system being examined. An experimental stimulus should be quantifiable and reproducible (regularity and time distribution).
Oral Presentations: Symposia Additionally, for clinical application, safety, low cost, and simplicity of use are required. For the nociceptive system, the stimulation method that is fulfilling these requirements is limited. We have developed a method of intra-epidermal electrical stimulation (IES) for the selective activation of cutaneous A-delta fibers. For IES, a concentric bipolar needle electrode which consists of an outer ring 1.2 mm in diameter and inner needle that protrudes 0.1 mm from the outer ring is used. By pressing the electrode against the skin gently, the needle tip is inserted in the epidermis where nociceptors are located, while the outer ring is attached to the skin surface. A weak current passing through the electrode is expected to activate the superficial part of the skin selectively. We have been using this method to investigate the nociceptive system, and found that (1) IES with a very weak current (<0.3 mA) elicits a pricking sensation, (2) IES evoked potentials or magnetic fields that are similar to those evoked by laser stimulation, (3) the peripheral conduction velocity of evoked signals is about 15 m/s, therefore in the A-delta fiber range, and (4) local application of lidocaine abolishes effects of IES. Based on these findings, IES is considered to activate A-delta fibers selectively. In addition to A-delta fibers, we have recently succeeded in selectively stimulating cutaneous C-nociceptors by IES with specific stimulation parameters. Since IES is very easy to use, and non-invasive, it is expected to be a useful tool for a clinical use. Possible clinical application of IES will be discussed. S6-3 Small fiber neuropathy and pain M. Schmelz1 1 Dept. Anesthesiology Mannheim, Heidelberg University, Mannheim, Germany In pain research small fiber neuropathy is often linked to neuropathic pain disregarding that most patients suffering from small fiber neuropathies do not have clinical pain problems. Thus the crucial question arises what are the specific functional and structural markers in neuropathy that would predict pain. Combined studies assessing clinical characteristics, temperature thresholds (quantitative sensory testing) and electrically induced pain, axon reflex erythema and nerve fiber density in skin biopsies were performed in patients with traumatic nerve injuries with and without pain and also in painful thin fiber neuropathy. We found reduced epidermal nerve fiber density correlating to the neuropathy. Moreover, innervation density of the epidermis correlated to temperature thresholds whereas innervation density in the dermis correlated to axon reflex erythema. However no correlation of innervation density and pain levels were found. We conclude that quantitative sensory testing, axon reflex measurements and assessment of skin innervation density are valuable tools to quantify and characterize peripheral neuropathy and link neuronal functions to different layers of the skin. However, the degree of thin fiber neuropathy did not correlate to the clinical pain intensity. In contrast to the functional and histological measures, direct recordings of C-nociceptors in pain patients using microneurography revealed higher level of ongoing activity and a reduction of activity dependent slowing of conduction velocity. Thus, functional changes of nociceptors in patients with neuropathic pain can be detected by microneurography. S6-4 Conduction velocity of C-fibers in humans S. Iwase1 , M. Kondo2 , Y. Kuwahara1 , M. Takata1 , J. Sugenoya1 , T. Mano3 1 Department of Physiology, Aichi Medical University, Aichi, Japan, 2 Department of Neurology, Saiseikai Matsuzaka General Hospital, Matsuzaka, Japan, 3 Gifu University of Medical Science, Japan There are three kinds of C-fibers, microneurographically recorded in humans. One is nociceptive C-fiber, which conducts skin nociceptive sensation. Since nociceptive receptor can be activated by electric stimulation, conduction velocity of nociceptive C-fibers can be measured by the calculation, distance divided by latency. There are two kinds of sympathetic nerve activity microneurographically recordable in humans, muscle sympathetic nerve activity and skin sympathetic nerve activity. These activities are spontaneous and efferent, so conduction velocity cannot be measured by electric stimulation-response relationships. Muscle sympathetic nerve activity is vasoconstrictor, governed by baroreflex. The first report on this activity used the latency from electrocardiographic R-wave to the burst of muscle sympathetic nerve activity. By plotting the length from the lumbar plexus to the recording
Oral Presentations: Symposia Additionally, for clinical application, safety, low cost, and simplicity of use are required. For the nociceptive system, the stimulation method that is fulfilling these requirements is limited. We have developed a method of intra-epidermal electrical stimulation (IES) for the selective activation of cutaneous A-delta fibers. For IES, a concentric bipolar needle electrode which consists of an outer ring 1.2 mm in diameter and inner needle that protrudes 0.1 mm from the outer ring is used. By pressing the electrode against the skin gently, the needle tip is inserted in the epidermis where nociceptors are located, while the outer ring is attached to the skin surface. A weak current passing through the electrode is expected to activate the superficial part of the skin selectively. We have been using this method to investigate the nociceptive system, and found that (1) IES with a very weak current (<0.3 mA) elicits a pricking sensation, (2) IES evoked potentials or magnetic fields that are similar to those evoked by laser stimulation, (3) the peripheral conduction velocity of evoked signals is about 15 m/s, therefore in the A-delta fiber range, and (4) local application of lidocaine abolishes effects of IES. Based on these findings, IES is considered to activate A-delta fibers selectively. In addition to A-delta fibers, we have recently succeeded in selectively stimulating cutaneous C-nociceptors by IES with specific stimulation parameters. Since IES is very easy to use, and non-invasive, it is expected to be a useful tool for a clinical use. Possible clinical application of IES will be discussed. S6-3 Small fiber neuropathy and pain M. Schmelz1 1 Dept. Anesthesiology Mannheim, Heidelberg University, Mannheim, Germany In pain research small fiber neuropathy is often linked to neuropathic pain disregarding that most patients suffering from small fiber neuropathies do not have clinical pain problems. Thus the crucial question arises what are the specific functional and structural markers in neuropathy that would predict pain. Combined studies assessing clinical characteristics, temperature thresholds (quantitative sensory testing) and electrically induced pain, axon reflex erythema and nerve fiber density in skin biopsies were performed in patients with traumatic nerve injuries with and without pain and also in painful thin fiber neuropathy. We found reduced epidermal nerve fiber density correlating to the neuropathy. Moreover, innervation density of the epidermis correlated to temperature thresholds whereas innervation density in the dermis correlated to axon reflex erythema. However no correlation of innervation density and pain levels were found. We conclude that quantitative sensory testing, axon reflex measurements and assessment of skin innervation density are valuable tools to quantify and characterize peripheral neuropathy and link neuronal functions to different layers of the skin. However, the degree of thin fiber neuropathy did not correlate to the clinical pain intensity. In contrast to the functional and histological measures, direct recordings of C-nociceptors in pain patients using microneurography revealed higher level of ongoing activity and a reduction of activity dependent slowing of conduction velocity. Thus, functional changes of nociceptors in patients with neuropathic pain can be detected by microneurography. S6-4 Conduction velocity of C-fibers in humans S. Iwase1 , M. Kondo2 , Y. Kuwahara1 , M. Takata1 , J. Sugenoya1 , T. Mano3 1 Department of Physiology, Aichi Medical University, Aichi, Japan, 2 Department of Neurology, Saiseikai Matsuzaka General Hospital, Matsuzaka, Japan, 3 Gifu University of Medical Science, Japan There are three kinds of C-fibers, microneurographically recorded in humans. One is nociceptive C-fiber, which conducts skin nociceptive sensation. Since nociceptive receptor can be activated by electric stimulation, conduction velocity of nociceptive C-fibers can be measured by the calculation, distance divided by latency. There are two kinds of sympathetic nerve activity microneurographically recordable in humans, muscle sympathetic nerve activity and skin sympathetic nerve activity. These activities are spontaneous and efferent, so conduction velocity cannot be measured by electric stimulation-response relationships. Muscle sympathetic nerve activity is vasoconstrictor, governed by baroreflex. The first report on this activity used the latency from electrocardiographic R-wave to the burst of muscle sympathetic nerve activity. By plotting the length from the lumbar plexus to the recording