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Measuring conduction velocity of C-fibers in humans by somatosensory cerebral-evoked potentials
International Congress Series 1232 (2002) 213 – 218
Measuring conduction velocity of C-fibers in humans by somatosensory cerebral-evoked potentials Tuan Diep Tran*, Khanh Lam, Minoru Hoshiyama, Ryusuke Kakigi Department of Integrative Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
Abstract The conduction velocity of C-fibers of a peripheral nerve in the upper limb was measured following CO2 laser stimulation of a tiny area of the surface of the skin in a number of normal subjects. A thin aluminum plate with many tiny holes was used as a filter and placed on the skin at the stimulation site. The array of holes allowed the 2-mm laser beam to pass through one to four holes to reach the skin. The physiological background of this method is that the C afferent sensory terminals in the skin have a higher density and lower activation threshold than the Ay-terminals. The value obtained was 1.2 m/s. The finding demonstrated that this noninvasive method is useful for experimental and clinical exploration of the physiological function and pathophysiological role of Cfibers. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Conduction velocity; C-fibers; CO2 laser stimulation; Tiny skin surface area; Laser-evoked potential
1. Introduction The conduction velocities (CV) of Ah-fibers (large-diameter myelinated sensory fibers), and Ay-fibers (small myelinated fibers), of the peripheral nerves are easily measured by the conventional methods of electrical stimulation [1,2] and CO2 laser stimulation [3– 9], respectively. It is, however, difficult to measure the CV of unmyelinated C-fibers [5,8]. Bromm et al. [3– 5] measured the CV of the C-fibers by blocking the myelinated fibers, for example, by applying pressure to the nerve supplying the study area. Towell et al. [10] reported a method that utilizes low-intensity stimulation. Magerl et al. [11] introduced a method based on the heat threshold, feedback-control laser heat, to excite selectively C-fibers. The CV reported by them was 1.3 – 2.4 m/s. However, all these *
Corresponding author. Tel.: +81-564-55-7769; fax: +81-564-52-7913. E-mail address: [email protected] (T.D. Tran).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 8 3 6 - 6
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methods were difficult to perform. Recently, a noninvasive method for the selective activation of C afferent sensory terminals in the skin, by CO2 laser stimulation of a tiny surface area, has been reported [12,13]. The physiological background of this method is that the C afferent sensory terminals in the skin have a higher density and lower activation threshold than the Ay-terminals [14 –16]. The present study measured the CV of the C-fibers of a peripheral nerve in humans using CO2 laser stimulation of a tiny surface area of the skin.
2. Materials and methods Twenty-three healthy volunteers were enrolled in this study (including 20 males and 3 females). Their ages ranged from 26 to 42 (meanFSD: 33.9F4.0) years and their heights from 156 to 180 (169.8F6.1) cm. All the subjects gave informed consent, and the ethical committee at our institute approved the study. None of the subjects suffered from diseases that might affect normal somesthetic perception. A special CO2 laser stimulator was designed by Nippon Infrared Industries (Kawasaki, Japan) to elicit the laser-evoked potentials (LEP). Its maximum power output was 12.5 W, and the laser wavelength was 10.6 Am. The diameter of the irradiation beam was approximately 2 mm. To selectively activate C-fibers, we used a thin aluminum plate (0.1 mm in depth, 40 mm in length and 60 mm in width). In a 2525 mm2 on this plate, 26 parallel lines were drawn every 1 mm, giving 2626 intersections. A total of 676 (2626) tiny holes were drilled at these intersections, each with a diameter of 0.4 mm, which corresponded to an area of 0.125 mm2 for each hole (Fig. 1). This thin plate was then used as a filter and placed on the skin at the site of stimulation and the array of holes allowed the 2-mm laser beam to pass through one to four holes to reach the skin. Furthermore, the stimulus intensity was approximately 7– 10 mJ/mm2 with a 20-ms duration, which caused pressure, touch, or slight pain. The principle of this method was based on those of Bragard et al. [12] and Opsommer et al. [13], but the method was
Fig. 1. The aluminum plate with a total of 676 tiny holes, each with a diameter of 0.4 mm, corresponding to an area of 0.125 mm2. This array of holes allowed the 2-mm laser beam to pass through one to four holes to reach the skin.
T.D. Tran et al. / International Congress Series 1232 (2002) 213–218
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modified by using a thin plate with many small holes drilled into it [17]. To avoid habituation, the irradiated points were shifted slightly for each stimulus and the stimulus rate was set randomly from 0.1 to 0.3 Hz. The amplifier frequency response was from 0.1 to 50 Hz with a 10-AV/cm sensitivity. Ten responses were averaged per recording, and at least three recordings were obtained for each stimulus site. The analysis time was 2048 ms and the sampling rate was 512 Hz. Stimulation was given at two sites: between the first and second metacarpal bones for the distal site (hand), and on the lateral side of the forearm about 5 cm below the line of the anterior cubital for the proximal site (forearm). Both sites were on the left side. The left radial nerve and its superficial branches supply these areas. Exploring electrodes were placed at Cz, according to the international 10 –20 system for recording the LEP, since maximum LEP amplitude is achievable at this site. Impedance was maintained below 5 kV. A reference electrode was placed on the left ear (A1) and a ground electrode was placed on the forehead, and electrooculography was simultaneously recorded for artifact rejection. The sites of stimulation were randomized and balanced. Subjects had a 5 –10min rest before changing to another stimulus site recording, and the room temperature was kept at 24 jC, the sound and light conditions were also regulated. The subjects were calm, vigilant, attentive and relaxed; with their eyes open, and as a safety measure, goggles were worn to protect their eyes from the CO2 laser beam. After confirming the reproducibility of the waveform, all the recordings were group averaged, and the peak latencies of the primary large positive component of the LEP were
Fig. 2. The laser-evoked potentials in response to the CO2 laser stimulation of a tiny surface area of skin, of the hand and forearm in a 36-year-old normal subject. The upper trace is a superimposition of three averages and the lower one is their summed averaged waveform for each stimulation site. The ultra-late P1 peak latency was 884 and 718 ms after hand and forearm non-painful CO2 laser stimulation, respectively. The distance between the two stimulus sites, hand and forearm, was 22 cm. The calculated nerve conduction velocity of C-fibers was 1.3 m/s.
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Table 1 Results of ultra-late LEP following hand and forearm stimulation, and the calculated conduction velocities of the C-fibers
Peak latency (ms) Hand stimulation P1 (ultra-late LEP) Forearm stimulation P1 (ultra-late LEP) Latency difference between hand and forearm stimulation (ms) P1 (ultra-late LEP) Conduction velocity (m/s) C-fibers
MeanFSD
Range
926F78
760 – 1076
717F60
571 – 800
206F44
156 – 317
1.2F0.2
0.8 – 1.5
measured. We termed them P1 potential. Finally, the differences in the peak latencies between the hand- and forearm-stimulated components, and the distance between the two stimulus sites was measured to calculate the CV of the C-fibers.
3. Results The P1 component following non-painful CO2 laser stimulation of a tiny area of the skin was clearly identified in all the subjects. This component was termed ‘‘P1 (ultra-late LEP)’’ (Fig. 2). Its mean peak latency, following hand and forearm stimulation, was very long, 926 and 717 ms, respectively. The P1 component of the painful CO2 laser stimulation ‘‘P1 (late LEP)’’, however, was not recorded in this stimulus condition (Fig. 2). The negative component was identified before P1 (ultra-late LEP), but was very small or absent in 10 out of the 23 subjects, and so was not fully analyzed here. The mean, standard deviation (SD), and range of the peak latencies of P1 (ultra-late LEP), the latency difference of these peaks between hand and forearm stimulation, and the calculated CV of C-fibers of the peripheral radial nerve, are shown in Table 1. The CV was 1.2F0.2 m/s.
4. Discussion When evaluating patients with peripheral neuropathies, it is important to measure the CV of the peripheral nerves. Electrical stimulation is routinely used for the measurement of the large-diameter Ah-fibers. For measuring the CV of the small myelinated Ay-fibers, a very strong electrical stimulation, which activated the Ay- as well as Ah-fibers, was used [18]. However, a CO2 laser beam is the best stimulus as it produces pure thermal and/or painful responses [5,8]. For measuring the CV of the small unmyelinated C-fibers, invasive techniques (microneurograms) and a conduction block of myelinated fibers [3 – 5] have been proposed, but are not routinely used and do not always give reliable results. Recently, Bragard et al. [12] and Opsommer et al. [13] have introduced a simple and noninvasive
T.D. Tran et al. / International Congress Series 1232 (2002) 213–218
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method of selectively activating the C afferent sensory terminals in the skin, by stimulation of a tiny surface area. We adopted and modified this method to measure the CV of the Cfibers of a peripheral nerve. We have attempted to estimate the CV of the C-fibers in humans using ultra-late LEP. We recorded the ultra-late LEP at the proximal and distal stimulation sites of the left arm, which were innervated by the left radial nerve. The superficial branch of the radial nerve is responsible for innervating the skin between the first and second metacarpal bones of the distal stimulation site, and the posterior cutaneous nerve of the forearm, a branch of the radial nerve, is responsible for innervating the skin on the lateral side of the forearm at the proximal stimulation site. Our findings on the waveform and latency of the ultra-late LEP were consistent with the previous reports [4 –7,10 – 13,19]. In these studies, the CV of the C-fibers was 0.5 – 2.4 m/s. The principle of our method was based on that of Bragard et al. [12] and Opsommer et al. [13]. However, instead of only one hole, we used an aluminum plate with a number of tiny holes that could be attached to the skin and reduce the effects of diffraction. We believe that this method is useful for clinical studies, since it is easy and simple, and it can be used for various parts of the body. In conclusion, the CV of the C-fibers of a peripheral nerve was measured, using a special thin aluminum plate with a large number of tiny holes operating as a filter in CO2 laser stimulation. The mean CV of the C-fibers of the radial nerve in normal subjects was 1.2 m/s. We believe that this noninvasive method will be useful not only for research, but also for routine clinical studies.
Acknowledgements We would like to thank Mr. Y. Takeshima for his technical help.
References [1] M.J. Aminoff, A. Eisen, Somatosensory evoked potentials, in: M.J. Aminoff (Ed.), Electro Diagnosis in Clinical Neurology, Churchill Livingstone, New York, 1992, pp. 571 – 603. [2] F. Mauguiere, T. Allison, C. Babiloni, H. Buchner, A.A. Eisen, D.S. Goodin, J. Jones, R. Kakigi, S. Matsuoka, M. Nuwer, P.M. Rossini, H. Shibasaki, Somatosensory evoked potentials, in: G. Deuschl, A.A. Eisen (Eds.), Recommendations for the Practice of Clinical Neurophysiology: Guidelines of the International Federation of Clinical Physiology, Elsevier, Oxford, 1999, pp. 79 – 90 (EEG Suppl. 52). [3] B. Bromm, J. Lorenz, Neurophysiological evaluation of pain, Electroencephalogr. Clin. Neurophysiol. 107 (1998) 227 – 253. [4] B. Bromm, R.D. Treede, Pain related cerebral potentials: late and ultralate components, Int. J. Neurosci. 33 (1987) 15 – 23. [5] B. Bromm, R.D. Treede, Laser-evoked cerebral potentials in the assessment of cutaneous pain sensitivity in normal subjects and patients, Rev. Neurol. 147 (1991) 625 – 643. [6] R. Kakigi, C. Endo, R. Neshige, Y. Kuroda, H. Shibasaki, Estimation of the conduction velocity of Ay-fibers in humans, Muscle Nerve 14 (1991) 1193 – 1196. [7] R. Kakigi, H. Shibasaki, H. Ikeda, R. Neshige, Y. Kuroda, Pain related somatosensory evoked potentials in peripheral neuropathies, Acta Neurol. Scand. 85 (1992) 347 – 352. [8] R. Kakigi, S. Watanabe, H. Yamasaki, Pain related somatosensory evoked potentials, J. Clin. Neurophysiol. 17 (2000) 295 – 308.
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[9] B. Kenton, R. Coger, B. Crue, J. Pinsky, Y. Friedman, A. Carmon, Peripheral fiber correlates to noxious thermal stimulation in humans, Neurosci. Lett. 17 (1980) 301 – 306. [10] A.D. Towell, A.M. Purves, S.G. Boyd, CO2 laser activation of nociceptive and non-nociceptive thermal afferents from hairy and glabrous skin, Pain 66 (1996) 79 – 86. [11] W. Magerl, Z. Ali, J. Ellrich, R.A. Mayer, R.D. Treede, C- and Ay-fiber components of heat-evoked cerebral potentials in healthy human subjects, Pain 82 (1999) 127 – 137. [12] D. Bragard, A.C.N. Chen, L. Plaghki, Direct isolation of ultra-late (C-fibre) evoked brain potentials by CO2 laser stimulation of tiny cutaneous surface areas in man, Neurosci. Lett. 209 (1996) 81 – 84. [13] E. Opsommer, L. Masquelier, L. Plaghki, Determination of nerve conduction velocity of C-fibres in humans from thermal threshold to contact heat (thermode) and from evoked brain potentials to radiant heat (CO2 laser), Neurophysiol. Clin. 29 (1999) 411 – 422. [14] J. Ochoa, W.G.P. Mair, The normal sural nerve in man: I. ultrastructure and numbers of fibres and cells, Acta Neuropathol. (Berlin) 13 (1969) 197 – 216. [15] R.F. Schmidt, H.G. Schaible, K. Messlinger, B. Heppelmann, U. Hanesch, M. Pawlak, Silent and active nociceptors: structure, functions, and clinical implications, in: G.F. Gebhart, D.L. Hammond, T.S. Jensen (Eds.), Proceedings of the 7th World Congress on Pain, IASP Press, Seattle, 1994, pp. 213 – 250. [16] R.D. Treede, R.A. Meyer, R.P. Lesser, Similarity of threshold temperatures for first pain sensation, laserevoked potentials, and nociceptor activation, in: G.F. Gebhart, D.L. Hammond, T.S. Jensen (Eds.), Proceedings of the 7th World Congress on Pain, IASP Press, Seattle, 1994, pp. 857 – 865. [17] T.D. Tran, K. Lam, M. Hoshiyama, R. Kakigi, A new method for measuring the conduction velocities of Ah-, Ay- and C-fibers following electric and CO2 laser stimulation in humans, Neurosci. Lett. 301 (2001) 187 – 190. [18] D. Naka, R. Kakigi, Simple and novel methods for measuring conduction velocity of Ay-fibers in humans, J. Clin. Neurophysiol. 15 (1998) 150 – 153. [19] D. Yarnitsky, J.L. Ochoa, Warm and cold specific somatosensory system. Psychophysical thresholds, reaction times and peripheral conduction velocities, Brain 114 (1991) 1819 – 1826.
Measuring conduction velocity of C-fibers in humans by somatosensory cerebral-evoked potentials Tuan Diep Tran*, Khanh Lam, Minoru Hoshiyama, Ryusuke Kakigi Department of Integrative Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
Abstract The conduction velocity of C-fibers of a peripheral nerve in the upper limb was measured following CO2 laser stimulation of a tiny area of the surface of the skin in a number of normal subjects. A thin aluminum plate with many tiny holes was used as a filter and placed on the skin at the stimulation site. The array of holes allowed the 2-mm laser beam to pass through one to four holes to reach the skin. The physiological background of this method is that the C afferent sensory terminals in the skin have a higher density and lower activation threshold than the Ay-terminals. The value obtained was 1.2 m/s. The finding demonstrated that this noninvasive method is useful for experimental and clinical exploration of the physiological function and pathophysiological role of Cfibers. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Conduction velocity; C-fibers; CO2 laser stimulation; Tiny skin surface area; Laser-evoked potential
1. Introduction The conduction velocities (CV) of Ah-fibers (large-diameter myelinated sensory fibers), and Ay-fibers (small myelinated fibers), of the peripheral nerves are easily measured by the conventional methods of electrical stimulation [1,2] and CO2 laser stimulation [3– 9], respectively. It is, however, difficult to measure the CV of unmyelinated C-fibers [5,8]. Bromm et al. [3– 5] measured the CV of the C-fibers by blocking the myelinated fibers, for example, by applying pressure to the nerve supplying the study area. Towell et al. [10] reported a method that utilizes low-intensity stimulation. Magerl et al. [11] introduced a method based on the heat threshold, feedback-control laser heat, to excite selectively C-fibers. The CV reported by them was 1.3 – 2.4 m/s. However, all these *
Corresponding author. Tel.: +81-564-55-7769; fax: +81-564-52-7913. E-mail address: [email protected] (T.D. Tran).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 8 3 6 - 6
214
T.D. Tran et al. / International Congress Series 1232 (2002) 213–218
methods were difficult to perform. Recently, a noninvasive method for the selective activation of C afferent sensory terminals in the skin, by CO2 laser stimulation of a tiny surface area, has been reported [12,13]. The physiological background of this method is that the C afferent sensory terminals in the skin have a higher density and lower activation threshold than the Ay-terminals [14 –16]. The present study measured the CV of the C-fibers of a peripheral nerve in humans using CO2 laser stimulation of a tiny surface area of the skin.
2. Materials and methods Twenty-three healthy volunteers were enrolled in this study (including 20 males and 3 females). Their ages ranged from 26 to 42 (meanFSD: 33.9F4.0) years and their heights from 156 to 180 (169.8F6.1) cm. All the subjects gave informed consent, and the ethical committee at our institute approved the study. None of the subjects suffered from diseases that might affect normal somesthetic perception. A special CO2 laser stimulator was designed by Nippon Infrared Industries (Kawasaki, Japan) to elicit the laser-evoked potentials (LEP). Its maximum power output was 12.5 W, and the laser wavelength was 10.6 Am. The diameter of the irradiation beam was approximately 2 mm. To selectively activate C-fibers, we used a thin aluminum plate (0.1 mm in depth, 40 mm in length and 60 mm in width). In a 2525 mm2 on this plate, 26 parallel lines were drawn every 1 mm, giving 2626 intersections. A total of 676 (2626) tiny holes were drilled at these intersections, each with a diameter of 0.4 mm, which corresponded to an area of 0.125 mm2 for each hole (Fig. 1). This thin plate was then used as a filter and placed on the skin at the site of stimulation and the array of holes allowed the 2-mm laser beam to pass through one to four holes to reach the skin. Furthermore, the stimulus intensity was approximately 7– 10 mJ/mm2 with a 20-ms duration, which caused pressure, touch, or slight pain. The principle of this method was based on those of Bragard et al. [12] and Opsommer et al. [13], but the method was
Fig. 1. The aluminum plate with a total of 676 tiny holes, each with a diameter of 0.4 mm, corresponding to an area of 0.125 mm2. This array of holes allowed the 2-mm laser beam to pass through one to four holes to reach the skin.
T.D. Tran et al. / International Congress Series 1232 (2002) 213–218
215
modified by using a thin plate with many small holes drilled into it [17]. To avoid habituation, the irradiated points were shifted slightly for each stimulus and the stimulus rate was set randomly from 0.1 to 0.3 Hz. The amplifier frequency response was from 0.1 to 50 Hz with a 10-AV/cm sensitivity. Ten responses were averaged per recording, and at least three recordings were obtained for each stimulus site. The analysis time was 2048 ms and the sampling rate was 512 Hz. Stimulation was given at two sites: between the first and second metacarpal bones for the distal site (hand), and on the lateral side of the forearm about 5 cm below the line of the anterior cubital for the proximal site (forearm). Both sites were on the left side. The left radial nerve and its superficial branches supply these areas. Exploring electrodes were placed at Cz, according to the international 10 –20 system for recording the LEP, since maximum LEP amplitude is achievable at this site. Impedance was maintained below 5 kV. A reference electrode was placed on the left ear (A1) and a ground electrode was placed on the forehead, and electrooculography was simultaneously recorded for artifact rejection. The sites of stimulation were randomized and balanced. Subjects had a 5 –10min rest before changing to another stimulus site recording, and the room temperature was kept at 24 jC, the sound and light conditions were also regulated. The subjects were calm, vigilant, attentive and relaxed; with their eyes open, and as a safety measure, goggles were worn to protect their eyes from the CO2 laser beam. After confirming the reproducibility of the waveform, all the recordings were group averaged, and the peak latencies of the primary large positive component of the LEP were
Fig. 2. The laser-evoked potentials in response to the CO2 laser stimulation of a tiny surface area of skin, of the hand and forearm in a 36-year-old normal subject. The upper trace is a superimposition of three averages and the lower one is their summed averaged waveform for each stimulation site. The ultra-late P1 peak latency was 884 and 718 ms after hand and forearm non-painful CO2 laser stimulation, respectively. The distance between the two stimulus sites, hand and forearm, was 22 cm. The calculated nerve conduction velocity of C-fibers was 1.3 m/s.
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Table 1 Results of ultra-late LEP following hand and forearm stimulation, and the calculated conduction velocities of the C-fibers
Peak latency (ms) Hand stimulation P1 (ultra-late LEP) Forearm stimulation P1 (ultra-late LEP) Latency difference between hand and forearm stimulation (ms) P1 (ultra-late LEP) Conduction velocity (m/s) C-fibers
MeanFSD
Range
926F78
760 – 1076
717F60
571 – 800
206F44
156 – 317
1.2F0.2
0.8 – 1.5
measured. We termed them P1 potential. Finally, the differences in the peak latencies between the hand- and forearm-stimulated components, and the distance between the two stimulus sites was measured to calculate the CV of the C-fibers.
3. Results The P1 component following non-painful CO2 laser stimulation of a tiny area of the skin was clearly identified in all the subjects. This component was termed ‘‘P1 (ultra-late LEP)’’ (Fig. 2). Its mean peak latency, following hand and forearm stimulation, was very long, 926 and 717 ms, respectively. The P1 component of the painful CO2 laser stimulation ‘‘P1 (late LEP)’’, however, was not recorded in this stimulus condition (Fig. 2). The negative component was identified before P1 (ultra-late LEP), but was very small or absent in 10 out of the 23 subjects, and so was not fully analyzed here. The mean, standard deviation (SD), and range of the peak latencies of P1 (ultra-late LEP), the latency difference of these peaks between hand and forearm stimulation, and the calculated CV of C-fibers of the peripheral radial nerve, are shown in Table 1. The CV was 1.2F0.2 m/s.
4. Discussion When evaluating patients with peripheral neuropathies, it is important to measure the CV of the peripheral nerves. Electrical stimulation is routinely used for the measurement of the large-diameter Ah-fibers. For measuring the CV of the small myelinated Ay-fibers, a very strong electrical stimulation, which activated the Ay- as well as Ah-fibers, was used [18]. However, a CO2 laser beam is the best stimulus as it produces pure thermal and/or painful responses [5,8]. For measuring the CV of the small unmyelinated C-fibers, invasive techniques (microneurograms) and a conduction block of myelinated fibers [3 – 5] have been proposed, but are not routinely used and do not always give reliable results. Recently, Bragard et al. [12] and Opsommer et al. [13] have introduced a simple and noninvasive
T.D. Tran et al. / International Congress Series 1232 (2002) 213–218
217
method of selectively activating the C afferent sensory terminals in the skin, by stimulation of a tiny surface area. We adopted and modified this method to measure the CV of the Cfibers of a peripheral nerve. We have attempted to estimate the CV of the C-fibers in humans using ultra-late LEP. We recorded the ultra-late LEP at the proximal and distal stimulation sites of the left arm, which were innervated by the left radial nerve. The superficial branch of the radial nerve is responsible for innervating the skin between the first and second metacarpal bones of the distal stimulation site, and the posterior cutaneous nerve of the forearm, a branch of the radial nerve, is responsible for innervating the skin on the lateral side of the forearm at the proximal stimulation site. Our findings on the waveform and latency of the ultra-late LEP were consistent with the previous reports [4 –7,10 – 13,19]. In these studies, the CV of the C-fibers was 0.5 – 2.4 m/s. The principle of our method was based on that of Bragard et al. [12] and Opsommer et al. [13]. However, instead of only one hole, we used an aluminum plate with a number of tiny holes that could be attached to the skin and reduce the effects of diffraction. We believe that this method is useful for clinical studies, since it is easy and simple, and it can be used for various parts of the body. In conclusion, the CV of the C-fibers of a peripheral nerve was measured, using a special thin aluminum plate with a large number of tiny holes operating as a filter in CO2 laser stimulation. The mean CV of the C-fibers of the radial nerve in normal subjects was 1.2 m/s. We believe that this noninvasive method will be useful not only for research, but also for routine clinical studies.
Acknowledgements We would like to thank Mr. Y. Takeshima for his technical help.
References [1] M.J. Aminoff, A. Eisen, Somatosensory evoked potentials, in: M.J. Aminoff (Ed.), Electro Diagnosis in Clinical Neurology, Churchill Livingstone, New York, 1992, pp. 571 – 603. [2] F. Mauguiere, T. Allison, C. Babiloni, H. Buchner, A.A. Eisen, D.S. Goodin, J. Jones, R. Kakigi, S. Matsuoka, M. Nuwer, P.M. Rossini, H. Shibasaki, Somatosensory evoked potentials, in: G. Deuschl, A.A. Eisen (Eds.), Recommendations for the Practice of Clinical Neurophysiology: Guidelines of the International Federation of Clinical Physiology, Elsevier, Oxford, 1999, pp. 79 – 90 (EEG Suppl. 52). [3] B. Bromm, J. Lorenz, Neurophysiological evaluation of pain, Electroencephalogr. Clin. Neurophysiol. 107 (1998) 227 – 253. [4] B. Bromm, R.D. Treede, Pain related cerebral potentials: late and ultralate components, Int. J. Neurosci. 33 (1987) 15 – 23. [5] B. Bromm, R.D. Treede, Laser-evoked cerebral potentials in the assessment of cutaneous pain sensitivity in normal subjects and patients, Rev. Neurol. 147 (1991) 625 – 643. [6] R. Kakigi, C. Endo, R. Neshige, Y. Kuroda, H. Shibasaki, Estimation of the conduction velocity of Ay-fibers in humans, Muscle Nerve 14 (1991) 1193 – 1196. [7] R. Kakigi, H. Shibasaki, H. Ikeda, R. Neshige, Y. Kuroda, Pain related somatosensory evoked potentials in peripheral neuropathies, Acta Neurol. Scand. 85 (1992) 347 – 352. [8] R. Kakigi, S. Watanabe, H. Yamasaki, Pain related somatosensory evoked potentials, J. Clin. Neurophysiol. 17 (2000) 295 – 308.
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[9] B. Kenton, R. Coger, B. Crue, J. Pinsky, Y. Friedman, A. Carmon, Peripheral fiber correlates to noxious thermal stimulation in humans, Neurosci. Lett. 17 (1980) 301 – 306. [10] A.D. Towell, A.M. Purves, S.G. Boyd, CO2 laser activation of nociceptive and non-nociceptive thermal afferents from hairy and glabrous skin, Pain 66 (1996) 79 – 86. [11] W. Magerl, Z. Ali, J. Ellrich, R.A. Mayer, R.D. Treede, C- and Ay-fiber components of heat-evoked cerebral potentials in healthy human subjects, Pain 82 (1999) 127 – 137. [12] D. Bragard, A.C.N. Chen, L. Plaghki, Direct isolation of ultra-late (C-fibre) evoked brain potentials by CO2 laser stimulation of tiny cutaneous surface areas in man, Neurosci. Lett. 209 (1996) 81 – 84. [13] E. Opsommer, L. Masquelier, L. Plaghki, Determination of nerve conduction velocity of C-fibres in humans from thermal threshold to contact heat (thermode) and from evoked brain potentials to radiant heat (CO2 laser), Neurophysiol. Clin. 29 (1999) 411 – 422. [14] J. Ochoa, W.G.P. Mair, The normal sural nerve in man: I. ultrastructure and numbers of fibres and cells, Acta Neuropathol. (Berlin) 13 (1969) 197 – 216. [15] R.F. Schmidt, H.G. Schaible, K. Messlinger, B. Heppelmann, U. Hanesch, M. Pawlak, Silent and active nociceptors: structure, functions, and clinical implications, in: G.F. Gebhart, D.L. Hammond, T.S. Jensen (Eds.), Proceedings of the 7th World Congress on Pain, IASP Press, Seattle, 1994, pp. 213 – 250. [16] R.D. Treede, R.A. Meyer, R.P. Lesser, Similarity of threshold temperatures for first pain sensation, laserevoked potentials, and nociceptor activation, in: G.F. Gebhart, D.L. Hammond, T.S. Jensen (Eds.), Proceedings of the 7th World Congress on Pain, IASP Press, Seattle, 1994, pp. 857 – 865. [17] T.D. Tran, K. Lam, M. Hoshiyama, R. Kakigi, A new method for measuring the conduction velocities of Ah-, Ay- and C-fibers following electric and CO2 laser stimulation in humans, Neurosci. Lett. 301 (2001) 187 – 190. [18] D. Naka, R. Kakigi, Simple and novel methods for measuring conduction velocity of Ay-fibers in humans, J. Clin. Neurophysiol. 15 (1998) 150 – 153. [19] D. Yarnitsky, J.L. Ochoa, Warm and cold specific somatosensory system. Psychophysical thresholds, reaction times and peripheral conduction velocities, Brain 114 (1991) 1819 – 1826.