Unmyelinated trigeminal pathways as assessed by laser stimuli in humans.

Laser pulses excite superficial free nerve endings innervated by small-myelinated (Adelta) and unmyelinated (C) fibres. Whereas laser-evoked scalp potentials (LEPs) are now reliably used to assess function of the Adelta-fibre nociceptive pathways in patients with peripheral or central lesions, the selective activation of C-fibre receptors and recording of the related brain potentials remain difficult. To investigate trigeminal C-fibre function, we directed laser pulses to the facial skin and studied sensory perception and scalp evoked potentials related to Adelta- or C-fibre activation in healthy humans and patients--one having a bilateral facial palsy, two a trigeminal neuropathy, and two a Wallenberg syndrome. We also measured afferent conduction velocity and, with source analysis, studied the brain generators. Whereas laser pulses of low intensity and small irradiated area elicited pinprick sensations and standard Adelta-LEPs, laser pulses of very-low intensity and large irradiated area elicited warmth sensations and scalp potentials with a latency compatible with C-fibre conduction (negative wave 280 ms, positive wave 380 ms); the estimated conduction velocity was 1.2 m/s. The main waves of the scalp potentials originated from the anterior cingulate gyrus; they were preceded by activity in the opercular region and followed by activity in the insular region. The patient with bilateral facial palsy, who had absent trigeminal-facial reflexes, had normal Adelta- and C-related scalp potentials; the patients with trigeminal neuropathy, characterized by loss of myelinated and sparing of unmyelinated fibres, had absent Adelta- but normal C-related potentials; and the patients with Wallenberg syndrome had absent Adelta- and C-related potentials. We conclude that laser pulses with appropriate characteristics evoke brain potentials related to the selective activation of trigeminal nociceptive Adelta or thermal C fibres. The trigeminal territory yields rewarding LEP findings owing to the high density of thermal receptors and, because the short conduction distance, minimizes the problem of signal dispersion along slow-conducting unmyelinated afferents. The opercular-insular region and the cingulate gyrus are involved in the processing of C-fibre trigeminal inputs. The method we describe may prove useful in patients with lesions affecting the trigeminal thermal pain pathways.

[1]  A Berardelli,et al.  Functional organization of the trigeminal motor system in man. A neurophysiological study. , 1989, Brain : a journal of neurology.

[2]  M Manfredi,et al.  Assessment of trigeminal small‐fiber function: brain and reflex responses evoked by CO2‐laser stimulation , 1999, Muscle & nerve.

[3]  M. Manfredi,et al.  Conduction velocity of the human spinothalamic tract as assessed by laser evoked potentials , 2000, Neuroreport.

[4]  R. Kakigi,et al.  Conduction velocity of the spinothalamic tract in humans as assessed by CO2 laser stimulation of C-fibers , 2001, Neuroscience Letters.

[5]  H. S. Gasser UNMEDULLATED FIBERS ORIGINATING IN DORSAL ROOT GANGLIA , 1950, The Journal of general physiology.

[6]  B. Green,et al.  "Warmth-insensitive fields": evidence of sparse and irregular innervation of human skin by the warmth sense. , 1998, Somatosensory & motor research.

[7]  L. Plaghki,et al.  Direct isolation of ultra-late (C-fibre) evoked brain potentials by CO2 laser stimulation of tiny cutaneous surface areas in man , 1996, Neuroscience Letters.

[8]  L. Arendt-Nielsen Second pain event related potentials to argon laser stimuli: recording and quantification. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[9]  R. Treede,et al.  Evoked cerebral potential correlates of C-fibre activity in man , 1983, Neuroscience Letters.

[10]  Hiroshi Shibasaki,et al.  Primary somatosensory cortex is actively involved in pain processing in human , 2000, Brain Research.

[11]  Massimiliano Valeriani,et al.  Characterizing somatosensory evoked potential sources with dipole models: Advantages and limitations , 2001, Muscle & nerve.

[12]  Joachim Gross,et al.  Cortical representation of first and second pain sensation in humans , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  N. Blumen,et al.  Sensory determinants of thermal pain. , 2002, Brain : a journal of neurology.

[14]  R. Meyer,et al.  Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold. , 1995, The Journal of physiology.

[15]  Walter Magerl,et al.  C- and Aδ-fiber components of heat-evoked cerebral potentials in healthy human subjects , 1999, Pain.

[16]  G. Romani,et al.  Auditory evoked magnetic fields and electric potentials , 1990 .

[17]  M. Manfredi,et al.  Small-fiber dysfunction in trigeminal neuralgia , 2001, Neurology.

[18]  A. Carmon,et al.  Peripheral fiber correlates to noxious thermal stimulation in humans , 1980, Neuroscience Letters.

[19]  F. Mauguière,et al.  Scalp topography and dipolar source modelling of potentials evoked by CO2 laser stimulation of the hand. , 1996, Electroencephalography and clinical neurophysiology.

[20]  J T Whitton,et al.  The thickness of the epidermis , 1973, The British journal of dermatology.

[21]  H. E. Torebjörk,et al.  Functional Attributes Discriminating Mechano-Insensitive and Mechano-Responsive C Nociceptors in Human Skin , 1999, The Journal of Neuroscience.

[22]  R. Treede,et al.  Equivalent electrical source analysis of pain-related somatosensory evoked potentials elicited by a CO2 laser. , 1993, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[23]  George Paxinos,et al.  Atlas of the human brainstem , 1995 .

[24]  R. Hughes,et al.  Trigeminal sensory neuropathy. A study of 22 cases. , 1987, Brain : a journal of neurology.

[25]  R. Treede,et al.  Laser-evoked cerebral potentials in the assessment of cutaneous pain sensitivity in normal subjects and patients. , 1991, Revue neurologique.

[26]  C. Büchel,et al.  Dissociable Neural Responses Related to Pain Intensity, Stimulus Intensity, and Stimulus Awareness within the Anterior Cingulate Cortex: A Parametric Single-Trial Laser Functional Magnetic Resonance Imaging Study , 2002, The Journal of Neuroscience.

[27]  M Nordin,et al.  Low‐threshold mechanoreceptive and nociceptive units with unmyelinated (C) fibres in the human supraorbital nerve. , 1990, The Journal of physiology.

[28]  L. Plaghki,et al.  Determination of nerve conduction velocity of C-fibres in humans from thermal thresholds to contact heat (thermode) and from evoked brain potentials to radiant heat (CO2 laser) , 1999, Neurophysiologie Clinique/Clinical Neurophysiology.

[29]  R. Treede,et al.  Ultralate cerebral potentials as correlates of delayed pain perception: observation in a case of neurosyphilis. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[30]  M. Leandri Generator sites of early scalp potentials evoked from the three trigeminal branches. , 1998, Journal of neurosurgery.

[31]  J. Spiegel,et al.  Clinical evaluation criteria for the assessment of impaired pain sensitivity by thulium-laser evoked potentials , 2000, Clinical Neurophysiology.

[32]  R. Treede,et al.  Cerebral potentials evoked by painful, laser stimuli in patients with syringomyelia. , 1991, Brain : a journal of neurology.

[33]  R Kakigi,et al.  Cerebral activation by the signals ascending through unmyelinated C-fibers in humans: a magnetoencephalographic study , 2002, Neuroscience.

[34]  Koji Inui,et al.  Pain-related magnetic fields evoked by intra-epidermal electrical stimulation in humans , 2002, Clinical Neurophysiology.

[35]  M. Manfredi,et al.  Intracranial stimulation of the trigeminal nerve in man. III. Sensory potentials. , 1987, Journal of neurology, neurosurgery, and psychiatry.

[36]  H. Freund,et al.  Parallel activation of primary and secondary somatosensory cortices in human pain processing. , 1999, Journal of neurophysiology.

[37]  J. Lefaucheur,et al.  Laser evoked potentials using the Nd:YAG laser , 2001, Muscle & nerve.

[38]  D. Yarnitsky,et al.  Simultaneous recording of late and ultra-late pain evoked potentials in fibromyalgia , 2001, Clinical Neurophysiology.

[39]  M. Scherg Fundamentals if dipole source potential analysis , 1990 .

[40]  R. Meyer,et al.  Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin. , 1995, The Journal of physiology.

[41]  F. Mauguière,et al.  Sources of cortical responses to painful CO2 laser skin stimulation of the hand and foot in the human brain , 2000, Clinical Neurophysiology.

[42]  H. S. Gasser PROPERTIES OF DORSAL ROOT UNMEDULLATED FIBERS ON THE TWO SIDES OF THE GANGLION , 1955, The Journal of general physiology.

[43]  A. D. Towell,et al.  CO2 laser activation of nociceptive and non-nociceptive thermal afferents from hairy and glabrous skin , 1996, Pain.

[44]  A. Chen,et al.  Brain electrical source analysis of laser evoked potentials in response to painful trigeminal nerve stimulation. , 1995, Electroencephalography and clinical neurophysiology.

[45]  L. Arendt-Nielsen First pain event related potentials to argon laser stimuli: recording and quantification. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[46]  M. Harris,et al.  Trigeminal sensory neuropathy. , 1969, The New England journal of medicine.

[47]  B. Bromm,et al.  Laser evoked brain potentials in response to painful trigeminal nerve activation. , 1995, The International journal of neuroscience.

[48]  B. Bromm,et al.  Ultralate cerebral potentials in a patient with hereditary motor and sensory neuropathy type I indicate preserved C-fibre function. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[49]  C Büchel,et al.  Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. , 2002, Brain : a journal of neurology.

[50]  H Shibasaki,et al.  Estimation of conduction velocity of the spino-thalamic tract in man. , 1991, Electroencephalography and clinical neurophysiology.

[51]  G D Iannetti,et al.  Evidence of a specific spinal pathway for the sense of warmth in humans. , 2003, Journal of neurophysiology.

[52]  M. Manfredi,et al.  Nociceptive quality of the laser-evoked blink reflex in humans. , 2002, Journal of neurophysiology.

[53]  A. Dickenson,et al.  Facial thermal input to the trigeminal spinal nucleus of rabbits and rats , 1979, The Journal of comparative neurology.

[54]  J. Ochoa,et al.  Warm and cold specific somatosensory systems. Psychophysical thresholds, reaction times and peripheral conduction velocities. , 1991, Brain : a journal of neurology.

[55]  G. Cruccu Intracranial stimulation of the trigeminal nerve in man. I. Direct motor responses. , 1986, Journal of neurology, neurosurgery, and psychiatry.

[56]  K. O. Johnson,et al.  Warm fibers innervating palmar and digital skin of the monkey: responses to thermal stimuli. , 1979, Journal of neurophysiology.

[57]  G. Schaltenbrand,et al.  Atlas for Stereotaxy of the Human Brain , 1977 .

[58]  Terry M. Peters,et al.  3D statistical neuroanatomical models from 305 MRI volumes , 1993, 1993 IEEE Conference Record Nuclear Science Symposium and Medical Imaging Conference.

[59]  D Bowsher,et al.  Intracranial stimulation of the trigeminal nerve in man. II. Reflex responses. , 1986, Journal of neurology, neurosurgery, and psychiatry.

[60]  R. Dubner,et al.  Response of unmyelinated (C) polymodal nociceptors to thermal stimuli applied to monkey's face , 1976 .

[61]  R. Kakigi,et al.  Pain-related somatosensory evoked potentials in syringomyelia. , 1991, Brain : a journal of neurology.

[62]  W. Miltner,et al.  Dipole analysis of ultralate (C-fibres) evoked potentials after laser stimulation of tiny cutaneous surface areas in humans , 2001, Neuroscience Letters.

[63]  R. LaMotte,et al.  Comparison of responses of warm and nociceptive C-fiber afferents in monkey with human judgments of thermal pain. , 1978, Journal of neurophysiology.

[64]  Topographical distribution of pinprick and warmth thresholds to CO2 laser stimulation on the human skin , 2000, Neuroscience Letters.

[65]  R. Kakigi,et al.  Pain‐related somatosensory evoked potentials following CO2 laser stimulation in peripheral neuropathies , 1992, Acta neurologica Scandinavica.