Thermal Detection Thresholds of Aδ- and C-Fibre Afferents Activated by Brief CO2 Laser Pulses Applied onto the Human Hairy Skin

Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.

[1]  R. Meyer,et al.  Evidence for two distinct classes of unmyelinated nociceptive afferents in monkey , 1981, Brain Research.

[2]  James N. Campbell,et al.  Latency to detection of first pain , 1983, Brain Research.

[3]  Rolf-Detlef Treede,et al.  Neurophysiological studies of pain pathways in peripheral and central nervous system disorders , 2003, Journal of Neurology.

[4]  B. Bromm,et al.  Responses of human cutaneous afferents to CO2 laser stimuli causing pain , 2004, Experimental Brain Research.

[5]  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.

[6]  Richard A. Meyer,et al.  A Laser Stimulator for the Study of Cutaneous Thermal and Pain Sensations , 1976, IEEE Transactions on Biomedical Engineering.

[7]  A. Mouraux,et al.  Brain responses to signals ascending through C-fibers , 2002 .

[8]  A. V. Zaitsev,et al.  Mathematical Description of Sensorimotor Reaction Time Distribution , 2004, Human Physiology.

[9]  W. Miltner,et al.  Scalp topography of ultralate (C-fibres) evoked potentials following thulium YAG laser stimuli to tiny skin surface areas in humans , 2001, Clinical Neurophysiology.

[10]  J. Ochoa,et al.  The normal sural nerve in man. I. Ultrastructure and numbers of fibres and cells. , 1969, Acta neuropathologica.

[11]  A Mouraux,et al.  Non-phase locked electroencephalogram (EEG) responses to CO2 laser skin stimulations may reflect central interactions between A∂- and C-fibre afferent volleys , 2003, Clinical Neurophysiology.

[12]  G. Cruccu,et al.  EFNS guidelines on neuropathic pain assessment , 2004, European journal of neurology.

[13]  K. O. Johnson,et al.  Coding of incremental changes in skin temperature by a population of warm fibers in the monkey: correlation with intensity discrimination in man. , 1979, Journal of neurophysiology.

[14]  A. Mouraux,et al.  How do we selectively activate skin nociceptors with a high power infrared laser? Physiology and biophysics of laser stimulation , 2003, Neurophysiologie Clinique/Clinical Neurophysiology.

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

[16]  H. E. Torebjörk,et al.  Nociceptors and warm receptors innervated by C fibres in human skin. , 1982, Journal of neurology, neurosurgery, and psychiatry.

[17]  J D HARDY,et al.  Spectral transmittance and reflectance of excised human skin. , 1956, Journal of applied physiology.

[18]  J Ellrich,et al.  C- and A delta-fiber components of heat-evoked cerebral potentials in healthy human subjects. , 1999, Pain.

[19]  André Mouraux,et al.  EEG and laser stimulation as tools for pain research. , 2005, Current opinion in investigational drugs.

[20]  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.

[21]  H G WOLFF,et al.  Influence of skin temperature upon the pain threshold as evoked by thermal radiation. , 1951, A.M.A. archives of neurology and psychiatry.

[22]  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.

[23]  A. Mouraux,et al.  Are laser-evoked brain potentials modulated by attending to first or second pain? , 2007, Pain.

[24]  Gian Domenico Iannetti,et al.  Laser guns and hot plates , 2005, Pain.

[25]  I. Darian‐Smith,et al.  Coding of incremental changes in skin temperature by single warm fibers in the monkey. , 1979, Journal of neurophysiology.

[26]  R. Treede,et al.  Nerve fibre discharges, cerebral potentials and sensations induced by CO2 laser stimulation. , 1984, Human neurobiology.

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

[28]  R. Meyer,et al.  Myelinated nociceptive afferents account for the hyperalgesia that follows a burn to the hand. , 1981, Science.

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

[30]  A. Carmon,et al.  Evoked cerebral responses to noxious thermal stimuli in humans , 1976, Experimental Brain Research.

[31]  L. Plaghki,et al.  The effects of A‐fiber pressure block on perception and neurophysiological correlates of brief non‐painful and painful CO2 laser stimuli in humans , 2003, European journal of pain.

[32]  L. Arendt-Nielsen,et al.  Argon laser induced single cortical responses: a new method to quantify pre-pain and pain perceptions. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[33]  D. Kenshalo,et al.  Periaqueductal gray-evoked dorsal root reflex is frequency dependent , 2003, Brain Research.

[34]  L. Plaghki,et al.  The Fine Tuning of Pain Thresholds: A Sophisticated Double Alarm System , 2010, PloS one.

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

[36]  A. Mouraux,et al.  Refractoriness cannot explain why C-fiber laser-evoked brain potentials are recorded only if concomitant Aδ-fiber activation is avoided , 2004, Pain.