Activation of C-fiber nociceptors by low-power diode laser

Abstract

The criteria for diagnosis of definite neuropathic pain depend on a plausible neuroanatomic distribution of the pain, a history suggestive of somatosensory lesion or disease and at least one objective confirmatory test of the existence of such relevant somatosensory lesion or disease 1 . Somatosensory evoked potentials (SEPs) and laser evoked potentials (LEPs) are becoming "standards" to document possible involvement of the neural systems in patients with neuropathic pain: the sensitivity of LEP to small lesions on the involved pathways are conferring to it medical legal value in some European countries 2 . Although exquisitely sensitive to spinothalamic impairments, LEPs are considered as a supportive tool to diagnose small fiber neuropathies (given their poor localization value) 3. These observations suggest that the search for alternative stimulus sources to obtain LEPs, aiming to reduce the risks of complications (e.g. skin burns) and the costs of the procedure, are important to increase the availability of these exams; further, the stimulus should be able to allow separate evaluations of Aδ and C fibers.Laser heat stimulators have been extensively used to study time-locked nociception responses, as they provide a near-ideal method to selectively activate cutaneous Aδ-fiber and C-fiber nociceptors. The high power outputs of lasers, which allow fast heat ramps, concomitantly activate these two systems and produce a dual perception compatible with conduction in small myelinated Aδ and unmyelinated C fibers 4 . Cortical responses to high intensity stimulation, however, do not reflect such dual activation. Scalp recordings of LEP show a major negative-positive wave (N2-P2) in the latency range of 200-400 ms when stimulating the hand dorsum. These results have been associated with Aδ-fiber activity, AbstrACtObjective: The evaluation of selective activation of C-fibers to record evoked potentials using the association of low-power diode laser (810 nm), tiny-area stimulation and skin-blackening. Method: Laser-evoked potentials (LEPs) were obtained from 20 healthy young subjects. An aluminum plate with one thin hole was attached to the laser probe to provide tiny-area stimulation of the hand dorsum and the stimulated area was covered with black ink. Results: The mean intensity used for eliciting the ultra-late laser-evoked potential (ULEP) was 70 ± 32 mW. All subjects showed a clear biphasic potential that comprised a negative peak (806 ± 61 ms) and a positive deflection (1033 ± 60 ms), corresponding to the ULEP related to C-fiber activation. Conclusion: C-fiber-evoked responses can be obtained using a very low-power diode laser when stimulation is applied to tiny areas of darkened skin. This strategy offers a non-invasive and easy methodology that minimizes damage to the tissue.Keywords: laser-evoked potentials, C-fibers, nociception, pain perception. resumo Objetivo: Avaliação da ativação de fibras C para o registro de potenciais evocados utilizando-se laser de baixa potência, áreas pequenas de estimulação e escu...

Single and double pain responses to individually titrated ultra-short laser stimulation in humans

“…We did not use neuronal or cerebrocortical electrophysiological measurements – in addition to individual pain scoring – to distinguish between first (Aδ-fibre mediated) and second (C-fibre mediated) pain responses, based on differences in their nociceptive response latency and neuronal transmission properties. Nevertheless, the approximately one-second delay of each reported single pain, and second double pain, sensation – interpreted to reflect C-fibre mediated transmission – is consistent with recent neurophysiological findings [10]. Moreover, the induction of two pain responses, consistently well separated in time at bedside, by a single nociceptive stimulus, conforms to simultaneous activation of Aδ- and C-fibre fibres.…”

“…Results reported here were obtained in more study participants compared with most previous studies based on laser-induced pain [1, 3–10, 14], except for two previous [16, 18] and one recent [19] studies in similar numbers of subjects. The risk for carry-over effects was reduced by allowing minute-long time intervals between stimulations to avoid overlapping of subsequent pain responses.…”

“…Hence, the short-lasting pulses of laser stimulation used in the present and previous [3, 5–9] studies allow both pain components to be independently evaluated, provided that the temperature thresholds of Aδ- and C-fibre nociceptors are both exceeded. Higher separation in time between the first and second pain responses is achieved by inducing pain in the foot, as done in the present and previous [3, 7, 16] studies, instead of in the hand [1, 4–6, 8–10, 14, 15, 18, 19], considering the up to 35% more delayed transmission of second (C-fibre mediated) pain along the estimated 80–100 cm axonal distance between the plantar arc and the lumbosacral spinal cord [3, 7, 16].…”

“…Despite being widely used in research and clinical practice, established bedside tools for pain scoring have been used in few previous studies on nociceptive pain induced by laser stimulation [4, 8, 10, 14, 19], and mainly with assessment of pain intensity on eleven-level visual analogue [10] or numeric rating [4, 14, 19] scales, i.e. with lower resolution than in the present study.…”

“…Ultra-short laser stimulation with a carbon dioxide (CO 2 ) laser meets these criteria and has been used to induce selective activation of C-fibres in humans [3–5], mainly based on different thermal thresholds of Aδ- and C-fibre nociceptors. It has also been used to evoke separate pain responses mediated by Aδ- and C-fibres [3, 5–9], based on differences in nociceptive response latency and neuronal conduction velocity, and assessed by visual analogue scale (VAS) scoring [8, 10], in humans.…”