Unmyelinated trigeminal pathways as assessed by laser stimuli in humans

Giorgio Cruccu, E. Pennisi, A. Truini, G. D. Iannetti, A. Romaniello, D. Le Pera, L. De Armas, M. Leandri, M. Manfredi, M. Valeriani

Research output: Contribution to journalArticlepeer-review


Laser pulses excite superficial free nerve endings innervated by small-myelinated (Aδ) and unmyelinated (C) fibres. Whereas laser-evoked scalp potentials (LEPs) are now reliably used to assess function of the Aδ-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 Aδ- 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 Aδ-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 Aδ- and C-related scalp potentials; the patients with trigeminal neuropathy, characterized by loss of myelinated and sparing of unmyelinated fibres, had absent Aδ- but normal C-related potentials; and the patients with Wallenberg syndrome had absent Aδ- and C-related potentials. We conclude that laser pulses with appropriate characteristics evoke brain potentials related to the selective activation of trigeminal nociceptive Aδ 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.

Original languageEnglish
Pages (from-to)2246-2256
Number of pages11
Issue number10
Publication statusPublished - Oct 2003


  • Laser evoked potentials
  • Thermal-pain perception
  • Trigeminal nerve
  • Trigeminal nerve biopsy
  • Unmyelinated fibres

ASJC Scopus subject areas

  • Neuroscience(all)


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