However, damage to the nociceptive pathways is not a sufficient condition for CNP to occur, as lesions entailing identical deficits may induce chronic pain in some subjects and not in others.^6–9 These differences may arise in part from genetic susceptibility¹⁰ and in part from pathophysiological dissimilarities that are not detected by standard clinical exams, but may be disclosed by more sophisticated analyses. The proteiform nature of mechanisms triggered by a given lesion is supported by the variety of physiological responses that can be obtained in patients with similar anatomical damage. This has prompted the search for neurophysiological techniques selective for spinothalamic pathways and powerful enough to detect subtle abnormalities in their function.

The Problem of Selective Stimulation of Nociceptive Afferents
Standard neurophysiological responses, i.e. nerve conduction studies and somatosensory-evoked potentials (SEPs), do not selectively assess the function of the thin fibres that convey pain sensations, because electrical stimuli preferentially excite the large, non-nociceptive afferents with the lowest electrical threshold (Aα and Aβ fibres). Special techniques have been proposed to improve the selectivity of electrical stimuli for pain pathways, such as selective blocks of large fibres^11–12 and intra-neural or intra-epidermal stimulation.^13–14

However, all of these techniques have significant technical limitations, are confined to restricted territories and whether they provide a reliable specific correlate of the nociceptive input is controversial. Radiant-heat stimulation can circumvent these difficulties by providing selective activation of Aδ and C thermosensitive nociceptors, without concomitant activation of mechano-receptors. However, most common sources of thermal stimulation, such as light bulbs or Xenon lamps, cannot activate nociceptors synchronously enough to allow the recording of neurophysiological responses.¹⁵

Monochromatic high-intensity light sources provided by laser stimulators eliminate most of these problems. Laser stimulators are able to deliver brief (1–100ms) pulses that rapidly raise the temperature in the superficial layers of the hairy skin and excite type II mechano-thermal nociceptors related to small myelinated (AMH) or unmyelinated (CMH) fibres, as well as thermal C receptors (C warmth units). Gas-state (CO₂, argon) or solid-state laser stimulators – yttrium aluminium garnet (YAG) or yttrium aluminum perovskite (YAP) – are the most commonly used.

Although laser stimuli most often simultaneously excite Aδ and C receptors, both the sensation and the concomitant laser-evoked cerebral potentials (LEPs) reflect, almost exclusively, the transmission by Aδ channels. The reason for this is beyond the purpose of this paper, but the interested reader can consult detailed papers on this matter.^16–17 Selective excitation of the amyelinic C fibres can be achieved by diverse procedures, mainly based on the elimination of the Aδ component by a pressure-block,¹⁸ stimulation of tiny skin areas¹⁹ or stimulation of large areas at low intensity.^20–21 All of these manipulations yield the so-called ‘ultra-late’ LEPs, rising to about 1,000ms after stimulation and depending exclusively on C-fibre activation.

Laser-evoked Potentials in Central Neuropathic Pain
The value of LEPs in the diagnosis of neuropathic pain relies on their aptitude to detect dysfunction of pain and temperature pathways, which is the basis of CNP syndrome development. During the 1990s, extensive validation efforts were carried out to record LEPs in proven lesions of the nervous system, which showed that LEPs can detect even minute injury of the spinothalamic pathways provided that the stimulus is correctly applied to the affected regions. This has been shown for spinal, brainstem, thalamic and thalamo-cortical lesions;^22,23 it is now reasonable to assert that if one central nervous system (CNS) lesion is able to induce a deficit in pain and temperature perception, it will also be able to alter the LEPs. In cases of dissociated sensory loss, LEPs are abnormal while conventional SEPs exploring the dorsal column–medial lemniscal system commonly remain within normal limits.^24–26 In general terms, there is a strict overlap between conditions that are able to decrease LEPs and those able to induce neuropathic pain.

On the basis of studies published so far, the European Federation of Neurological Societies (EFNS) has recommended the use of LEPs as an ancillary tool in the evaluation of neuropathic pain, and regrets that few university hospitals currently use this technique.²⁷ The main points relevant to the use of LEPs in the diagnosis and management of neuropathic pain are summarised below.