Clinical neurophysiology of neuropathic pain

Timely and accurate diagnosis of neuropathic pain is critical for optimizing therapeutic outcomes and minimizing treatment delays. According to current standards, the diagnosis of definite neuropathic pain requires objective confirmation of a lesion or disease affecting the somatosensory nervous system. This can be provided by specialized neurophysiological techniques as conventional methods like nerve conduction studies and somatosensory evoked potentials may not be sufficient as they do not assess pain pathways. These specialized techniques apply various stimuli, such as thermal, electrical, or mechanical, alongside assessments of spinal/cortical potential or electromyographic reflex recordings. The selection of techniques is guided by the patient's clinical history and examination. The most common neurophysiological tests used in clinical practice are pain-related evoked potentials (PREPs) providing an objective evaluation of nociceptive pathways. Four types of PREPs are employed: laser evoked potentials, contact-heat evoked potentials, intra-epidermal electrical stimulation evoked potentials, and pinprick evoked potentials, with the two former ones being the most robust and reliable ones. These techniques investigate small-diameter fibers, primarily Aδ-fibers, and spinothalamic tracts allowing the identification of peripheral or central nervous system lesions. Yet, they are limited in capturing neuronal mechanisms underlying neuropathic pain or in providing objective quantification of pain sensation. Two neurophysiological measures which investigate the pain system beyond its integrity are the nociceptive withdrawal reflex and the N13 component of somatosensory evoked potentials. Both of these methods are more commonly used in research than clinical practice, but they pose interesting approaches to quantify central sensitization, a key underlying mechanism of neuropathic pain. Future investigations in neuropathic pain are therefore warranted.