What’s behind neuropathic pain? Neurophysiological diagnostic tests investigating mechanisms underlying neuropathic pain

Mechanisms Underlying Neuropathic Pain • Electrophysiological recordings demonstrate that the regenerating C-fibers of damaged axons develop ongoing spontaneous activity, abnormal excitability and an increased sensitivity to chemical, thermal and mechanical stimuli. This phenomenon is termed peripheral sensitization. • Following nerve damage, as a consequence of the peripheral sensitization, second order nociceptive neurons develop an increased background activity, enlarged receptive field and increased responses to all afferent impulses. This phenomenon is termed central sensitization. Mechanism-based Symptoms • Neuropathic pain may be ongoing (e.g., burning pain), paroxysmal (e.g., electrical shock-like sensations) or provoked by various stimuli. The different types of neuropathic pain probably arise through variations in the underlying mechanisms. • Burning pain probably reflects the abnormal, spontaneous activity originating in damaged nociceptive fiber axons. • Paroxysmal pain may be related to high-frequency bursts generated in demyelinated Aβ-fibers. • Allodynia may be due to a peripheral mechanism, reflecting an abnormal reduction of the mechanical threshold in sensitised nociceptors, or to a central mechanism, reflecting the sensitization of central nociceptive neurons to mechanically evoked input. • Successful neuropathic pain management requires the definition of precise sensory profiles. The diagnostic process should aim at finding specific sensory profiles through clinical examination, questionnaires dedicated to neuropathic pain and laboratory tools. • A classification per sensory profile rather than etiology might minimize pathophysiological heterogeneity and increase the power to detect a positive treatment result. Genetic Inheritance of Neuropathic Pain • Reasonably, the genetic risk of developing neuropathic pain after nervous system damage results from multiple risk- conferring genes.