Pathophysiology of neuropathic pain

Background: Neuropathic pain is notoriously difficult to manage properly, not only because of its varied nature and the absence of objective diagnostic tools but also because of extensive reciprocal neuronal interactive pathogenic mechanism from the molecular level to patient's own psychophysical characteristics. This paper briefly reviews the pathophysiology of neuropathic pain to the level of clinicians' interest and its potential in clinical practice Current Concepts: Recent research progress now allows us to obtain a bird view of neuropathic pain pathophysiology: peripheral and central sensitization. For peripheral sensitization, a local inflammatory milieu of the injured nerve primarily drives sequential phenotypic changes, which are critical and shared by both neuropathic and inflammatory pain. Central sensitization is led either by the hyperexcitability of the second-order afferent neuron itself or loss of physiological inhibitory control of the transmission of pain signal to the higher nervous system. Peripheral and central sensitization work synergistically but can also introduce neuropathic pain alone. Discussion and Conclusion: The cause of neuropathic pain is diverse, and understanding of its pathophysiology is still insufficient to realize a mechanism-based approach to clinical phenotypes or therapeutic applications. In dealing with chronic neuropathic pain, it is highly desirable to assess key aspects of a patient's pain based on a plausible mechanism and select the best management method accordingly.