Wind-up and the NMDA receptor complex from a clinical perspective

More rational treatment of chronic pain depends on increased understanding of the pathophysiological mechanisms underlying the various symptoms and characteristics of chronic pain. Central sensitization of pain represents an important pathophysiological mechanism that has received great attention in recent years. The experimental models used to explore mechanisms of central sensitization include the study of wind-up in animals and temporal summation of pain in humans. Wind-up was described more than 30 years ago as progressively increasing activity in dorsal horn cells following repetitive activation of primary afferent C-fibres. In humans, temporal summation of repeated painful stimuli has been regarded as a psychophysical correlate of wind-up. This review focuses on the relationship between wind-up, temporal summation and central sensitization. In particular, the role of NMDA receptor mechanisms in the modulation of wind-up/temporal summation is discussed. The data presented here indicate that the study of wind-up and temporal summation has given information about some of the complex mechanisms underlying central sensitization. Both wind-up and temporal summation appear to be dependent on NMDA receptor activation. The results of clinical trials in patients with chronic pain suggest that the NMDA receptor may represent a new target for modulation of abnormal temporal summation of pain, as well as other characteristics of chronic pain.