Repetitive C afferent input evokes a facilitated state of processing that results in increased receptive fields and exaggerated responses to afferent input ("wind-up"). These phenomena underlie the behavioral phenomena of secondary hyperalgesia and this in turn is an important component of postoperative pain. The initiation of this facilitated component is not well blocked by even higher concentrations of volatile anesthetics, but it can be prevented by pretreatment with agents known to block afferent input (local anesthetics) or C-fiber transmitter release (opiates) or to act at one of several links to block a complex spinal cascade involving the N-methyl-D-aspartate receptor, nitric oxide synthase, and cyclooxygenase. These fundamental mechanisms promise to have an impact on the management of postoperative pain.