Synaptic mechanisms of hyperalgesia.

Introduction ?#1 Hyperalgesia and allodynia often aggravate pain for variable periods of time after trauma, surgery or inflammation. Pain that is induced by normally nonpainful stimuli (allodynia) or abnormally intense pain elicited by noxious stimuli (hyperalgesia) may be the consequence of an increased sensitivity of nociceptors (peripheral sensitization) or may be due to an increased responsiveness of neurons in the central nervous system (central sensitization). The sensitization of nociceptors is typically limited in time to the period of primary injury. Central sensitization may, however, outlast the period of noxious input to the central nervous system by hours to weeks and in some unfortunate patients the period of abnormal pain sensitivity may last even longer. The long-lasting hyperalgesia that may remain after healing of the primary injury is often difficult to treat and to prevent. Consequently much research effort has been devoted to better understand the neurobiological mechanisms underlying persistent pain and hyperalgesia (see Woolf and Mannion, 1999; Yaksh et al., 1999 for reviews). The peripheral mechanisms of hyperalgesia are discussed in other chapters of this volume. Here, we will focus on central mechanisms. Four principle mechanisms of afferent-induced central sensitization can be proposed: