Secondary hyperalgesia and presynaptic inhibition: an update.

One of the most prominent features of secondary hyperalgesia is touch-evoked pain, i.e., pain evoked by dynamic tactile stimuli applied to areas adjacent or remote from the originating injury. It is generally accepted that the neurobiological mechanism of this sensory alteration involves the central nervous system (CNS) so that incoming impulses in low-threshold mechanoreceptors from the area of secondary hyperalgesia can evoke painful sensations instead of touch. Some years ago we proposed a mechanistic model for this form of pain based on presynaptic interactions in the spinal dorsal horn between the terminals of low-threshold mechanoreceptors and of nociceptors. Here we review the evidence gathered in support of this model in the intervening years with special reference to experimental studies of antidromic activity (Dorsal Root Reflexes--DRRs) in nociceptive afferents and on the acquisition of low-threshold inputs by nociceptor-specific neurons in the spinal dorsal horn. We also discuss and identify potential molecular mechanisms that may underlie the presynaptic interaction model and therefore that could be responsible for the development of secondary hyperalgesia.