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There is now increasing evidence that pathological pain states are at least in part driven by changes in the brain itself. Descending modulatory pathways are known to mediate top-down regulation of nociceptive processing, transmitting cortical and limbic influences to the dorsal horn. However, these modulatory pathways are also intimately intertwined with ascending transmission pathways through positive and negative feedback loops. Models of persistent pain that fail to include descending modulatory pathways are thus incomplete. Although teasing out individual links in a recurrent network is never straightforward, it is imperative that understanding of pain modulation be fully integrated into how we think about pain.

Since a detailed review of the organization of the primary afferent input to the dorsal horn has recently been published (1), the purpose of my discussion will be to highlight three areas in which considerable new information is available about pain processing and pain control mechanisms. Specifically, I will discuss some new perspectives on the problem of the processing of the afferent input at the level of the dorsal horn, mechanisms of opioid regulation of nociceptive processing and new studies of the factors that contribute to the development of opiate tolerance.