Pathophysiology of pain.

The processing and interpretation of pain signals is a complex process that entails excitation of peripheral nerves, local interactions within the spinal dorsal horn, and the activation of ascending and descending circuits that comprise a loop from the spinal cord to supraspinal structures and finally exciting nociceptive inputs at the spinal level. Although the "circuits" described here appear to be part of normal pain processing, the system demonstrates a remarkable ability to undergo neuroplastic transformations when nociceptive inputs are extended over time, and such adaptations function as a pronociceptive positive feedback loop. Manipulations directed to disrupt any of the nodes of this pain facilitatory loop may effectively disrupt the maintenance of the sensitized pain state and diminish or abolish neuropathic pain. Understanding the ascending and descending pain facilitatory circuits may provide for the design of rational therapies that do not interfere with normal sensory processing.