Mechanisms of SensitizationCNS Changes

Many of the processes underlying central sensitization are analogous to those observed in the peripheral nervous system. For example, there is evidence that central sensitization reflects an increase in synaptic strength (analogous to transduction in the periphery), which reflects changes in the biophysical properties (144), density (145-148), and/or distribution of receptors critical to enabling postsynaptic neurons in the spinal cord dorsal horn (or at higher sites) to respond to excitatory input from nociceptive afferents. Similarly, there is evidence of changes in VGSCs (149) and VGPCs (150) associated with tissue injury, which mediate increases in the excitability of dorsal horn neurons. Interestingly, upregulation of a VGSC a subunit NaV1.3 occurs in both the spinal cord and the thalamus following spinal cord injury, where it appears to be critical for mediating sensitization of these CNS neurons (151). There is also evidence of phenotypic changes in CNS neurons following injury (110,152). As indicated above, the balance between inhibitory and excitatory input to CNS neurons is a critical factor influencing output. The importance of this balance is highlighted by the observation that pain associated with some forms of injury may reflect a loss of inhibition. A loss of inhibition may reflect a decrease in inhibitory receptors (153) as well as a structural change in the form of a loss of inhibitory interneurons (154).

There is also evidence for both segmental and suprasegmental changes in circuitry that appears to contribute to central sensitization, or at least increases in nociceptive processing following injury. For example, there is evidence for a segmental interaction between lumbosa-cral and thoracolumbar regions of the spinal cord, which may contribute to increases in the area of referred pain observed in the presence of inflammation of the colon (see Traub Chapter 7 this volume). The observation that pain associated with injury may reflect a shift in the balance of descending input to the spinal cord is an example of a change in suprasegmental circuitry; which a number of investigators have reported following injury, with a decrease in descending inhibition and/or an increase in descending facilitation (53).

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