The neurobiology of central sensitization

Abstract

Objectives: This review discusses plasticity of excitatory synaptic transmission in the spinal dorsal horn and the role of this plasticity in contributing to the pathogenesis of pain hypersensitivity. Findings: In the dorsal horn pain transmission is mediated primarily through excitatory glutamatergic synapses. Glutamatergic synapses exhibit multiple forms of short-lasting and long-lasting forms of synaptic plasticity. The form of plasticity contributing to the persistent enhancement of pain transmission known as "central sensitization" is mechanistically similar to long-term potentiation in other regions of the central nervous system. This synaptic potentiation is produced by calcium entry through the N-methyl-D-aspartate subtype of glutamate receptor which initiates intracellular signalling cascades that ultimately cause an increase in the number and function of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate/kainate subtypes of glutamate receptors. Conclusions: Central sensitization is an expression of synaptic plasticity at glutamatergic synapses in pain transmission neurons in the dorsal horn. The resultant enhancement of synaptic responses increases the gain in pain pathways and contributes in a significant manner to the pain hypersensitivity. © 2002 by The Haworth Press, Inc. All rights reserved.