Immunostaining for GluR1 and GluR2/3 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is prominent in laminae I and II of the normal dorsal horn, with much less staining in deeper laminae. Three days after dorsal rhizotomy, image analysis demonstrates a significant decrease in staining density for both antibodies in the superficial dorsal horn. By contrast, staining density is significantly increased in laminae III, IV and the reticulated region of lamina V for GluR1 only. This increase suggests that AMPA receptors contribute to deafferentation or radicular pain by at least two mechanisms: (1) up-regulation of GluR1 subunits of the AMPA receptor in deeper laminae, and (2) enhanced Ca2+ permeability of dorsal horn neurons because AMPA receptors lacking the GluR2 subunit are Ca2+ permeable. Glutamate activation of these receptors could initiate or potentiate second messenger cascades that could well contribute to neuronal changes documented in the dorsal horn of deafferented animals.