Glutamate receptor response properties of nociceptive synapses on NK1R⁺ positive lamina I neurons were determined three days after induction of chronic peripheral inflammation with Freund’s Complete Adjuvant (CFA). A significant increase in the AMPAR/NMDAR ratio was found during inflammation, which was associated with a significant reduction in the quantal amplitude of NMDAR-mediated synaptic currents. A significant shortening of the quantal AMPA current decay, a greater inward rectification of the AMPAR mediated eEPSC amplitude and an increased sensitivity to the Ca²⁺ permeable AMPAR channel blocker 1-naphthylacetyl spermine (NAS) was also observed, indicating an increase in the contribution of Ca²⁺ permeable AMPARs at this synapse during inflammation. Furthermore the reduced effectiveness of NR2B specific antagonist CP-101,606 on NMDAR-mediated eEPSCs together with a decrease in Mg²⁺ sensitivity suggests a down regulation of the highly Mg²⁺ sensitive and high conductance NR2B subunit at this synapse. These changes in glutamatergic receptor function during inflammation support the selective effectiveness of Ca²⁺ permeable AMPAR antagonists in inflammatory pain models and may underlie the reported ineffectiveness of NR2B antagonists in spinal antinociception.