Increased synaptic GluR1 subunits in the anterior cingulate cortex of rats with peripheral inflammation.

Adaptation of glutamatergic transmission, including the trafficking of AMPA receptor subunits, serves as an important mechanism underlying long-term neuronal plasticity under several pathophysiological conditions, including pain. Meanwhile, the anterior cingulate cortex (ACC) is found to be critically involved in the central processing and modulation of noxious stimulus, although the neuroadaptation in the ACC has not yet been well established in the setting of chronic pain. To address these issues, the present work was undertaken to explore the adaptation of glutamatergic AMPA receptor subunits in ACC neurons in rats with inflammation in the left hindpaw induced with Complete Freund's Adjuvant (CFA). The results showed an increased AMPA receptor-mediated glutamatergic evoked EPSC in the ACC neurons, indicating an enhanced basal glutamatergic transmission. Furthermore, an increased distribution of the synaptic GluR1 subunit was observed in the ACC neurons. We conclude that chronic peripheral inflammation significantly enhances the synaptic insertion of GluR1 subunits in the ACC neurons, which consequently increases the central excitatory transmission during chronic pain. This investigation may clarify, at least partially, the underlying supraspinal mechanism for adaptation of glutamatergic transmission during chronic pain induced by peripheral inflammation.