Alteration of neuronal activity after digit amputation in rat anterior cingulate cortex

Phantom limb pain is experienced by nearly 50 - 80% of the patients following limb amputation. The anterior cingulate cortex (ACC) is a part of the limbic system that is an essential component in mediating the affective and emotional component of pain responses. To explore the role of ACC in the phantom limb pain, we recorded evoked excitatory postsynaptic potentials (EPSPs), cortical network activity and electrophysiological properties of pyramid neurons in adult rat ACC before and after a third hind paw digit amputation using in vivo intracellular or extracellular recording and staining techniques. The recorded neurons were morphologically identified as pyramidal neurons in the ACC region. The spontaneous activity of ACC neurons significantly reduced with a more percentage of down state after amputation, this is correlated with a decrease in spontaneous spikes in medial thalamus. However, the amplitude of the evoked EPSPs was increased significantly shortly after amputation and lasted for up to 7 days. This potentiation is associated with an increase of paired-pulse facilitation (PPF), suggesting the involvement of presynaptic component in this process. No significant difference in membrane properties was observed after amputation. On the other hand, administration of Complete Freund's Adjuvant (CFA) into the hind paw, a model of inflammatory pain, induced the potentiation of EPSPs in ACC neurons at 7 days after injection. These results demonstrate that digit amputation induced a long-lasting potentiation of synaptic transmission and decrease of cortical network activity in ACC in rats, which might contribute to the phantom limb pain.