The anterior cingulate cortex (ACC) plays a key role in pain processing. It has been reported that increased activity of glutamatergic projections into the ACC intensifies nociception; whereas dopaminergic projections inhibit it. The aim of this study was to evaluate the role of dopaminergic and NMDA systems of the ACC in the modulation of long-term nociception elicited by sciatic denervation in the rat. Score, onset and incidence of long-term nociception were measured by the autotomy behavior. The effects of a single microinjection into the ACC of different doses of dopamine (100 nM, 100 microM and 100 mM), a NMDA receptor antagonist (MK801 200 nM and 9.34 mM) and amantadine, a dopamine agonist and NMDA receptor antagonist (10, 100 and 1000 microM) were tested on long-term nociception. Dopamine diminished autotomy behavior in an inverse dose-dependent manner, with dopamine 100 nM as most effective concentration. MK801 and amantadine elicited a significant reduction on autotomy score. Prior injections of D1 and D2 receptor antagonists blocked the antinociceptive effects of amantadine on long-term nociceptive behavior. The present study suggests an interaction between dopaminergic and glutamatergic systems within the ACC in the genesis and maintenance of long-term nociception.

The rostral agranular insular cortex (RAIC) receives dopaminergic projections from the mesolimbic system, which has been involved in the modulation of nociceptive processes. In this study we determined the contribution of dopamine D(1) and D(2) receptors in the RAIC regarding nociception processing in a neuropathic pain model, as well as inflammatory articular nociception measured as pain-induced functional impairment in the rat (PIFIR). Microinjection of vehicle or substances into the RAIC was performed after the induction of nociception. The groups were treated with: a dopamine D(1) receptor antagonist (SCH-23390), a dopamine D(1) receptor agonist (SKF-38393), a dopamine D(2) receptor agonist (TNPA) and a dopamine D(2) receptor antagonist (spiperone). Chronic nociception, induced by denervation, was measured by the autotomy score in which onset and incidence were also determined. The SCH-23390 and TNPA groups showed a decrease in the autotomy score and a delay on the onset as compared to control, whereas the PIFIR groups did not show statistical differences. This work shows the differential role of dopamine receptors within the RAIC in which the activation of D(2) or the blockade of D(1) receptors elicit antinociception.