Reciprocal blockade of the opioid and D2-like dopamine receptors in the nucleus accumbens modulates the pain-related behaviors in an animal model of inflammatory pain

Studies showed that dopamine and opioid systems in the brain have essential role in the modulation of pain perception. The evidence indicated that in the nucleus accumbens (NAc), both dopamine type 2 (D2) receptors and opioid receptors are highly expressed. However, the interaction of these systems in NAc was not investigated in the modulation of inflammatory pain. One hundred twenty-six adult male Wistar rats received unilateral microinjections of different doses of morphine (2.5, 5, 10, and 25 mmol/0.5 μl) and quinpirole (8, 16, and 32 mmol/0.5 μl) to assess their effects as opioid and D2-like receptor agonists in the NAc. In the next step, the rats were administered varying doses of sulpiride (3, 6, 12, and 24 mmol/0.5 μl), a D2-like receptor antagonist, before an effective dose of quinpirole (32 mmol/0.5 μl). They also received naloxone (1.5, 5, and 15 mmol/0.5 μl) before the same effective dose of quinpirole (32 mmol/0.5 μl). The formalin test was employed to evaluate their inflammatory pain thresholds. Results indicated that intra-accumbal administration of morphine- and quinpirole-induced antinociceptive responses. However, sulpiride significantly diminished these responses. Naloxone also reduced the quinpirole’s antinociceptive effects. Interestingly, sulpiride was less effective in reversing the analgesic effects of morphine ( η 2 = 0.17 in the first phase and η 2 = 0.37 in the late phase) than naloxone in reversing the quinpirole’s analgesic effects ( η 2 = 0.4 in the first phase and η 2 = 0.53 in the late phase). These findings suggest an interaction between the opioidergic and dopaminergic systems in pain relief.