The dopaminergic and opioidergic interactions in the nucleus accumbens in the suppression of pain affect: Exploring their impact on formalin-induced pain in rats

Recent studies suggest that the nucleus accumbens (NAc) may influence the brain's response to pain signals, indicating a role beyond motivation and reward. The study delved into how the D1-like dopamine receptors (D1Rs) and μ-opioid receptors (MOR) interact in the NAc region in the context of formalin-induced pain. Rats received intra-accumbal various doses of morphine as an MOR agonist (5, 10, 25, and 50 mmol/0.5μl) and different doses of SKF38393 as a selective D1Rs agonist (1.5, 3, 6, and 12 mmol/0.5μl) in separate experimental groups, respectively. In the second stage, animals received different doses of SCH23390 as a selective D1Rs antagonist (1.5, 3, 6, and 12 mmol) before an effective dose of SKF38393 (6 mmol) and morphine (10 mmol). The rats were then given naloxone as an MOR antagonist (1.5, 5, and 15 mmol) before being given an effective dose of SKF38393 (6 mmol). In the formalin test, 50 µl formalin (2.5 %) was subcutaneously injected into the rat's hind paw to induce pain behavioral responses. The main findings indicated that the opioidergic and dopaminergic systems in the NAc region interact to create analgesic effects. The injection of morphine and SKF38393 into the NAc resulted in pain-relieving impacts. However, SCH23390 decreased the antinociceptive impacts of SKF38393 and morphine. Similarly, naloxone reduced the analgesic effects of SKF38393. The interactions between D1Rs and MOR can lead to synergistic effects. Therefore, using D1Rs agonists along with morphine can enhance the antinociceptive effect of morphine while reducing its side effects.