Role of the dentate gyrus of hippocampus on acute pain modulation: Investigating of dopaminergic-opioidergic interactions in pain-related behaviors in the tail-flick test.

Previous studies have shown that injections of opioid and dopamine agonists alone into the dentate gyrus (DG) increase the threshold for acute pain responses. Therefore, this study aimed to investigate whether the opioid and D1-like dopamine receptor (D1R) interact to modulate acute pain in DG. One hundred and forty-seven adult male Wistar rats were cannulated unilaterally in the DG. Separate groups of animals received different doses of SCH23390 (6, 12, and 24 mmol/0.5 μL), a D1R antagonist, before injection of an effective dose of morphine (25 mmol/0.5 μL). In another experiment, animals received different naloxone (5, 15, and 45 mmol/0.5 μL) dose, an opioid receptor antagonist, before administering the effective dose of SKF38393 (6 mmol/0.5 μL). Acute pain threshold was assessed using the tail-flick test. Behavioral data analysis indicated that blockade of D1R in the DG significantly attenuated morphine-induced antinociception (P < 0.001). Furthermore, the antinociceptive effects of SKF38393 were significantly reduced by blocking opioid receptors in the DG (P < 0.01). Interestingly, the effect of SCH23390 in reducing the antinociceptive effects of morphine (η2 = 0.65) was numerically higher than the effect of naloxone in reducing the antinociceptive effects of SKF38393 (η2 = 0.46). The results suggest a strong interaction between opioidergic and dopaminergic systems in the DG in modulating acute pain. These findings can be used to reveal the precise mechanisms of pain modulation in brain circuits and to develop new strategies in pain management with greater efficacy and fewer side effects.