The D2-like dopamine and opioidergic receptors have interactions in the CA1 region of the hippocampus in modulating the formalin-induced inflammatory pain.

Recent evidence highlights the CA1 region of the hippocampus's role in modulating nociceptive responses, with a well-established opioid (OP) system and a high density of dopamine receptors (D2Rs). However, interactions between these systems in response to noxious stimuli are underexplored. This study aimed to investigate the OP and D2Rs' interactions in CA1 using an animal model of inflammatory pain. After implanting a cannula in the scalp, male rats were received varying doses of Quinpirole (4, 8, 16, and 32 mmol/0.5 μl Saline) as a D2 receptor agonist in the CA1 region. Subsequently, Sulpiride (1.5, 3, 6 mmol/0.25 μl 12 % DMSO) was microinjected as a D2 antagonist before the effective Quinpirole dose (32 mmol/0.25 μl Saline). Naloxone (1.5, 5, and 15 mmol/0.25 μl Saline) was used as an OP antagonist to study OP and DA interactions. In other experiments, Sulpiride (1.5, 3, 6, 12 mmol/0.25 μl 12 % DMSO) preceded Morphine (25 mmol/0.25 μl Saline). The formalin test involved a 50 μl subcutaneous injection of 2.5 % formalin into the rat's hind paw to induce pain. The main findings indicated that the OP and DA systems in the CA1 region of the hippocampus interact to produce anti-nociceptive responses. Specifically, Quinpirole injections triggered analgesic responses, which were diminished by Sulpiride. Naloxone blocked the pain-relieving effects of Quinpirole, while Sulpiride reduced Morphine's analgesic responses in the CA1 region. These results suggest that understanding these interactions can help develop new medications to improve pain management and reduce risks associated with current opioid treatments.