Mu-opioid and D1-like dopamine receptor crosstalk in dorsal CA1 hippocampus modulates inflammatory pain in rats.

Chronic pain is one of the crucial medical problems worldwide. Recent advancements in neuroscience have highlighted the pivotal role of Mu (μ)-opioid receptors (MOR) and D1-like dopamine receptors (D1Rs) in modulating pain-related behaviors within the dorsal CA1 (dCA1) region of the hippocampus. This study investigated the hypothesis that MOR-D1R interactions in the dCA1 modulate inflammatory pain-related behaviors. A total of 159 adult male Wistar rats received unilateral microinjections of either drug solutions or vehicles. Separate groups were administered varying doses of the D1R agonist SKF38393 (3, 6, 12, and 24 mmol/0.5 μl) into the dCA1. In subsequent experiments, the D1R antagonist (SCH23390; 1.5, 3, 6, 12, or 24 mmol/0.5 μl) was microinjected into the dCA1 area of the hippocampus before injection of an effective dose of SKF38393 (12 mmol/0.5 μl) and morphine (10 mmol/0.5 μl). Finally, rats received the MOR antagonist naloxone (5, 15, and 45 mmol/0.5 μl) before SKF38393 (12 mmol/0.5 μl). Persistent inflammatory pain was assessed using the formalin test (50 µl of 2.5 % formalin) injected subcutaneously into the hind paw. Findings showed that administering SKF38393 into the dCA1 significantly reduced nociceptive responses. However, SCH23390 attenuated the antinociceptive effects of both SKF38393 and morphine. Similarly, naloxone significantly diminished SKF38393-induced pain relief. Results suggest that opioidergic and dopaminergic systems in the dCA1 interact to modulate pain relief. Cross-talk between D1Rs and MOR systems produces augmented analgesic effects, providing new insights for pain management research.