The role of dentate gyrus dopaminergic receptors in the lateral hypothalamic-induced antinociception during persistent inflammatory pain in male rats

Abstract

The lateral hypothalamus (LH) is one of the key brain areas involved in pain modulation. Also, the dentate gyrus (DG) of the hippocampus expresses various receptors, including dopaminergic receptors. Dopaminergic receptors play a key role in pain transmission and modulation within the brain. The present study aimed to investigate the involvement of DG dopaminergic receptors in the LH-induced antinociception during the presence of inflammatory pain. Male Wistar rats were used in this study. Cannulae were unilaterally implanted in their skull for microinjections into the LH and DG. The LH was chemically stimulated by carbachol injection (250\u2009nM/0.5\u2009µl saline). In separate groups, different doses (0.25, 1, and 4\u2009µg/0.5\u2009µl vehicle) of the D1- and D2-like dopamine receptor antagonists (SCH23390 and Sulpiride, respectively) were microinjected into the DG, 5\u2009min prior to intra-LH injection of carbachol. Five min after the second injection, formalin test as a persistent inflammatory pain model in animals was done in all rats. The results revealed that carbachol could induce antinociception following formalin injection into rat s hind paw. The 4\u2009µg dose of both antagonists significantly reduced the LH stimulation-induced antinociception in both phases of formalin pain responses. Although the 1\u2009µg dose of sulpiride significantly reduced antinociception during both phases, 1\u2009µg SCH23390 could only reduce this antinociception during the late phase. These findings demonstrate the involvement of DG dopaminergic receptors in the LH-induced antinociception. The results also suggest that the effectiveness of DG dopaminergic receptors is more pronounced during the late phase of formalin-induced pain responses.