The functional role of opioidergic system within the ventral tegmental area and the dentate gyrus of hippocampus in modulation of the persistent inflammatory pain in the rats

The ventral tegmental area (VTA) and hippocampus are implicated in various brain functions, including pain modulation. However, the precise involvement of their opioidergic system in this process has not yet been fully elucidated. The current study investigated the role of opioid receptors in the VTA and dentate gyrus (DG) region of the hippocampus on inflammatory pain-related behaviors. One hundred fifty-three adult albino Wistar rats (200-250 g) underwent stereotaxic surgery for unilateral cannula implantation into either the VTA or DG. Following recovery, the formalin test was used to evaluate inflammatory pain after drug or vehicle microinjections into the VTA or DG. In the first set of experiments, animals received intra-VTA or intra-DG morphine, a μ-opioid receptor (MOR) agonist, at different doses, and pain responses were measured. In the second set, various doses of naloxone, a non-selective opioid receptor antagonist, were administered prior to the effective dose of morphine identified in the first set. Results indicated that morphine reduced nociceptive responses in both phases of the formalin test, with a lower effective dose required in the VTA (10 mmol in the VTA; 50 mmol in the DG). In contrast, naloxone pretreatment attenuated morphine-induced analgesia, with lower doses observed in the DG. In summary, these findings underscore region-specific differences in MOR-mediated analgesia between the VTA and DG, suggesting that distinct cellular and neural circuit mechanisms may contribute to opioid-induced modulation of inflammatory pain.