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The ability to modulate pain perception is as critical to survival as pain itself. The most known pain modulation pathway is the PAG–RVM (periaqueductal gray–rostral ventromedial medulla) descending system. In this study, we hypothesized that it is functionally linked to the ascending nociceptive control, which is a form of pain-induced analgesia dependent on mesolimbic mechanisms. To test this hypothesis, we used a pharmacological approach, in which the antinociception induced by noxious stimulation (forepaw injection of capsaicin) was detected in a standard rat model of inflammatory pain (hindpaw injection of carrageenan). This antinociception was blocked by interventions known to block the ascending nociceptive control-mediated analgesia: the blockade of μ-opioid (Cys²,Tyr³,Orn⁵,Pen⁷amide (CTOP) 0.5 μg) or of dopamine (SCH23390 1.8 μg and raclopride 5 μg) receptors within the NAc (nucleus …