D1-and D2-like dopamine receptors within the nucleus accumbens contribute to stress-induced analgesia in formalin-related pain behaviours in rats

BackgroundStressful experiences can produce analgesia, termed stress-induced analgesia (SIA). Meanwhile, it has been widely established that the mesolimbic dopamine pathway and nucleus accumbens (NAc) have a profound role in pain modulation. In this study, we examined the role of accumbal dopamine receptors in antinociception caused by forced swim stress (FSS) in order to understand more about the function of these receptors within the NAc in FSS-induced analgesia. MethodStereotaxic surgery was unilaterally performed on adult male Wistar rats weighing 230-250g (some on the left and some on the right side of the midline). Two supergroups were microinjected into the NAc with a D1-like dopamine receptor antagonist, SCH-23390, at doses of 0.25, 1 and 4g/0.5l saline per rat or Sulpiride as a D2-like dopamine receptor antagonist at the same doses [0.25, 1 and 4g/0.5l dimethyl sulfoxide (DMSO) per rat]; while their controls just received intra-accumbal saline or DMSO at 0.5l, respectively. The formalin test was performed after rats were subjected to FSS (6min, 251 degrees C) to assess pain-related behaviours. ResultsThe results demonstrated that intra-accumbal infusions of SCH-23390 and Sulpiride dose-dependently reduced FSS-induced antinociception in both phases of the formalin test. However, the percentage decrease in area under the curve (AUC) values calculated for treatment groups compared to formalin-control group was more significant in the late phase than the early phase. ConclusionOur findings suggest that D1- and D2-like dopamine receptors in the NAc are involved in stress-induced antinociceptive behaviours in the formalin test as an animal model of persistent inflammatory pain. What does this study add Forced swim stress (FSS) induces the antinociception in both phases of formalin test. Blockade of accumbal dopamine receptors attenuate the antinociception induced by FSS. Stress-induced analgesia is dose-dependently reduced by dopamine receptor antagonists in both phases, although it is more prominent during the late phase.