Intra-accumbal dopaminergic system modulates the restraint stress-induced antinociceptive behaviours in persistent inflammatory pain.

Abstract

Stress activates several neural pathways that inhibit pain sensation. Nucleus accumbens (NAc), as an important component of the mesolimbic dopaminergic system, has a major role in pain modulation and is differentially affected by stress. Based on the nature of stressors, the direction of this effect is controversial. We previously showed that forced swim stress-induced analgesia through activation of NAc dopamine receptors. In this study, we aimed to examine the role of dopamine receptors within the NAc in restraint stress (RS)-induced analgesia. Male Wistar rats weighing 230-250g were unilaterally implanted with a cannula into the NAc. D1-like dopamine receptor antagonist, SCH-23390 (0.25, 1 and 4µg/0.5µL saline), or D2-like dopamine receptor antagonist, Sulpiride (0.25, 1 and 4µg/0.5µl DMSO), were microinjected into NAc in two separate super groups 5min prior to exposure to RS. Their control groups just received intra-accumbal saline or DMSO (0.5µl) respectively. The formalin test was performed after animals were subjected to RS using Plexiglas tubes. The results demonstrated that RS produces analgesia in both phases of the formalin test. Intra-NAc injection of SCH-23390 equally reduced RS-induced analgesia in both early and late phases of the formalin test, while Sulpiride reduced RS-induced analgesia just at the late phase. These findings suggest that the dopaminergic system might act as a potential endogenous pain control system in stress conditions. However, the lack of evaluation of the role of the dopaminergic system in RS-induced antinociception in acute pain conditions is considered as a limitation for this study. In addition, a comprehensive evaluation of this endogenous pain control system in animal and clinical studies will guide future efforts for developing more effective medication. Restraint stress (RS) induces the antinociceptive behaviors in both phases of formalin test. Blockade of intra-accumbal dopamine receptors impresses the antinociception induced by RS. Blockade of D1-like dopamine receptor equally reduced RS-induced analgesia in both early and late phases of the formalin test. Blockade of D2-like dopamine receptor reduced RS-induced analgesia just at the late phase.