Nucleus accumbens dopaminergic neurotransmission switches its modulatory action in chronification of inflammatory hyperalgesia.

Abstract

Dopaminergic neurotransmission in the nucleus accumbens, a central component of the mesolimbic system, has been associated with acute pain modulation. As there is a transition from acute to chronic pain ('chronification'), modulatory structures may be involved in chronic pain development. Thus, this study aimed to elucidate the role of nucleus accumbens dopaminergic neurotransmission in chronification of pain. We used a rat model in which daily subcutaneous injection of prostaglandin E2 in the hindpaw for 14days induces a long-lasting state of nociceptor sensitization that lasts for at least 30days following the end of the treatment. Our findings demonstrated that the increase of dopamine in the nucleus accumbens by local administration of GBR12909 (0.5nmol/0.25μL), a dopamine reuptake inhibitor, blocked prostaglandin E2 -induced acute hyperalgesia. This blockade was prevented by a dopamine D2 receptor antagonist (raclopride, 10nmol/0.25μL) but not changed by a D1 receptor antagonist (SCH23390, 0.5, 3 or 10nmol/0.25μL), both co-administered with GBR12909 in the nucleus accumbens. In contrast, the induction of persistent hyperalgesia was facilitated by continuous infusion of GBR12909 in the nucleus accumbens (0.021nmol/0.5μL/h) over 7days of prostaglandin E2 treatment. The development of persistent hyperalgesia was impaired by SCH23390 (0.125nmol/0.5μL/h) and raclopride (0.416nmol/0.5μL/h), both administered continuously in the nucleus accumbens over 7days. Taken together, our data suggest that the chronification of pain involves the plasticity of dopaminergic neurotransmission in the nucleus accumbens, which switches its modulatory role from antinociceptive to pronociceptive.