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

• Published in: The European journal of neuroscience 2015-10, Vol.42 (7), p.2380-2389
• Main Authors: Dias, Elayne Vieira, Sartori, César Renato, Marião, Paula Ramos, Vieira, André Schwambach, Camargo, Lilian Calili, Athie, Maria Carolina Pedro, Pagliusi, Marco Oreste, Tambeli, Claudia Herrera, Parada, Carlos Amilcar
• Format: Article
• Language: English
• Subjects: Animals; Benzazepines - administration & dosage; Benzazepines - pharmacology; Chronic Pain - metabolism; Disease Models, Animal; Dopamine - metabolism; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - pharmacology; Dopamine D2 Receptor Antagonists - administration & dosage; Dopamine D2 Receptor Antagonists - pharmacology; dopamine receptors; Dopamine Uptake Inhibitors - administration & dosage; Dopamine Uptake Inhibitors - pharmacology; Hyperalgesia - chemically induced; Hyperalgesia - metabolism; Male; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; pain chronification; persistent hyperalgesia; Piperazines - administration & dosage; Piperazines - pharmacology; rat; Rats; Rats, Wistar; Receptors, Dopamine D1 - antagonists & inhibitors
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.13015

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 14 days induces a long‐lasting state of nociceptor sensitization that lasts for at least 30 days following the end of the treatment. Our findings demonstrated that the increase of dopamine in the nucleus accumbens by local administration of GBR12909 (0.5 nmol/0.25 μL), a dopamine reuptake inhibitor, blocked prostaglandin E2‐induced acute hyperalgesia. This blockade was prevented by a dopamine D2 receptor antagonist (raclopride, 10 nmol/0.25 μL) but not changed by a D1 receptor antagonist (SCH23390, 0.5, 3 or 10 nmol/0.25 μL), 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 (0.021 nmol/0.5 μL/h) over 7 days of prostaglandin E2 treatment. The development of persistent hyperalgesia was impaired by SCH23390 (0.125 nmol/0.5 μL/h) and raclopride (0.416 nmol/0.5 μL/h), both administered continuously in the nucleus accumbens over 7 days. 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. Nucleus Accumbens (NAc) has been associated with pain modulation. Dopamine increase in the NAc blocks acute inflammatory hyperalgesia. This effect is mediated by dopamine D2 but not by D1 receptor. In contrast, the induction of persistent hyperalgesia is facilitated by persistent increase of dopamine in the NAc and dependent on dopamine D1 and D2 receptors. NAc dopaminergic neurotransmission is involved in the chronification of hyperalgesia and its modulatory role switches in the transition from acute to chronic condition, changing from anti to pro‐hyperalgesic.