title: 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 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.
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: Elayne Vieira
authors.initials: EV
authors.lastname: Dias
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: César Renato
authors.initials: CR
authors.lastname: Sartori
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: Paula Ramos
authors.initials: PR
authors.lastname: Marião
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: André Schwambach
authors.initials: AS
authors.lastname: Vieira
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: Lilian Calili
authors.initials: LC
authors.lastname: Camargo
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: Maria Carolina Pedro
authors.initials: MC
authors.lastname: Athie
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: Marco Oreste
authors.initials: MO
authors.lastname: Pagliusi
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: Claudia Herrera
authors.initials: CH
authors.lastname: Tambeli
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, Rua Monteiro Lobato, 255, Cidade Universitaria Zeferino Vaz, Box 6109, 13083-865, Campinas, SP, Brazil.
authors.forename: Carlos Amilcar
authors.initials: CA
authors.lastname: Parada
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D059350:Chronic Pain / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors
chemical_list: C461261:(1-(2-(bis(4-fluorophenyl)methoxy)ethyl)-4-(3-hydroxy-3-phenylpropyl) piperazinyl decanoate); D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D004298:Dopamine
keywords: dopamine receptors; pain chronification; persistent hyperalgesia; rat