Analgesia and pain: Dual effect of dopamine on the peripheral nociceptive system is dependent on D2-or D1–like receptor activation

• Published in: European journal of pharmacology Vol. 922; p. 174872
• Main Authors: Queiroz, B.F.G., Fonseca, F.C.S., Ferreira, R.C.M., Romero, T.R.L., Perez, A.C., Duarte, I.D.G.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-05-2022
• Subjects: Antinociception; Dopamine; Dopaminergic receptors; Pain; Antinociception; Dopaminergic receptors; Dopamine; Pain
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2022.174872

In this study, a pharmacological approach, together with the paw pressure test, was used to investigate the role of dopamine and its receptors in the peripheral processing of the nociceptive response in mice. Initially, the administration of dopamine (5, 20, and 80 ng/paw) in the hind paw of male Swiss mice (30–40 g) promoted antinociceptive effects in a dose-dependent manner. This was considered a peripheral effect, as it did not produce changes in the nociceptive threshold of the contralateral paw. The D2, D3, and D4 dopamine receptor antagonists remoxipride (4 μg/paw), U99194 (16 μg/paw), and L-745,870 (16 μg/paw), respectively, reversed the dopamine-mediated antinociception in mice with PGE2-induced hyperalgesia. The D1 and D5 dopamine receptor antagonists SKF 83566 (2 μg/paw) and SCH 23390 (1.6 μg/paw), respectively, did not alter dopamine antinociception. In contrast, dopamine at higher doses (0.1, 1, and 10 μg/paw) caused hyperalgesia in the animals, and the D1 and D5 receptor antagonists reversed this pronociceptive effect (10 μg/paw), whereas the D2 receptor antagonist remoxipride did not. Our data suggest that dopamine has a dual effect that depends on the dose, as it causes peripheral antinociceptive effects at small doses via the activation of D2-like receptors and nociceptive effects at higher doses via the activation of D1-like receptors.
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