中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (2): 450-458.doi: 10.4103/1673-5374.317984

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

多巴胺能D3/D2受体首选激动剂普拉克索可减轻利血平诱导的纤维肌痛

  

  • 出版日期:2022-02-15 发布日期:2021-10-08

Pramipexole, a dopamine D3/D2 receptor-preferring agonist, attenuates reserpine-induced fibromyalgia-like model in mice

Carlos Pereira Martins1, 2, Rodrigo Sebben Paes1, Gabriela Mantovani Baldasso1, Eduarda Gomes Ferrarini1, 2, Rahisa Scussel3, Rubya Pereira Zaccaron3, Ricardo Andrez Machado-de-Ávila3, Paulo Cesar Lock Silveira3, Rafael Cypriano Dutra1, 2, *   

  1. 1Laboratory of Autoimmunity and Immunopharmacology, Department of Health Sciences, Campus Araranguá, Universidade Federal de Santa Catarina, Araranguá, SC, Brazil; 2Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; 3Laboratory of Experimental Physiopathology, Program of Postgraduate in Science of Health, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
  • Online:2022-02-15 Published:2021-10-08
  • Contact: Rafael Cypriano Dutra, PhD, rafaelcdutra@gmail.com or rafael.dutra@ufsc.br.
  • Supported by:
    This project was supported by grants from Programa de Pós-graduação em Neurociências (PGN), Programa INCT-INOVAMED (grant No. 465430/2014-7), Fundação de Apoio à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), all from Brazil. CPM was recipient of a master fellowship from CAPES–Brazil; RSP and GMB were undergraduate students in Physiotherapy receiving grants from CNPq; EGF and RS were recipient of a PhD fellowship from CAPES–Brazil; RAMA, PCLS and RCD are recipients of a research productivity fellowship from the CNPq.

PDF

134

摘要：

纤维肌痛(FM)表现为持续的感觉减退，包括躯体和情绪功能障碍、抑郁和焦虑；虽然FM的病因尚不清楚，但生物胺的显著减少是其重要的发病机制。为了解多巴胺能D3/D2受体在纤维肌痛过程中的作用，实验建立了利血平诱导纤维肌痛小鼠模型，然后对该模型小鼠进行腹腔注射多巴胺能D3/D2受体激动剂普拉克索。结果显示，普拉克索（PPX）可抑制利血平引起的机械性痛觉和热敏感性升高，表现为普拉克索减少了模型小鼠强迫游泳试验和溅水试验中的不动时间和增加了梳理次数；且接受普拉克索可减轻模型小鼠焦虑状态，表现为其在高架十字迷宫开放臂中停留的时间延长。普拉克索还可恢复利血平下调的额叶皮质和脊髓组织的多巴胺水平。普拉克索治疗可抑制脊髓组织氧化剂DCFH(2′,7′-二氯二氢荧光素)和亚硝酸盐的产生，并上调超氧化物歧化酶的活性。实验结果表明，多巴胺能D3/D2受体激动剂能够减轻纤维肌痛模型小鼠的疼痛和情绪功能障碍，其途径可能涉及恢复复中枢神经系统抗氧化能力。

https://orcid.org/0000-0002-6938-2161 (Rafael Cypriano Dutra)

Abstract: Fibromyalgia (FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole (PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plus-maze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. Reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH (2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage (carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina (UFSC) Ethics Committee (approval No. 2572210218) on May 10, 2018.

Key words: dopamine, dopaminergic system, fibromyalgia, hyperalgesia, pain, pramipexole, reserpine

中图分类号: