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Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund's adjuvant-induced knee arthritis.
Robledo-González, L E; Martínez-Martínez, A; Vargas-Muñoz, V M; Acosta-González, R I; Plancarte-Sánchez, R; Anaya-Reyes, M; Fernández Del Valle-Laisequilla, C; Reyes-García, J G; Jiménez-Andrade, J M.
Afiliação
  • Robledo-González LE; Laboratorio de Farmacología.
  • Martínez-Martínez A; Laboratorio de Farmacología.
  • Vargas-Muñoz VM; Laboratorio de Farmacología.
  • Acosta-González RI; Departamento de Análisis Clínicos, Unidad Académica Multidisciplinaria Reynosa-Aztlán, UAT, Reynosa, Tamaulipas, Mexico.
  • Plancarte-Sánchez R; Departamento de Anestesiología, Terapia Intensiva y Clínica del Dolor, Instituto Nacional de Cancerología, Mexico City, Mexico.
  • Anaya-Reyes M; Investigación Clínica y Farmacovigilancia.
  • Fernández Del Valle-Laisequilla C; Investigación Clínica y Farmacovigilancia, Productos Medix, S.A. de C.V., Mexico City, Mexico.
  • Reyes-García JG; Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico.
  • Jiménez-Andrade JM; Laboratorio de Farmacología.
J Pain Res ; 10: 1777-1786, 2017.
Article em En | MEDLINE | ID: mdl-28794657
ABSTRACT

BACKGROUND:

The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund's adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined.

METHODS:

Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15-day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography.

RESULTS:

Acute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic and nonarthritic knee joints.

CONCLUSION:

Results suggest that mazindol via D2-like receptors has an antinociceptive role in mice with CFA-induced knee arthritis without modifying the bone health negatively.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Pain Res Ano de publicação: 2017 Tipo de documento: Article País de publicação: NEW ZEALAND / NOVA ZELÂNDIA / NUEVA ZELANDA / NZ

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Pain Res Ano de publicação: 2017 Tipo de documento: Article País de publicação: NEW ZEALAND / NOVA ZELÂNDIA / NUEVA ZELANDA / NZ