Funding/support information: This work was supported by a PROMEP grant (103.5/12/3430, incorporation of new full time professors).
Early, Middle, or Late Administration of Zoledronate Alleviates Spontaneous Nociceptive Behavior and Restores Functional Outcomes in a Mouse Model of CFA-Induced Arthritis
Article first published online: 9 JUL 2014
© 2014 Wiley Periodicals, Inc.
Drug Development Research
Volume 75, Issue 7, pages 438–448, November 2014
How to Cite
Morado-Urbina, C. E., Alvarado-Vázquez, P. A., Montiel-Ruiz, R. M., Acosta-González, R. I., Castañeda-Corral, G. and Jiménez-Andrade, J. M. (2014), Early, Middle, or Late Administration of Zoledronate Alleviates Spontaneous Nociceptive Behavior and Restores Functional Outcomes in a Mouse Model of CFA-Induced Arthritis. Drug Dev. Res., 75: 438–448. doi: 10.1002/ddr.21183
The authors have no competing interests.
- Issue published online: 21 OCT 2014
- Article first published online: 9 JUL 2014
- Manuscript Accepted: 6 JUN 2014
- Manuscript Received: 21 MAY 2014
- PROMEP. Grant Number: 103.5/12/3430
- arthritic pain;
- functional outcomes;
- late treatment
This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities.