title: Early, middle, or late administration of zoledronate alleviates spontaneous nociceptive behavior and restores functional outcomes in a mouse model of CFA-induced arthritis.
abstract: 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.
authors.affiliation: Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, México.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Morado-Urbina
authors.forename: Perla Abigail
authors.initials: PA
authors.lastname: Alvarado-Vázquez
authors.forename: Rosa Mariana
authors.initials: RM
authors.lastname: Montiel-Ruiz
authors.forename: Rosa Issel
authors.initials: RI
authors.lastname: Acosta-González
authors.forename: Gabriela
authors.initials: G
authors.lastname: Castañeda-Corral
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Jiménez-Andrade
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004487:Edema / Q000150:complications / Q000188:drug therapy; D005620:Freund's Adjuvant; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D059226:Nociceptive Pain / Q000150:complications* / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D005620:Freund's Adjuvant
keywords: arthritic pain; bisphosphonates; functional outcomes; late treatment