title: Intra-articular administration of an antibody against CSF-1 receptor reduces pain-related behaviors and inflammation in CFA-induced knee arthritis.
abstract: Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. CFA-injected mice were then treated twice weekly from day 10 until day 25 with anti-CSF-1R antibody (3 and 10 μg/5 μL per joint), isotype control (rat IgG 10 μg/5 μL per joint) or PBS (5 μl/joint). Knee edema, spontaneous flinching, vertical rearing and horizontal exploratory activity were assessed at different days. Additionally, counts of peripheral leukocytes and body weight were measured to evaluate general health status. Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA.
authors.affiliation: Unidad Académica Multidisciplinaria Reynosa-Aztlán, UAT, Reynosa, Tamaulipas, Mexico. Electronic address: abigail1049@gmail.com.
authors.forename: P A
authors.initials: PA
authors.lastname: Alvarado-Vazquez
authors.affiliation: Unidad Académica Multidisciplinaria Reynosa-Aztlán, UAT, Reynosa, Tamaulipas, Mexico. Electronic address: morado.ur@gmail.com.
authors.forename: C E
authors.initials: CE
authors.lastname: Morado-Urbina
authors.affiliation: Facultad de Medicina, UAEM, Cuernavaca, Morelos, Mexico. Electronic address: gabriela.castaneda@uaem.mx.
authors.forename: G
authors.initials: G
authors.lastname: Castañeda-Corral
authors.affiliation: Unidad Académica Multidisciplinaria Reynosa-Aztlán, UAT, Reynosa, Tamaulipas, Mexico. Electronic address: racosta@uat.edu.mx.
authors.forename: R I
authors.initials: RI
authors.lastname: Acosta-Gonzalez
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, Sendai, Japan. Electronic address: hkitaura@m.tohoku.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Kitaura
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, Sendai, Japan. Electronic address: k-kimura@dent.tohoku.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, Sendai, Japan. Electronic address: t-yamamo@m.tohoku.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Takano-Yamamoto
authors.affiliation: Unidad Académica Multidisciplinaria Reynosa-Aztlán, UAT, Reynosa, Tamaulipas, Mexico. Electronic address: jimenez.andrade1810@gmail.com.
authors.forename: J M
authors.initials: JM
authors.lastname: Jiménez-Andrade
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D005620:Freund's Adjuvant; D007249:Inflammation / Q000276:immunology; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008813:Mice, Inbred ICR; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D005620:Freund's Adjuvant; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: Arthritic pain; Intra-articular injection; Knee inflammation; c-Fms