title: Intraarticular slow-release triamcinolone acetate reduces allodynia in an experimental mouse knee osteoarthritis model.
abstract: Intraarticular steroid injection has been the mainstay of short-term treatment of knee osteoarthritis (OA) pain. However, the duration of therapeutic effect from a single injection is not as long as desired. In this study we use a viscous formulation of triamcinolone acetate (TCA) in hyaluronic acid to prolong the anti-allodynia effect of that steroid. OA was induced in mice by a partial medial meniscectomy. Over time the animals' developed a mechanical allodynia in the injected leg. Mice were then given a single intraarticular injection of TCA in a short-acting DMSO formulation, or a standard commercial suspension, or the drug formulated in 5% hyaluronic acid for slow-release. Control injections in OA mice were PBS or 5% hyaluronic acid vehicle. Mechanical allodynia was then monitored over the therapeutic period. Organotypic spinal cord slices and DRG culture were performed to assess whether TCA attenuates expressions of pain mediators induced by interleukin 1β. TCA 40μg in a fast-releasing DMSO formulation produced relief from mechanical allodynia for a few days compared to PBS control injections (P=0.007). Similarly, the commercial suspension of TCA 40μg also produced relief from mechanical allodynia for a few days compared to PBS control injections (P=0.001). However, TCA 100μg in 5% hyaluronic acid produced relief from mechanical allodynia for at least 28days compared to PBS control or 5% hyaluronic acid vehicle injections (P=0.0005). Furthermore, TCA significantly suppressed expression of pain mediators induced by interleukin 1β in spinal cord and DRG organotypic culture. Intraarticular TCA in a sustained release formulation of viscous 5% hyaluronic acid will produce a long-term attenuation of mechanical allodynia in the OA knees of mice.
authors.affiliation: Department of Anesthesiology, Rush University Medical Center, Chicago, IL, United States. Electronic address: Jeffrey_kroin@rush.edu.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kroin
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL, United States.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Kc
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL, United States.
authors.forename: John L
authors.initials: JL
authors.lastname: Hamilton
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL, United States.
authors.forename: Vaskar
authors.initials: V
authors.lastname: Das
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.affiliation: TAK Biopharma, Copenhagen, Denmark.
authors.forename: Ole M
authors.initials: OM
authors.lastname: Dall
authors.affiliation: Albumedix (Novozymes), Cincinnati, OH, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Shelly
authors.affiliation: TAK Biopharma, Copenhagen, Denmark.
authors.forename: Todd
authors.initials: T
authors.lastname: Kenworth
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL, United States; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States; Department of Internal Medicine (Section of Rheumatology), Rush University Medical Center, Chicago, IL, United States; Department of Bioengineering, University of Illinois at Chicago, IL, United States; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, United States.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D003692:Delayed-Action Preparations; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D007270:Injections, Intra-Articular; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D020370:Osteoarthritis, Knee / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D014221:Triamcinolone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D003692:Delayed-Action Preparations; D014221:Triamcinolone; D004121:Dimethyl Sulfoxide
keywords: Allodynia; Hyaluronic acid; Pain; Triamcinolone acetate