Intraarticular slow-release triamcinolone acetate reduces allodynia in an experimental mouse knee osteoarthritis model

摘要

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 1 beta. TCA 40 mu g 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 40 mu g also produced relief from mechanical allodynia for a few days compared to PBS control injections (P = 0.001). However, TCA 100 mu g in 5% hyaluronic acid produced relief from mechanical allodynia for at least 28 days compared to PBS control or 5% hyaluronic acid vehicle injections (P = 0.0005). Furthermore, TCA significantly suppressed expression of pain mediators induced by interleukin 1 beta 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. (C) 2016 Elsevier B.V. All rights reserved.