Ketamine attenuates osteoarthritis of the knee via modulation of inflammatory responses in a rabbit model

Abstract

The aim of the present study was to investigate the efficacy of ketamine in attenuating osteoarthritis (OA) and modulating the expression of inflammatory mediators. A rabbit OA model was established by knee immobilization using plaster bandages. After six weeks, rabbits were randomly allocated into four groups (n=6/group): Normal saline, Ket60, Ket100, and Ket200 and twice a week for four weeks the rabbits received an intra-articular injection of saline, or 60, 100 or 200 µmol/l ketamine, respectively. One week after the final injection, samples of synovial membrane, synovial fluid and articular cartilage were isolated. The pathological changes were assessed by general observation, hematoxylin and eosin staining and Alcian blue/periodic-acid Schiff staining. Cartilage pathology was assessed using Mankin's scoring system. Tumor necrosis factor (TNF)-α and interleukin (IL)-10 levels in the synovial fluid were measured by enzyme-linked immunosorbent assays. The nuclear factor (NF)-κB p65 subunit expression level in cartilage samples was determined by immunohistochemistry. OA was characterized by morphological changes in the articular surface, cartilage lesions, infiltration of inflammatory cells and a significantly increased Mankin's score. Elevated TNF-α and reduced IL-10 levels in the synovial fluid, along with increased p65 expression levels in the cartilage were observed in OA rabbits. Intra-articular injection of ketamine ameliorated the pathological characteristics of OA, reduced the Mankin's score, decreased TNF-α and NF-κB p65 expression levels, and increased the level of IL-10 expression in a dose-dependent manner. Thus is was demonstrated that Ketamine suppresses the inflammatory response in OA by modulating inflammatory mediator expression levels in a rabbit model of OA.

Intravenous anesthetic ketamine attenuates complete Freund’s adjuvant-induced arthritis in rats via modulation of MAPKs/NF-κB

“…# P < 0.05, ## P < 0.01, significantly different as compared to control group; *P < 0.05, **P < 0.01, significantly different as compared to the AA group and IL-6 in AA rats. These results are found in accordance with earlier report where KET showed to reduce the level of TNF-α [13]. The transcription factor NF-κB has been well documented as a critical controller of inflammation in RA.…”

“…In recent report by Hanna et al [12], ketamine showed reduction in pain in rheumatoid arthritis patient with comorbid fibromyalgia. Moreover, ketamine also showed reduction of the Mankin's score, decreased TNF-α and NF-κB p65 expression levels, and increased the level of IL-10 expression in a concentration-dependent manner in a rabbit model of OA [13]. However, the mechanism by which ketamine ameliorates the RA has been poorly understood [14].…”

Ketamine for pain management

“…Ketamine has anti-inflammatory effects, modulating the production of different proinflammatory mediators. A recent study using a rabbit model of gonarthrosis found that ketamine suppressed the inflammatory response in osteoarthritis, 28 whereas a systematic review concluded that intraoperative ketamine reduces the postoperative IL-6 inflammatory response in surgical patients. 15 …”

Schmerztherapie beim Patienten mit Hufrehe

“…Darüber hinaus hat Ketamin entzündungshemmende Wirkungen, indem es die Produktion verschiedener proinflammatorischer Mediatoren moduliert. Eine kürzlich durchgeführte Studie in einem Kaninchenmodell für Gonarthrose ergab, dass Ketamin die Entzündungsreaktion bei Arthrose unterdrücken kann 36 , während eine systematische Überprüfung zu dem Schluss kam, dass intraoperatives Ketamin die postoperative IL-6-Entzündungsreaktion bei chirurgischen Patienten reduziert 37 .…”