TRAUMEEL® PRODUCT MONOGRAPH14

of AEs,[Rutjes 2012] while a network analysis comparing the relative efficacy of treatments for knee OA concluded that IA HA was more effective than oral NSAIDs (except diclofenac), probably due to a beneficial effect of the IA procedure itself.[Bannaru 2015]

Role of inflammation OA is a multifactorial, degenerative joint disorder, with some key pathophysiological aspects playing central roles.[Thysen 2015] The effects of sub-clinical chronic inflammation in OA are now increasingly being recognized.[Bonnet 2005] In the development of OA, pro-inflammatory cytokines have been shown to be associated with cartilage damage.[Haseeb 2013, Malemud 2010, Fernandes 2002] Chronic inflammation develops over a longer period of time and may persist for weeks, months or years. Markers of chronic inflammation, such as C-reactive protein (CRP), may be elevated in patients with OA, and may be mediated by IL-6, which is the major cytokine secreted by macrophages. [Pearle 2007] IL-6 may also play a role in angiogenesis, which is another factor contributing to the pathology of OA.[Walsh 2001, Mentlein 2005]

Several enzymes, e.g., cyclo-oxygenase (COX) and lipoxygenase (LOX) are catalysts for reactions, producing mediators of inflammation and pain. COX enzymes are responsible for the production of lipid mediators, including prostaglandins, prostacyclin and thromboxanes (Figure 1). LOX enzymes are responsible for the production of leukotrienes, which are lipid signalling molecules synthesized from arachidonic acid. An example is LTB4 which is synthesized by the 5-LOX enzyme. This is a powerful chemo-attractant for leukocytes,[Haeggstrom 2004] and is implicated in the pathogenesis of inflammation.

Figure 1 Lipoxygenase (LOX) and cyclooxygenase (COX) enzymes synthesize mediators involved in inflammation and pain

Arachidonic Acid

COX-2

Prostaglandin E2

COX-1

Thromboxane A2

Abnormal Platelet Aggregation

5-Lipoxygenase

Leukotriene B4

Inflammation and Joint Destruction

Along with their roles in the pathogenesis of inflammation, the presence of inflammatory mediators, such as prostaglandins and leukotrienes, in the osteoarthritic joint lowers the threshold of pain, resulting in heightened pain sensations.[Adatia 2012]