The Role Of Silent Nociceptors In Inflammatory Knee Pain

Purpose: Osteoarthritis (OA) development is a complex process that is driven by a plethora of inflammatory mechanisms which disrupt normal cartilage homeostasis and thus trigger joint degeneration. Accordingly, a large proportion of OA patients present clinical signs of joint inflammation such as swelling and effusion in addition to the hallmark symptoms of OA: pain and functional disability. Concurrently, joint inflammation plays a crucial role in the development of OA-associated pain indicating important cross-talk between joint innervating nociceptive neurons and inflammatory mediators. Recently, we demonstrated in-vitro that the inflammatory mediator nerve growth factor (NGF) activates silent nociceptors (SN). SN are sensory afferents that are insensitive to noxious mechanical stimuli under normal conditions but become sensitized during inflammation. SN constitute between 30 - 50 % of all articular nociceptive afferents. The high abundance of silent afferents in deep somatic tissues together with their peculiar properties have fueled speculations about a prominent role in inflammatory pain ever since they had first been described more than 30 years ago, but hitherto, neither the molecular mechanism underlying their un-silencing, nor their exact role in pain signaling have been deciphered.Thus, the overall goal of this study was to examine the contribution of SN to the generation of inflammatory knee pain.