Involvement of Nav 1.8 sodium ion channels in the transduction of mechanical pain in a rodent model of osteoarthritis

OA-like changes were induced in male Wistar rats by an intra-articular injection of 3 mg sodium monoiodoacetate (MIA). Joint nociception was measured at day 14 by recording electrophysiologically from knee joint primary afferents in response to non-noxious and noxious rotation of the joint both before and following close intra-arterial injection of A-803467. The effect of Nav1.8 blockade on joint pain perception and secondary allodynia were determined in MIA treated animals by hindlimb incapacitance and von Frey hair algesiometry respectively.A-803467 significantly reduced the firing rate of joint afferents during noxious rotation of the joint but had no effect during non-noxious rotation. In the pain studies, peripheral injection of A-803467 into OA knees attenuated hindlimb incapacitance and secondary allodynia.These studies show for the first time that the Nav1.8 sodium channel is part of the molecular machinery involved in mechanotransduction of joint pain. Targeting the Nav1.8 sodium channel on joint nociceptors could therefore be useful for the treatment of OA pain, avoiding the unwanted side effects of non-selective nerve blocks.Osteoarthritis (OA) is a musculoskeletal disorder in which joint degeneration leads to a loss of mobility and function. OA primarily affects the weight bearing joints (for example knees, hips) and is typified by synovitis and degeneration of the articular cartilage and subchondral bone. The most prominent feature but least understood aspect of OA is joint pain which typically worsens with weight bearing and activity. The clinical diagnosis and treatment of OA pain has proven to be a difficult challenge because of the multitude of complex underlying mechanisms and the fact that different patients show a varied response to the same therapy. The preferred first line treatment for OA pain is non-steroidal anti-inflammatory drugs; however, the beneficial outcome of these drugs is limited and some patients fail to achieve any pain relief at