Hemokinin-1 as a Mediator of Arthritis-Related Pain via Direct Activation of Primary Sensory Neurons

The tachykinin hemokinin-1 (HK-1) is involved in immune cell development and inflammation, but little known about its function pain. It acts through the NK1 receptor, several effects are mediated by a yet unidentified target. Therefore, we investigated role mechanism of action HK-1 arthritis models distinct mechanisms with special emphasis on Arthritis was induced i.p. K/BxN serum (passive transfer inflammatory cytokines, autoantibodies), intra-articular mast tryptase or Complete Freund’s Adjuvant (CFA, active immunization) wild type, HK-1- NK1-deficient mice. Mechanical- heat hyperalgesia determined dynamic plantar esthesiometry increasing temperature hot plate, respectively, swelling measured plethysmometry micrometry were significantly reduced HK-1-deleted, not mice all models. serum-induced histopathological changes (day 14) also decreased, early myeloperoxidase activity detected luminescent vivo imaging increased HK-1-deleted similarly to CFA model. However, vasodilation plasma protein extravasation laser Speckle fluorescent imaging, altered deficiency any Ca 2+ -influx primary sensory neurons, which seen cells after pertussis toxin-pretreatment, extracellular -free medium. These first results showing that mediates arthritic pain cellular, vascular mechanisms, independently activation. activates neurons presumably via channel-linked receptor. Identifying target opens new directions understand joint leading novel therapeutic opportunities.