Nociceptive stimuli given to the periphery produce action potentials in the peripheral terminals of primary-afferent fibers and these electrical activities are transmitted through primary-afferent fibers to the spinal dorsal horn. Such nociceptive transmission is modulated by the actions of various receptors expressed in the peripheral and central terminals of primary-afferent fibers and in the spinal dorsal horn. Among the receptors, there are proteinase-activated receptors (PARs) which have a unique activation mechanism in that a proteolytically-exposed N-terminal region acts as a tethered ligand. This ligand binds to a site on the receptor itself, which results in triggering a signal transduction cascade. This review article will mention how the activation of the PARs modulates nociceptive transmission in the spinal dorsal horn.
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