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Presynaptic inhibition of primary afferent terminals is a powerful mechanism for controlling sensory information flow into the spinal cord. Lamina I is the major spinal nociceptive projecting area and monosynaptic input from C-fibers to this region represents a direct pathway for transmitting pain signals to supraspinal centers. Here we used an isolated spinal cord preparation to show that this pathway is under control of the afferent-driven GABAergic presynaptic inhibition. Presynaptic inhibition of C-fiber input to lamina I projection