Primary afferent-driven presynaptic inhibition of C-fiber inputs to spinal lamina I neurons.

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 and local-circuit neurons is mediated by recruitment of Aβ-, Aδ- and C-afferents. C-fiber-driven inhibition of C-fibers functions as a feedforward mechanism, by which the homotypic afferents control sensory information flow into the spinal cord and regulate degree of the primary nociceptive afferent activation needed to excite the second order neurons. The presynaptic inhibition of C-fiber input to lamina I neurons may be mediated by both synaptic and non-synaptic mechanisms, and its occurrence and extent are quite heterogeneous. This heterogeneity is likely to be reflective of involvement of lamina I neurons in diverse circuitries processing specific modalities of sensory information in the superficial dorsal horn. Thus, our results implicate both low- and high-threshold afferents in the modulation of C-fiber input into the spinal cord.