Cortical presynaptic control of dorsal horn C-afferents in the rat

PLoS One. 2013 Jul 30;8(7):e69063. doi: 10.1371/journal.pone.0069063. Print 2013.


Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C-fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C-fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C-fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C-fibers by means of GABAergic inhibitory interneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Stimulation
  • Evoked Potentials
  • Interneurons / physiology
  • Male
  • Motor Cortex / physiology*
  • Nerve Fibers, Unmyelinated / physiology*
  • Neural Pathways
  • Posterior Horn Cells / physiology*
  • Presynaptic Terminals / physiology*
  • Rats
  • Receptors, GABA-A / metabolism
  • Sciatic Nerve / physiology


  • Receptors, GABA-A

Grants and funding

Work was supported by CONACYT 176782 (GRP) and 164536 (MCL), PAPIIT IN202610 (GRP). YML and JPS received a scholarship from CONACyT (233849 and 245641). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.