A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

Mol Pain. 2014 Jan 17:10:3. doi: 10.1186/1744-8069-10-3.


Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents.

Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin.

Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholera Toxin / pharmacology
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Mechanotransduction, Cellular* / drug effects
  • Models, Neurological*
  • Myelin Sheath / metabolism
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / pathology
  • Vesicular Glutamate Transport Protein 1 / metabolism
  • Vesicular Glutamate Transport Protein 2 / metabolism


  • Slc17a6 protein, rat
  • Slc17a7 protein, rat
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Glutamate Transport Protein 2
  • Cholera Toxin