Limited changes in spinal lamina I dorsal horn neurons following the cytotoxic ablation of non-peptidergic C-fibers

Mol Pain. 2015 Sep 9:11:54. doi: 10.1186/s12990-015-0060-z.

Abstract

Background: Non-peptidergic nociceptive neurons are a sub-population of small diameter primary sensory neurons that comprise approximately 50 % of the C fiber population. Together with the peptidergic sub-population, they transmit nociceptive information from the periphery to the superficial dorsal horn of the spinal cord. Despite the numerous studies investigating the role of the non-peptidergic primary afferents, their role in normal nociception and in pain remains poorly understood. Our lab has previously demonstrated that, in rat models of neuropathic and inflammatory pain, there is a de novo expression of substance P receptors (NK-1r) by lamina I pyramidal projection neurons, a neuronal population that normally does not express these receptors.

Results: In this study, we used a ribosomal toxin, saporin, conjugated to the lectin IB4 to selectively ablate the non-peptidergic nociceptive C fibers, to investigate if the loss of these fibers was enough to induce a change in NK-1r expression by lamina I projection neurons. IB4-saporin treatment led to the permanent ablation of the IB4-positive afferents but also to a small non-significant reduction in CGRP-positive afferents. An overall increase in immunoreactivity for the NK-1r was observed in lamina I projection neurons, however, the lack of non-peptidergic afferents did not increase the number of lamina I pyramidal projection neurons immunoreactive for the receptor.

Conclusions: Our results demonstrate that the deletion of the non-peptidergic afferents, at the L4-L5 spinal levels, is not sufficient to trigger the de novo expression of NK-1r by projection pyramidal neurons but increases the expression of NK-1r in fusiform and multipolar projection neurons. Furthermore, our data suggest that a neuropathic component is essential to trigger the expression of NK-1r by pyramidal neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Injections
  • Lectins / administration & dosage
  • Lectins / pharmacology
  • Male
  • Microscopy, Confocal
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / metabolism*
  • Peptides / metabolism*
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Rats, Sprague-Dawley
  • Ribosome Inactivating Proteins, Type 1 / administration & dosage
  • Ribosome Inactivating Proteins, Type 1 / pharmacology
  • Saporins

Substances

  • IB4-saporin conjugate
  • Lectins
  • Peptides
  • Ribosome Inactivating Proteins, Type 1
  • Saporins