Limited changes in spinal lamina I dorsal horn neurons following the cytotoxic ablation of non-peptidergic C-fibers.
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.
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC, H3G 1Y6, Canada. abeer.saeed@mail.mcgill.ca.|Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, H3A 0G1, Canada. abeer.saeed@mail.mcgill.ca.
Abeer W
AW
Saeed
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC, H3G 1Y6, Canada. sophie.pawlowski@mail.mcgill.ca.|Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, H3A 0G1, Canada. sophie.pawlowski@mail.mcgill.ca.
Sophie A
SA
Pawlowski
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC, H3G 1Y6, Canada. alfredo.ribeirodasilva@mcgill.ca.|Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, H3A 0G1, Canada. alfredo.ribeirodasilva@mcgill.ca.|Department of Anatomy and Cell Biology, McGill University, Montreal, QC, H3A 0C7, Canada. alfredo.ribeirodasilva@mcgill.ca.
Alfredo
A
Ribeiro-da-Silva
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D007267:Injections; D037102:Lectins / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000494:pharmacology; D000076985:Saporins
C496198:IB4-saporin conjugate; D037102:Lectins; D010455:Peptides; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins