Limited Changes in Spinal Lamina I Dorsal Horn Neurons following the Cytotoxic Ablation of Non-Peptidergic C-Fibers

Abeer W. Saeed, Sophie A. Pawlowski, Alfredo Ribeiro-da-Silva

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. 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. 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.